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HIV Transmission Prevention 

HIV Transmission Prevention
Chapter:
HIV Transmission Prevention
Author(s):

Carolyn Chu

and Christopher M. Bositis

DOI:
10.1093/med/9780190493097.003.0004
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date: 12 December 2017

Introduction

Similar to combination HIV treatment using multiple medications alongside other interventions, multifaceted approaches to HIV prevention are required to effectively reduce transmission risk. Prevention strategies encompass a broad range of specific behavioral, structural, and biomedical interventions, and high-quality evidence exists for many of these approaches. HIV pre-exposure prophylaxis has been recently introduced as a new clinical tool. Other novel agents and interventions continue to be investigated and may significantly improve the ability to prevent HIV transmission and acquisition in the near future. Nevertheless, there are still considerable challenges in motivating fundamental individual- and community-level behaviors and overcoming structural obstacles that affect access to prevention resources. These need to be sustainably addressed in order to successfully reduce the global burden of HIV (Figure 4.1).


Figure 4.1 Component prevention interventions to promote engagement in care and optimal outcomes for HIV-positive and HIV-negative populations.

Figure 4.1 Component prevention interventions to promote engagement in care and optimal outcomes for HIV-positive and HIV-negative populations.

source: Treatment Action Group.

Behavioral Interventions

Behavioral interventions to prevent HIV transmission include both general educational campaigns about sexual health, drug use, and risk reduction and specific messages tailored to special at-risk populations and individuals known to be HIV positive (“prevention with positives”). Condom promotion and skills training and condom distribution services have been mainstays for many sex education and HIV prevention programs. Others have encouraged sexual abstinence or monogamy and fidelity. Studies estimate that condoms reduce HIV transmission by greater than 70% when used consistently by serodiscordant heterosexual partners and men who have sex with men (MSM) (Giannou, 2015; Smith, 2015; Weller, 2002). A growing body of research also cites sexual partnering practices such as partner concurrency and age-discrepant partnering as underrecognized drivers of HIV risk, particularly in specific communities (Adimora, 2014; Anema, 2013; Harrison, 2008). Although in theory such harm reduction strategies should prevent infection, in practice each carries a different and uncertain level of risk due to a range of biological and contextual factors (Wei, 2011), including a low rate of accurate HIV status representation between partners.

Adolescents and adult women may be especially vulnerable to transmission not only from sociocultural factors (e.g., sexual coercion and violence, partner alcohol/drug use, and difficulty negotiating condom use) but also from biological factors such as mucosal and immunological features unique to the female genital tract (Kaushic, 2010). Behavioral interventions targeted to young people have attempted to reduce HIV risk by delaying sexual debut, promoting consistent condom use, and reducing partner concurrency and/or changes. Methods include school-based and/or peer-led approaches as well as novel cash transfer programs (to increase financial independence) and social media campaigns to reduce stigma and discrimination (Pettifor, 2013). Similarly, interventions targeted to at-risk women have used group-based, skills training sessions focused on healthy decision-making and mental wellness, aiming to empower women to build balanced relationships free of harmful power dynamics. Older adults are another population requiring unique consideration. Many exhibit risk behaviors similar to those of younger people, but they may be less knowledgeable about HIV, less likely to use condoms, more isolated from their peers, and less inclined to discuss risky activities with a health care provider. Age-related physiologic changes such as decreased vaginal lubrication and vaginal epithelial thinning can put older, postmenopausal women at especially high risk. Older men using erectile dysfunction medications may also demonstrate increased capacity for risky sexual activities. (Brooks, 2012). Older adults are more likely to be diagnosed with HIV infection late in the course of disease. One study found that median CD4+ T cell counts at first presentation to care were consistently lower for persons aged 50 years or older compared to younger adults by approximately 15% and that a greater proportion of older adults had an AIDS-defining diagnosis at or within 3 months of initial presentation (Althoff, 2010). Therefore, provider awareness and HIV testing are especially important for this often-overlooked population. The Centers for Disease Control and Prevention (CDC) currently maintains the Compendium of Evidence-Based Interventions and Best Practices for HIV Prevention, which includes more than 80 HIV risk reduction behavioral interventions at the individual, couple, group, and community levels; several are tailored for specific HIV risk categories (e.g., people who inject drugs and heterosexual adults), by race/ethnicity, and by sex. Many interventions are rooted in the “health belief model,” one of several social psychological frameworks used to develop behavioral interventions (Bonell, 2001; Kaufman, 2014). Despite a growing number of evidence-based strategies, one group that remains critically understudied is transgender populations. Transgender communities experience some of the highest rates of HIV infection globally, with prevalence estimates range from 8% to 68%. (World Health Organization, 2011), but relatively little data have accumulated on effective prevention options. Transgender female sex workers in particular face unique structural, interpersonal, and individual vulnerabilities that contribute to an extremely high level of HIV risk. Providers should be sensitive to a person’s gender identity and avoid making assumptions about sexual orientation and behavior based solely on identity because there is great diversity in this population. Targeted prevention approaches that acknowledge and respond to specific individual needs while empowering transgender communities to take a principal role in addressing population-level, structural concerns may be the most effective. Finally, many behavioral interventions emphasize regular HIV and sexually transmitted infections (STIs) screening as a cornerstone of prevention for all. Widespread efforts to expand HIV counseling and testing can help decrease HIV transmission risk by (1) ensuring that people living with HIV (PLWH) know their status, (2) supporting safe disclosure to sexual partners, (3) encouraging increased condom use, and (4) assisting with linkage to HIV care.

During the past several years, accumulating evidence has shown that PLWH are central to HIV prevention. Effective interventions targeting PLWH are likely to have a greater and more immediate impact on reducing HIV incidence than changing the behaviors of millions of people who are negative but at risk (CDC, 2014). These “prevention with positives” efforts are often built around the HIV care continuum and include discrete goals such as improving linkage to (and retention in) quality HIV care, initiating early antiretroviral therapy, screening for and treating concurrent STIs, addressing mental health and substance use, providing family planning and partner notification counseling, and achieving durable virologic suppression (Figure 4.2).


Figure 4.2 Conceptual framework of “prevention with positives” showing select goals, interventions, and outcomes.

Figure 4.2 Conceptual framework of “prevention with positives” showing select goals, interventions, and outcomes.

source: WHO.

Recommended Reading

Centers for Disease Control and Prevention. High-impact HIV prevention: CDC’s approach to reducing HIV infections in the United States. Available at http://www.cdc.gov/hiv/library/reports/index.html.

Centers for Disease Control and Prevention. HIV prevention in the United States: At a critical crossroads. Available at http://www.cdc.gov/hiv/library/reports/index.html.

Kaufman M, Cornish F, Zimmerman RS, et al. Health behavior change models for HIV prevention and AIDS care: Practical recommendations for a multi-level approach. J Acquir Immune Defic Syndr. 2014; 66(Suppl. 3):S250–S258.Find this resource:

Structural and Systems-Level Interventions

Safety of the Blood Supply

Multiple organizations throughout the United States (e.g., the American Red Cross and hospital and community blood banks) contribute to population-level and local procurement and donation of blood products. Establishments that collect and process blood are ultimately responsible for individual product safety. However, the US Food and Drug Administration (FDA) is responsible for regulating how donations are collected and blood is transfused. It does so by ensuring transfusion recipients are protected through multiple, overlapping safeguards. These specific measures encompass five main “layers” of safety: (1) donor screening for diseases that could be transmitted via transfusion; (2) approval of all testing platforms that evaluate donated blood for infections, including HIV and viral hepatitis; (3) quarantine of donated specimens until testing verifies suitability; (4) donor deferral registries; and (5) required reporting and subsequent investigations and corrective actions when product deviations occur. The FDA also regularly inspects collection centers to confirm that they are adhering to quality standards and best practices. In addition, the CDC plays a role in monitoring blood safety by assisting state and local health departments and hospitals in investigating reports of potential infectious disease transmission.

Widespread HIV-1 antibody screening of donated blood began in the United States in 1985. HIV-2 antibody screening was introduced in 1992. Since 1999, donations have also been pooled and tested for HIV-1 RNA. HIV RNA testing allows for the detection of acute HIV infection because antibodies to HIV typically do not develop until approximately 3 weeks after HIV acquisition. By incorporating HIV-1 RNA testing into the routine evaluation of donated blood products, centers are able to identify donors who might have been recently infected (Busch, 2003; Kleinman, 2009). As a result of these various improvements in screening and testing practices, the modeled risk for HIV infection from transfusion of blood products in the United States declined from 1 in 450,000–600,000 donations in 1995 to 1 in 2,135,000 donations from in 2001. The most recent population-based estimate of the risk for acquiring HIV infection through US blood transfusion is 1 in 1,467,000 (Zou, 2010). In 2010, a description of the most recent reported case of transfusion-transmitted HIV infection was published: This was the first reported occurrence since 2002 (CDC, 2010).

Prevention of HIV Related to Injection Drug Use

Injection drug use has long been associated with HIV transmission. Despite a decrease in the overall number of HIV infections due to IDU, recent CDC estimates indicate that less than 10% of new infections in the United States are attributed to IDU (CDC, 2015). It remains an important transmission risk factor worldwide. Equipment used for injecting can be an effective vector for spreading virus. Blood is often drawn back into the needle and syringe pre- and post-injection; therefore, equipment recently used on an HIV-positive individual can contain a considerable amount of blood that contains HIV. Although HIV generally degrades quickly outside the body under certain conditions, studies indicate it can survive for longer periods of time (up to 6 weeks) within a sealed syringe (Heimer, 2000). Higher levels of HIV present in the blood injected, larger volume of injected blood, and/or higher injection frequency may increase risk of transmission. Estimates of infection risk from IDU on a per-act basis range from 0.63% to 2.4% (Baggaley, 2006). In addition to direct sharing of needles/syringes, various drug preparation practices can “indirectly” lead to HIV transmission, including sharing water used to flush blood out of a needle/syringe, reusing filters, and sharing other equipment that has not been sufficiently disinfected. Finally, although HIV risk has been demonstrated most clearly for intravenous administration of illicit substances, any parenteral exposure to unsterilized equipment can potentially lead to transmission (this includes subcutaneous and intramuscular injections), and HIV infections have been associated with injection of prescription medications, namely opioids.

Prevention of IDU-related HIV transmission has recently re-emerged as a public health priority for various reasons, including local outbreaks of HIV attributed to IDU in communities previously thought to be low prevalence areas (rural Indiana, Kentucky, and West Virginia). Many experts believe a “one size fits all” public health prevention strategy will not be fully effective, and they advocate for a multifaceted approach including (1) broad access to needle exchange and other harm reduction-oriented programs, (2) improved screening and recognition of substance use along with widespread HIV testing, and (3) expanded access to health services and providers who offer medications (i.e., opioid agonists) and other therapies that help mitigate the negative clinical consequences associated with IDU (Strathdee, 2015).

Harm Reduction Approaches to IDU and HIV Prevention

Harm reduction is a concept whereby programs and providers prioritize the prevention or reduction of adverse effects associated with certain behaviors over absolute cessation of the behavior. As applied to substance use (specifically IDU), harm reduction values minimizing substance-related impairment as much as, if not more than, eliminating substance use itself. Since the early 1990s, multiple harm reduction strategies—both biomedical and non-biomedical—have demonstrated effectiveness at decreasing IDU-related HIV transmission risk. Studies have specifically evaluated needle and syringe exchange programs (NSEPs), peer-based education and outreach, opioid substitution therapies, and both pre- and post-exposure prophylaxis (see sections on pre- and post-exposure prophylaxis) (Abdul-Quader, 2013; Aspinall, 2014; Garfein, 2007; MacArthur, 2012; Medley, 2009). NSEPs provide new needles/syringes, generally at no cost, in exchange for used equipment. Programs sometimes also distribute items such as alcohol swabs, sterile water/saline, mixing vessels, filters, and condoms. Other distribution models have been employed, including pharmacy sales and vending machines (MacArthur, 2014). In 2004, the World Health Organization (WHO) published an extensive report, concluding “there is compelling evidence that increasing the availability and utilization of sterile injecting equipment … reduces HIV infection substantially” and is cost-effective (WHO, 2004). Since then, evaluations from multiple agencies, such as the Institute of Medicine (IOM) and US Department of Health and Human Services/CDC, have also supported NSEPs as an integral, evidence-based component of comprehensive HIV prevention (CDC, 2012; IOM, 2007). Another non-biomedical prevention strategy, outreach and education, offers basic HIV education and risk reduction counseling; training on safer injecting and sexual practices; overdose prevention education and training (sometimes with naloxone distribution); counseling regarding drug treatment; and, occasionally, drug treatment referrals. Peer-driven and community-based models are particularly effective at engaging difficult to reach populations. They have successfully led to behavior changes such as decreased drug use, reduced equipment sharing, increased condom use, increased HIV testing, and increased enrollment in drug treatment (Garfein, 2007; Latkin, 2009; Medley, 2009; Needle, 2005). Research has also suggested that medically supervised, safer injection facilities are feasible and can play a meaningful role in reducing harms associated with HIV infection among people who inject drugs (PWID) (Kerr, 2007).

Substance Use Screening and Expanded HIV Testing

Screening, brief intervention, and referral to treatment (SBIRT) is a widely adopted public health approach to early identification and delivery of services for people with certain risky health behaviors. Although its effectiveness in reducing alcohol misuse and smoking has been verified, findings on its application to other substances have not been conclusive (Saitz, 2014). In 2008, the US Preventive Services Task Force (USPSTF) stated that evidence is “insufficient to assess the balance of benefits and harms of screening … for illicit drug use.” Nevertheless, some proponents cite a growing body of supporting evidence (Agerwala, 2012; Humeniuk, 2008; Substance Abuse and Mental Health Services Administration, 2011) and encourage continued efforts to identify optimal approaches for widespread SBIRT implementation in clinical practice.

Since 2006, the CDC has recommended that PWID be screened for HIV at least annually because some studies estimate that greater than 15% of HIV-positive PWID do not know their status (Branson, 2006; Chen 2012). HIV-positive PWID also tend to have lower rates of retention in care and virologic suppression compared to other risk groups (Celentano, 2007; Lourenco, 2014), highlighting important health disparities and opportunities. A recent report describing IDU participants in the National HIV Behavioral Surveillance System indicated that a majority had been tested for HIV at some point in their lifetime, but only half had undergone testing during the previous 12 months (Spiller, 2015). Interventions (including public health campaigns) that can reinforce the importance of regular screening and facilitate timely disclosure of results (i.e., rapid HIV testing) play key roles in identifying and linking HIV-positive PWID with care. Testing can also help prevent additional transmissions because HIV-positive individuals who know their status are significantly more likely to reduce risky behaviors in order to protect HIV-negative contacts (Marks, 2005). Furthermore, testing integrated with services that already focus on PWID—for example, NSEPs—offers a community-based, patient-centered alternative to testing at traditional medical facilities (Heimer, 2007; Strathdee, 2012).

Medical Management of IDU and HIV Prevention

Treatment of substance use, particularly IDU, can be challenging. It often requires a comprehensive, coordinated approach of multiple-component interventions across various dimensions: behavioral, psychological, social, and biomedical. Despite these complexities, multiple biomedical (i.e., pharmacologic) therapies have proven their role in reducing IDU and the subsequent transmission of HIV (MacArthur, 2012; Metzger, 2010; Vlahov, 2010). Opioids continue to be the most commonly injected drugs, and a number of medications are now available to manage opioid dependence, including both agonists (also referred to as opioid substitution therapies (OST)) and antagonists. Methadone, an opioid agonist, is the most widely used agent internationally. In the United States, it has been the mainstay of OST for decades and is available from licensed treatment programs that have attained special accreditation and are highly regulated. Buprenorphine, a partial opioid agonist, can be offered from a broader variety of settings (including primary care facilities), but trained prescribers must obtain special education and designation from the Drug Enforcement Administration. With buprenorphine, patients can be seen in practices not specifically identified as substance use treatment centers. This may help offset some of the stigma surrounding drug use and its treatment. Naltrexone (an opioid antagonist) is used mainly in relapse prevention, often subsequent to detoxification. Naloxone is another opioid antagonist and is commonly used to reverse the effects of opioids, especially in overdose. It is distributed as a co-formulation with buprenorphine to reduce potential for buprenorphine abuse. For HIV-positive PWID, effective treatment for drug use improves adherence to antiretroviral therapy and leads to sustained viral suppression, which then helps reduce the risk of forward transmission to uninfected partners (Metzger, 2010). Recent work also suggests that combined OST and antiretroviral therapy may yield the best clinical outcomes compared to either intervention alone (Nosyk, 2015).

In addition to heroin and other opioids, other substances are frequently injected and have been implicated in HIV transmission. Crystal methamphetamine (CM) in particular is a highly addictive stimulant that increases sexual arousal while also decreasing social inhibitions. Similar to cocaine, people who use CM are at risk not only through sharing equipment but also via certain sexual practices (e.g., engaging in unprotected and/or transactional sex and having multiple partners) that increase the likelihood of HIV transmission or acquisition. Although CM use and subsequent HIV risk have been mostly associated with MSM, the population of CM users is very diverse, and novel approaches to treatment and HIV prevention are needed to address multiple complexities surrounding its use (Degenhardt, 2010; HRSA, 2009).

Legal Considerations Surrounding HIV Prevention with IDU

As stated in the WHO’s 2004 report, “HIV infection among [PWID] is more likely to occur in legal environments where sterile injection equipment is more severely restricted.” Public facilitation of access to sterile equipment has faced significant controversy from law enforcement agencies and policymakers for decades. Historically, the United States has had among the most severe restrictions of any country. Use of federal funds for NSEPs was banned in 1988, lifted in 2009, and reinstated in 2011. Lack of a central funding mechanism has thus hampered scale up of NSEPs in the United States, and programs are largely funded through a mix of state and local government monies with some additional support by private donations. At the state level, some laws expressly prohibit possessing injection equipment, whereas others require a physician’s prescription for purchase. In areas where carrying used needles/syringes could be a prosecutable offense, PWID are often disincentivized from utilizing NSEPs despite their availability (for fear of arrest outside programs). Individual programs also represent a broad spectrum of structure and access: They can be fixed or mobile, with highly variable hours of operation. As of April 2015, 16 states and the District of Columbia explicitly authorized syringe exchange programs. A number of other states have laws that either decrease barriers to clean needle distribution or remove syringes altogether from the list of drug paraphernalia (Law Atlas, 2015). In states such as Connecticut and New York where restrictions on syringe access were repealed, some encouraging trends have been noted: Equipment sales through pharmacies have increased, self-reported needle-sharing has declined, and HIV incidence and prevalence have also declined (WHO, 2004).

In addition to the existence of drug control laws, enforcement of these laws influences individual behaviors, community stigma surrounding IDU, and the overall risk environment for PWID. In areas and situations perceived to be threatening, PWID may respond in ways that actually increase risk of acquiring or transmitting HIV—for example, injecting in a hurried manner, visiting unsupervised “shooting galleries,” and improperly disposing of used equipment that can then be picked up and used by someone else (Burris, 2011). Although PWID might try to balance risks and opportunities associated with obtaining new equipment, multiple economic, sociocultural, and political/regulatory limitations in the local environment undoubtedly shape decision-making and subsequently influence people’s actions.

Additional Structural and Systems-Level Considerations

In order to design feasible prevention interventions at the systems level, several other structural factors have been evaluated to determine how they affect HIV risk. These factors represent an extensive landscape of physical, economic, sociocultural, policy, and organizational dynamics. Physical factors such as proximity to—and convenience of—HIV services can play important roles in determining whether an individual is motivated to seek health care. Settings that offer co-located services (e.g., prevention counseling with STI/HIV testing and additional on-site medical care) and across expanded hours can be especially effective at linking people to, and retaining them in, quality care (Rothman, 2007). Stable housing and safety of the local community are other extremely important physical determinants of health and HIV risk. Many studies have found that unsafe and inadequate housing are significant barriers to receiving quality care and also increase risk of forward transmission (Aidala, 2015; Garcia 2015). In addition to specific substance use-associated HIV risks detailed previously, the intersections between behavioral/mental health and HIV have been well described (HRSA, 2015; Sikkema, 2010). Integrating behavioral and mental health services into prevention and treatment programs may help ensure coordinated delivery of comprehensive care for vulnerable populations. If possible, providers should elicit a thorough mental health history as well as screen for prior/current trauma and violence when caring for at-risk and HIV-positive individuals, and they should be able to do so in a sensitive manner. Clinicians should also approach substance use and sexual practices in a patient-centered, nonjudgmental manner in order to counsel effectively on HIV prevention and testing.

Economic factors are closely intertwined with HIV: A disproportionate burden of disease exists in less developed countries and among resource-limited communities. Such discrepancies directly and indirectly involve poverty and gender inequality, economic instability, labor migration, access to education and health resources, substance use, drug policies and enforcement, and so on (Zanakis, 2007). Low socioeconomic status has been linked to riskier health behaviors such as earlier initiation of sexual activity and less frequent condom use (Adler, 2006).

The epidemiology of incarceration closely reflects that of HIV. Many have cited socioeconomic marginalization as a common element that fuels these overlapping epidemics and results in correctional facilities bearing disproportionately high rates of HIV (National Minority AIDS Council and Housing Works, 2013). Challenges include lack of resources for testing and treatment in home communities as well as correctional facilities. Particularly in jails, rapid turnover of incarcerated individuals often limits widespread screening and evaluation.

Health insurance status is another economically related determinant affecting access to primary care and preventive services. Medical costs are prohibitive for the large number of people at risk for or living with HIV. In 2010, the Affordable Care Act (ACA) was signed into law. This had many significant HIV-related implications, including the following: (1) Individuals could not be denied coverage due to pre-existing health conditions including HIV, (2) states were given an option to expand Medicaid eligibility, (3) community health centers received increased support to provide HIV care, and (4) USPSTF-recommended HIV screening became reimbursable. Although it has been in effect for only a few years, early research predicts the ACA “may increase the number of people getting tested for HIV by nearly 500,000 by 2017” and that among people living with HIV who gain insurance through the ACA, the proportion of those unaware will decline by greater than 20% (Wagner, 2014). Even prior to the ACA, the majority of states (and the District of Columbia) already had public health HIV testing laws consistent with CDC testing recommendations, with many specific statutes encouraging HIV risk management and partner counseling/referral services in conjunction with testing.

Values and normative behaviors are shaped by sociocultural networks with which an individual identifies. They also often influence attitudes and beliefs regarding HIV risk. High levels of fear and lack of knowledge surrounding HIV, as well as negative perceptions/disapproval toward populations it most visibly affects, have propelled HIV-related stigma and discrimination since the 1980s. As a result, both PLWH and those at risk often feel isolated, becoming increasingly marginalized from family members, peers, and communities. Some individuals have also described negative experiences with health care providers (Anderson, 2009). Fear of stigma and discrimination continue to be major reasons why people are reluctant to discuss risky behaviors, get tested, and disclose their HIV status to social contacts as well as service providers (Valdiserri, 2002). One approach that multiple organizations have attempted is to expand public health awareness through large-scale, mass media campaigns (including social media) that foster greater knowledge of HIV/AIDS and improved attitudes and behaviors including testing. These and other efforts directed at health literacy aim to empower individuals and increase both self-efficacy and self-care behaviors. Community building and mobilization are other important components to scaling up prevention interventions because social networks play a key role in delivering peer-to-peer information and support (Latkin, 2013; Mahajan, 2008). Finally, antidiscrimination policies and laws such as the 2009 US repeal of the HIV travel and immigration ban (resulting from decades of advocacy and education) can help reduce HIV-related stigma and advance universal human rights. In jurisdictions in which same-sex relationships and/or transactional sex are criminalized, MSM and sex workers may feel less inclined to access condoms and/or present for HIV testing for fear of discrimination and legal punishment.

Recommended Reading

Busch MP, Kleinman SF, Nemo GJ. Current and emerging infectious risks of blood transfusions. JAMA. 2003; 289(8):959–962.Find this resource:

Metzger DS, Zhang Y. Drug treatment as HIV prevention: Expanding treatment options. Curr HIV/AIDS Rep. 2010; 7(4):220–225.Find this resource:

Strathdee SA, Shoptaw S, Dyer TP, et al.; Substance Use Scientific Committee of the HIV Prevention Trials Network. Towards combination HIV prevention for injection drug users: Addressing addictophobia, apathy and inattention. Curr Opin HIV AIDS. 2012; 7(4):320–325.Find this resource:

Medical Interventions for HIV Transmission Prevention

Introduction

Medical interventions used to prevent HIV transmission and acquisition among patients at risk include PrEP, oPEP and nPEP, STI screening and treatment, voluntary medical male circumcision, vertical transmission prevention, and treatment as prevention (TasP).

Pre-exposure Prophylaxis

PrEP is the use of antiretroviral medication before HIV exposure as a means to prevent HIV acquisition in at-risk, HIV-negative individuals. For the purposes of this section, PrEP should be understood to mean daily oral antiretroviral prophylaxis. Other routes and schedules (e.g., vaginal antiretroviral therapy (ART)-containing gel and intermittent PrEP) have been and/or are being studied but are discussed in the section Investigational Interventions.

Data: Clinical Trials and Real-World Effectiveness

Studies evaluating this strategy have found that, when taken consistently, PrEP is very effective at reducing the rate of HIV acquisition in those at highest risk, including MSM, transgender women who have sex with men, PWID, and coupled and single women and men engaging in heterosexual sex (see Table 4.1). Although the benefit varied slightly across the various studies, with reductions in the rate of HIV infection ranging from 44% to 75%, several common features should be highlighted. First, it was most effective among those who were most adherent. In the iPrEx study, for example, the relative risk of HIV infection was 92% lower among those with detectable levels of study drug compared to those without (Grant, 2010), and in the Bangkok Tenofovir study it was 70% lower (Choopanya, 2013). Furthermore, in the two negative PrEP trials to date, adherence was extremely poor (<30%) based on drug-level testing (Marrazzo, 2015; van Damme, 2012), again underscoring the importance of adherence for PrEP to be beneficial. Second, it was generally well tolerated, with fewer than 10% of patients reporting serious adverse events (US Public Health Service, 2014). Third, risk behaviors generally decreased during the study period; in both the iPrEx and the Partners PrEP studies, for example, the percentage of patients who reported unprotected intercourse decreased significantly during the study period (Baeten, 2012; Grant, 2010).

Table 4.1 Summary of Randomized, Controlled PrEP Trials

Trial

N, Study Population; Setting

Intervention

Effect—Hazard Ratio [Estimated Reduction in HIV Acquisition] (95% CI)

Reference

iPrEX

2499 MSM, transgender women, United States, South America, Thailand, South Africa

TDF/FTC

0.56 [44%] (15–63)

Grant (2010)

Partners PrEP

4747 heterosexual women and men; Kenya and Uganda

  • TDF

  • TDF/FTC

  • 0.33 [67%] (0.19–0.56)

  • 0.25 [75%] (0.13–0.45)

Baeten (2012)

TDF 2

1219 heterosexual women and men; Botswana

TDF/FTC

0.38 [62%] (0.22–0.83)

Thigpen (2012)

Thai IDU

2413 PWIDs; Thailand

TDF

0.51 [49%] (0.1–0.72)

Choopanya (2013)

FemPrEP

2120 heterosexual women; Africa

TDF/FTC

0.94 [6%] (0.59–1.52)

Van Damme (2012)

VOICE

5029 heterosexual women; Africa

  • TDF

  • TDF/FTC

  • 1.49 [–49%] (0.97–2.29)

  • 1.04 [–4%] (0.73–1.49)

Marrazzo (2015)

FTC, emtricitabine; MSM, men who have sex with men; PWID, people who inject drugs; TDF, tenofovir disoproxil fumarate.

Since the publication of these study data, the number of at-risk patients taking PrEP has increased substantially (Figure 4.3). Effectiveness of PrEP in the “real world” has not yet been studied exhaustively. However, data from the Kaiser group in San Francisco are highly encouraging: Among 657 PrEP initiators in an 18-month period, no new infections occurred during 388 person-years of follow-up, despite the fact that data from similar populations would predict an infection rate of 8.9/100 person-years—suggesting that as many as 34 new infections may have been averted through PrEP use (Volk, 2015). In addition, data from the PROUD study in the United Kingdom, which was designed to mimic real-world settings, showed a relative reduction in HIV incidence among MSM receiving PrEP of 86%, corresponding to a number needed to treat of just 13 in order to prevent 1 new HIV infection (McCormack, 2015).


Figure 4.3 Number of new PrEP starts over time.

Figure 4.3 Number of new PrEP starts over time.

source: Bush (2015).

Eligibility

According to the CDC’s 2014 guidelines, PrEP (using tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)) is recommended as a prevention option for adults at substantial risk of acquiring HIV infection, including MSM, heterosexually active women and men, and injection drug users (Table 4.2) (CDC, 2014). The guidelines do not define what constitutes a “high number” of sex partners, nor do they define what constitutes a “high prevalence area or network”; however, note that recent data from the National Health and Nutrition Examination Survey (NHANES) indicate that the lifetime prevalence of HIV is almost twice as high for individuals reporting 5–9 lifetime sexual partners, and nearly fivefold higher among those reporting 10 or more, compared to those reporting 4 or fewer (Woodring, 2015). Regarding the definition of “high prevalence,” the majority of PrEP studies were conducted in populations in which the background HIV incidence was at least 3 per 100 person-years, and the International Antiviral Society–USA panel therefore recommends PrEP for those in which the background incidence is greater than 2% (Marrazzo, 2014).

Table 4.2 Summary Guidelines for PrEP Use

Men Who Have Sex with Men

Heterosexually Active Women and Men

Injection Drug Users

Those at substantial risk of acquiring HIV

  • HIV-infected sexual partner

  • Recent bacterial STI

  • High number of sex partners

  • Inconsistent or no condom use

  • History of engaging in commercial sex work

  • HIV-infected sexual partner

  • Recent bacterial STI

  • High number of sex partners

  • Inconsistent or no condom use

  • History of engaging in commercial sex work

  • Being in a high-prevalence area or network

  • HIV-positive injecting partner

  • History of sharing injection equipment

  • History of recent drug treatment (but currently injecting)

Clinically eligible if

  • Documented negative HIV test

  • No signs/symptoms of acute HIV infection

  • Normal renal function (CrCl ≥60 ml/min)

  • No contraindicated medications

  • Documented hepatitis B virus infection and vaccination status

Prescription

  • TDF/FTC (FDC) once daily

  • No more than 3-month supply

Other services

  • Follow-up visits at least every 3 months to provide HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, and STI symptom assessment

  • At 3 months and every 6 months thereafter, assess renal function

  • Every 6 months, test for bacterial STIs

Do oral/rectal STI testing

Assess pregnancy intent; pregnancy test every 3 months

Access to clean needles/syringes and drug treatment services

FDC, fixed-dose combination; FTC, emtricitabine; STI, sexually transmitted infection; TDF, tenofovir disoproxil fumarate.

source: Adapted from CDC (2014).

The New York State Department of Health AIDS Institute also released PrEP guidelines in 2015 (New York State Department of Health, 2015). These guidelines define patients at substantial, ongoing risk for HIV acquisition as follows:

  • MSM who engage in unprotected anal intercourse

  • Individuals who are in a serodiscordant sexual relationship with a known HIV-infected partner

  • Male-to-female and female-to male transgender individuals engaging in high-risk sexual behaviors

  • Individuals engaging in transactional sex, such as sex for money, drugs, or housing

  • Injection drug users who report any of the following behaviors: sharing injection equipment (including to inject hormones among transgender individuals), injecting one or more times per day, injecting cocaine or methamphetamine, and engaging in high-risk sexual behaviors

  • Individuals who use stimulant drugs associated with high-risk behaviors, such as methamphetamine

  • Individuals diagnosed with at least one anogenital sexually transmitted infection in the past year

  • Individuals who have been prescribed nPEP who demonstrate continued high-risk behavior or have used multiple courses of nPEP

WHO recently released its updated guidelines on PrEP, which simply state that “oral PrEP containing TDF should be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination HIV prevention approaches” (WHO, 2015). WHO defines substantial risk as HIV incidence greater than 3 per 100 person-years in the absence of PrEP (WHO, 2015).

It is important to emphasize that PrEP should not be prescribed as a sole prevention intervention in those at risk but, rather, it should be part of a comprehensive HIV prevention plan, including behavioral and other prevention strategies.

How PrEP Should Be Prescribed

Prior to initiating PrEP in eligible patients, providers must document the following:

  • Absence of acute or chronic HIV infection

  • Normal renal function (CrCl ≥60 ml/min)

  • Hepatitis B immunity or infection and vaccination status

To document absence of acute or chronic HIV infection, the CDC recommends following the algorithm shown in Figure 4.4. Oral rapid HIV testing should not be used due to its lower sensitivity for detecting HIV compared to blood tests (CDC, 2014), and a negative (preferably fourth-generation) test result should be documented within the week before initiating PrEP. Additional testing, such as viral load testing, should also be done for anyone who reports signs or symptoms of acute HIV infection within the previous 4 weeks and for those with high-risk exposures within 4 weeks prior to initiating PrEP (CDC, 2014; New York State Department of Health, 2014).


Figure 4.4 Assessment for acute/chronic HIV infection prior to PrEP initiation.

Figure 4.4 Assessment for acute/chronic HIV infection prior to PrEP initiation.

source: CDC (2014).

Current CDC guidelines state that eligible patients meeting appropriate clinical criteria should receive tenofovir/emtricitabine (TDF 300 mg/FTC 200 mg) once daily. Whereas the CDC states that daily TDF alone may be given as an alternative to PWID and heterosexually active women and men, WHO lists daily TDF as the preferred PrEP regimen (CDC, 2014; WHO, 2015). The CDC recommends that patients be given no more than a 3-month supply of medications at one time. Recommended follow-up and testing for PrEP toxicity and comorbid conditions are detailed in Table 4.2.

PrEP Risks

PrEP has generally been very well tolerated in both clinical studies and real-world settings, with fewer than 10% of recipients experiencing serious adverse events (CDC, 2014). The most commonly reported side effects are gastrointestinal, such as nausea, flatulence, headache, and weight loss. Sometimes referred to as “startup syndrome,” most resolve within the first month of treatment and can usually be managed symptomatically with over-the-counter medications (CDC, 2014).

More serious potential PrEP toxicities include acute and/or chronic kidney injury and bone demineralization. Analyses from the iPrEX study indicate that PrEP recipients experience a small but statistically significant decline in creatinine clearance (CrCl) that is nonprogressive and reversible upon PrEP discontinuation (Solomon, 2014). Similarly, patients from the same study who received PrEP experienced a small but statistically significant decrease in bone mineral density (BMD) compared to those who received placebo. However, there was no increase in fracture risk, no one with low BMD, and observed decreases in vertebral BMD were reversible with PrEP discontinuation (Mulligan, 2015).

For patients who become infected with HIV while on PrEP, there has been concern about the possible development of drug resistance. To date, such resistance has been rare, and it has been primarily observed in patients who had acute seronegative HIV infection, underscoring the importance of screening patients for possible acute HIV before initiating PrEP (CDC, 2014). When it does occur, resistance mutations to FTC appear to be more common than those to TDF (Lehman, 2015).

Concern that PrEP use will lead to an increase in risky sexual behavior (“risk compensation”) so far has not been borne out in either clinical trial or “real-world” settings. In both the iPrEx and the Partners PrEP studies, the percentage of patients who reported having sex without a condom decreased during the study period (Baeten, 2012; Grant, 2010). “Real-world” data from the aforementioned Kaiser cohort and PROUD studies also failed to demonstrate evidence of risk compensation based on the number of reported sexual partners, condom use, and rates of STIs (McCormack, 2015; Volk, 2015). Last, while adherence to PrEP was greatest among those reporting condomless anal intercourse in the ATN 110 study, which is an open-label feasibility study in young MSM ages 18–22 years, overall rates of sexual risk behavior as measured by the number of male partners, instances of condomless receptive anal intercourse, and instances of condom breakage during receptive anal intercourse remained stable (Hosek, 2015).

For patients who are chronically infected with hepatitis B virus (HBV) as evidenced by a positive hepatitis B surface antigen (sAg) test, the CDC recommends evaluation by a clinician experienced in the treatment of chronic HBV. Such patients who are given PrEP should be counseled that there is a potential risk of a flare in their HBV infection should they abruptly discontinue TDF-containing PrEP, although this has not yet been reported in HBV-positive, HIV-negative patients (CDC, 2014; Grant, 2010).

Women of childbearing age who wish to become pregnant or breast-feed while taking PrEP should be counseled that the PrEP studies to date excluded women who were or who became pregnant; however, data from the Antiviral Pregnancy Registry demonstrate no evidence of harm to fetuses exposed to these medications (Antiretroviral Pregnancy Registry, 2015). Furthermore, it should be emphasized that HIV-uninfected women who wish to conceive with an HIV-infected partner are at increased risk for HIV acquisition, and current US perinatal guidelines permit the use of PrEP for such patients (US Department of Health and Human Services, 2015). Although data are limited, the use of PrEP during lactation appears to be safe (CDC, 2014).

Discontinuing PrEP

PrEP should be discontinued in patients who acquire HIV infection; experience unacceptable side effects or toxicities, including renal disease; are unable to adhere to the prescribed regimen or follow-up visit schedule; or change their risk status such that PrEP is no longer indicated (CDC, 2014; New York State Department of Health AIDS Institute, 2014). Patients who acquire HIV while taking PrEP should be initiated on combination ART based on genotypic testing results and in accordance with current HIV treatment guidelines.

Unanswered Questions

Although PrEP has clearly been shown to be beneficial in the appropriate settings, unanswered questions remain. It is not clear, for example, how long PrEP can be safely prescribed. The CDC guidelines state that it should not be given for life but, rather, only during times of highest risk of HIV acquisition; however, many PrEP-eligible patients can be expected to remain so for extended periods of their lives (CDC, 2014).

The role of “on-demand” PrEP has also not yet been elucidated. Although data from the IPERGAY study conducted in France demonstrated high rates of protection when taken before and after sex (Molina, 2015), this strategy was not as effective as daily PrEP among the US-based cohort of the HPTN 067/ADAPT trial (Mannheimer, 2015).

Last, the role of PrEP for patients in serodiscordant relationships in which the HIV-infected partner is on suppressive ART is not clear. Data from the HPTN 052 trial demonstrated that no linked transmissions occurred among couples when the infected partner was suppressed on ART (Cohen, 2015). However, concerns persist that HIV transmission may still be possible due to daily variations in viral load, as well as potential discordance between serum viral load and that in genital and rectal secretions (Hosein, 2011). In addition, HIV-negative patients in such relationships may have other partners whose HIV status is unknown or who are HIV infected but not yet on treatment. This possibility was highlighted by the fact that nearly 40% of transmissions in the HPTN 052 study were unlinked (i.e., they came from someone other than their identified serodiscordant partner) (Cohen, 2015). PrEP is likely to be beneficial for such patients.

Occupational and Non-occupational Post-exposure Prophylaxis

Ethical considerations prohibit the evaluation of either oPEP or nPEP using randomized controlled trials. The data to support its use largely derive from animal models, inference from postnatal prophylaxis studies, observational studies, and one retrospective case–control study that showed an 81% reduction in the risk of infection among health care workers who took zidovudine after exposure (Cardo, 1997; Lunding, 2015; Otten, 2000;Shih, 1991; Young, 2007).

oPEP

The use of ART to prevent transmission of HIV for health care personnel who experience a high-risk occupational exposure was first recommended in 1990, and the US Preventive Health Service released its most recent oPEP guidelines in 2013 (Kuhar, 2013).

The risk of HIV acquisition after exposure in the health care setting appears to be directly related to the size of the viral inoculum, which is in turn influenced by the stage of disease of the source patient, as well as the quantity of blood to which the worker was exposed (Kuhar, 2013).

Current guidelines emphasize the following:

  • The HIV status of the source patient should be determined whenever possible to guide the need for initiating and/or maintaining oPEP.

  • When indicated, it should be started as soon as possible, preferably within 72 hours from the time of exposure.

  • All oPEP regimens should include three antiretroviral medications and should be taken for 4 weeks (Table 4.3).

  • Expert consultation, with either local experts or through the national HIV Post-Exposure Prophylaxis Hotline, is recommended in certain situations (Table 4.4).

  • Close follow-up services, including counseling, repeat HIV testing, and monitoring for drug toxicity, should be provided. HIV follow-up testing should be done 6 weeks, 12 weeks, and 4 months (if using a fourth-generation combination HIV antibody–p24 antigen test) or 6 months after the exposure (Table 4.5).

Table 4.3 Recommended oPEP Regimens—All to Be Taken ×4 Weeks

Preferred regimen

NRTI backbone

Base

  • Truvada 1 PO daily

  • (TDF 300 mg/FTC 200 mg FDC)

Raltegravir 400 mg twice daily

Alternatives

One of following

With one of following

  • Tenofovir DF (Viread; TDF) + emtricitabine (Emtriva; FTC)

  • available as Truvada

  • or

  • Tenofovir DF (Viread; TDF) + lamivudine (Epivir; 3TC)

  • or

  • Zidovudine (Retrovir; ZDV; AZT) + lamivudine (Epivir; 3TC); available as Combivir

  • or

  • Zidovudine (Retrovir; ZDV; AZT) + emtricitabine (Emtriva; FTC)

  • Raltegravir (Isentress; RAL)

  • or

  • Darunavir (Prezista; DRV) + ritonavir (Norvir; RTV)

  • or

  • Etravirine (Intelence; ETR)

  • or

  • Rilpivirine (Edurant; RPV)

  • or

  • Atazanavir (Reyataz; ATV) + ritonavir (Norvir; RTV)

  • or

  • Lopinavir/ritonavir (Kaletra; LPV/RTV)

  • or

  • Tenofovir + emtricitabine + elvitegravir + cobicistat (TDF/FTC/EVG/cobi, Stribild)

FDC, fixed-dose combination; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate.

source: Adapted from Kuhar (2013).

Table 4.4 Situations in Which Expert Consultation for oPEP Is Recommended

Scenario

Comments

Delayed (i.e., later than 72 hours) exposure report

Interval after which benefits from PEP are undefined.

Unknown source (e.g., needle in sharps disposal container or laundry)

  • Use of PEP to be decided on a case-by-case basis.

  • Consider severity of exposure and epidemiologic likelihood of HIV exposure.

  • Do not test needles or other sharp instruments for HIV.

Known or suspected pregnancy in the exposed person

Provision of PEP should not be delayed while awaiting expert consultation.

Breast-feeding in the exposed person

Provision of PEP should not be delayed while awaiting expert consultation.

Known or suspected resistance of the source virus to antiretroviral agents

  • If source person’s virus is known or suspected to be resistant to one or more of the drugs considered for PEP, selection of drugs to which the source person’s virus is unlikely to be resistant is recommended.

  • Do not delay initiation of PEP while awaiting any results of resistance testing of the source person’s virus.

Toxicity of the initial PEP regimen

  • Symptoms (e.g., gastrointestinal symptoms and others) are often manageable without changing PEP regimen by prescribing antimotility or antiemetic agents.

  • Counseling and support for management of side effects is very important because symptoms are often exacerbated by anxiety.

Serious medical illness in the exposed person

Significant underlying illness (e.g., renal disease) or an exposed provider already taking multiple medications may increase the risk of drug toxicity and drug–drug interactions.

Expert consultation can be made with local experts or by calling the National Clinicians’ Post Exposure Prophylaxis Hotline (PEPline) at 1-888-448-4911

source: Adapted from Kuhar (2013).

Table 4.5 Recommended Follow-Up of Health Care Personnel Exposed to Known or Suspected HIV-Positive Sources

Time from Exposure

Recommended Services

Counseling

Testing

Baseline

Transmission prevention (condom use; avoidance of blood/tissue donation; avoid breast-feeding if possible)

HIV antibody testing (preferable fourth-generation combined antibody/p24 antigen test)

Possible drug toxicities

Complete blood count

Possible drug interactions

Liver function TESTS

Importance of adherence

Renal function tests

72 hours

Even if not taking PEP—to review additional information about exposure or the source patient if available

If on PEP

Transmission prevention (condom use; avoidance of blood/tissue donation; avoid breast-feeding if possible)

Possible drug toxicities

Possible drug interactions

Importance of adherence

2 weeks

Transmission prevention

Complete blood count

Possible drug toxicities

Liver function tests

Possible drug interactions

Renal function tests

Importance of adherence

6 weeks

Transmission prevention

HIV antibody testing (preferable fourth-generation combined antibody/p24 antigen test)

If fourth-generation HIV testing is used

4 months

HIV antibody testing (if negative, HIV infection is excluded)

If fourth-generation HIV testing is not used

12 weeks

Transmission prevention

HIV antibody testing

6 months

HIV antibody testing (if negative, HIV infection is excluded)

source: Adapted from Kuhar (2013).

It is also important to remember that health care workers who experience an occupational exposure should be screened for hepatitis B and C virus infections. All hepatitis B-susceptible individuals should initiate the hepatitis B vaccine series, and those exposed to a patient with known acute or active HBV should be given hepatitis B immune globulin as well. There is currently no effective prophylaxis for hepatitis C infection.

nPEP

The CDC’s most recent nPEP guidelines were published in 2016 (Dominguez, 2016). The New York State Department of Health AIDS Institute released comprehensive guidelines on the use of antiretroviral medications following non-occupational exposures, including for victims of sexual assault, in 2014 (New York State Department of Health, 2014). Key points from these guidelines include the following:

  • For sexual assault victims, important considerations before initiating PEP include whether or not a significant exposure occurred during the assault; whether the victim is ready and willing to complete a PEP regimen; and knowledge of the alleged assailant’s HIV status, although a lack thereof should not delay PEP initiation when warranted based on the nature of the exposure.

    • Exposure types warranting PEP include direct contact of the vagina, penis, anus, or mouth with the semen, vaginal fluids, or blood of the alleged assailant, with or without physical injury, tissue damage, or the presence of blood at the site of the assault; when broken skin or mucous membranes of the victim have been in contact with blood, semen, or vaginal fluids from the alleged assailant; and in cases of bites that result in visible blood.

    • Baseline HIV testing should be performed for the victim, as should a pregnancy test for female victims.

    • When indicated, PEP should be initiated within 2–36 hours after the exposure.

    • Prophylactic treatment to prevent gonorrheal and chlamydial infections should also be offered, as should emergency contraception for female victims.

  • For patients with other potential non-occupational exposures to HIV, determination of the level of risk from the exposure is critical; nPEP is generally only indicated for patients with higher risk exposures (Table 4.6). Other key points include the following:

    • HIV testing of the source patient should be performed when possible.

    • All exposed patients should have the following done at baseline: HIV testing, site-specific testing for gonorrhea and chlamydia, testing for syphilis, and pregnancy testing for women.

    • When indicated, PEP should be initiated within 2–36 hours after the exposure.

    • Risk-reduction counseling should also be provided, including referrals for mental health and/or substance use disorder treatment programs when indicated, as well as discussion of future PrEP use for individuals with ongoing risk behavior.

Table 4.6 Level of Risk Based on Exposure Type for Consideration of nPEP

High-risk exposures—nPEP should be recommended

  • Receptive and insertive vaginal or anal intercourse with a partner who is HIV positive, or when the partner’s HIV status is unknown

  • Needle sharing with a partner who is HIV positive, or when the partner’s HIV status is unknown

  • Injuries with exposure to blood or other potentially infected fluids from a source known to be HIV-infected or HIV status is unknown (including needle sticks with a hollow-bore needle, human bites, and accidents)

Lower risk exposures—require case-by-case evaluation for nPEP

  • Oral–vaginal contact (receptive and insertive)

  • Oral–anal contact (receptive and insertive)

  • Receptive penile–oral contact with or without ejaculation

  • Insertive penile–oral contact with or without ejaculation

  • Factors that increase risk (nPEP should be offered)

  • Source person is known to be HIV-infected with high viral load

  • An oral mucosa that is not intact (e.g., oral lesions, gingivitis, and wounds)

  • Blood exposure

  • Presence of genital ulcer disease or other sexually transmitted infections

Exposures that do not warrant nPEP

  • Kissing

  • Oral-to-oral contact without mucosal damage (mouth-to-mouth resuscitation)

  • Human bites not involving blood

  • Exposure to solid-bore needles or sharps not in recent contact with blood (e.g., tattoo needles and lancets)

  • Mutual masturbation without skin breakdown or blood exposure

source: Adapted from New York State Department of Health AIDS Institute (2014).

New York State’s recommended nPEP regimen is as follows:

Tenofovir 300 mg + emtricitabine 200 mg (Truvada) once daily

Plus

Raltegravir 400 mg twice daily or dolutegravir 50 mg once daily

For 28 days

As with patients who experience occupational exposures, those with non-occupational exposures should be screened for hepatitis B and C infections and be given appropriate treatment and follow-up as described previously.

Screening and Treatment for Sexually Transmitted Infections

The link between STIs and an increased risk for HIV transmission/acquisition has been established for some time. This is supported by both biologic plausibility (e.g., genital tract inflammation leading to increased viral shedding in infected partners and increased access of HIV to subepithelial target cells) and epidemiologic synergy (Mayer, 2011; Ward, 2010). However, multiple confounders have made it difficult to estimate just how much these contribute to increased risk, and STI treatment studies to date have failed to consistently demonstrate any reduction in HIV transmission (Mayer, 2011; Ward, 2010). The Mwanza study from Tanzania stands out as the one notable exception: It demonstrated a 38% reduction in HIV incidence with syndromic STI management (Grosskurth, 1995). Nonetheless, the strong link between the two argues for the importance of regular screening and treatment for STIs in those at risk because those who screen positive are likely to benefit from PrEP and risk reduction counseling in general. This point is highlighted by an analysis from New York City that demonstrated that 1 in 20 MSM with a new syphilis diagnosis were diagnosed with HIV within 1 year (Prathela, 2015).

Voluntary Medical Male Circumcision

Three large randomized trials performed in sub-Saharan Africa demonstrated that voluntary circumcision of HIV-uninfected men led to an approximate risk reduction for heterosexual HIV acquisition of 50% (Auvert, 2005; Bailey, 2007; Gray, 2007; Siegfried, 2009). This prevention benefit does not appear to extend to the female partners of circumcised HIV-infected men (Weiss, 2009). Although observational data suggest that circumcision may be beneficial for MSM who practice primary insertive anal intercourse, there is currently insufficient evidence to determine whether or not this is the case in general for MSM (Wiysonge, 2011).

Vertical Transmission Prevention

This is reviewed in detail in Chapter 26.

Treatment as Prevention

This is reviewed in detail in Chapter 23.

Recommended Reading

New York State Department of Health AIDS Institute. HIV prophylaxis following non-occupational exposure. Available at http://www.hivguidelines.org/clinical-guidelines/post-exposure-prophylaxis/hiv-prophylaxis-following-non-occupational-exposure.

Siegfried N, Muller M, Deeks JJ, et al. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2009;2:CD003362. DOI: 10.1002/14651858.CD003362.pub2Find this resource:

US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States–2014: A clinical practice guideline. Available at http://stacks.cdc.gov/view/cdc/23109.

Investigational Interventions

Intermittent and On-demand Pre-exposure Prophylaxis

As previously mentioned, currently approved PrEP regimens require the daily use of antiretrovirals. Alternative dosing schedules, including on-demand and time-driven use of oral formulations as well as the use of long-acting injectable formulations, are under active investigation. Also as mentioned previously, mixed results have been obtained from studies evaluating non-daily oral PrEP use. The IPERGAY study conducted in France, Quebec, Canada, and other French-speaking countries evaluated event-driven PrEP in high-risk MSM. Participants in the intervention arm of this prospective, randomized, placebo-controlled trial took two tablets of TDF/FTC 2–24 hours before sex, 1 tablet 24 hours after sex, and an additional tablet 48 hours after the first dose. This on-demand approach was highly effective, with an 86% reduction in the risk of HIV seroconversion among those in the intervention arm compared to placebo (Molina, 2015). On the other hand, in the HPTN 067/ADAPT Harlem study, which compared daily PrEP with time-driven (one dose twice weekly plus one dose after sex) and event-driven (one dose before and one dose after sex) dosing schedules among MSM and transgender women in the United States, the daily strategy provided better coverage of reported sex acts and higher overall adherence compared to the other two (Mannheimer, 2015). It is also important to note that there are concerns about the use of nondaily strategies in different populations based on varying levels of drug penetration into different tissue categories. For example, oral tenofovir appears to concentrate more quickly in rectal compared to vaginal mucosa (Hendrix, 2013), which could limit the applicability of event- and time-driven PrEP in women.

Another investigational strategy is the use of long-acting injectable antiretrovirals for PrEP. Both cabotegravir, a novel integrase strand transfer inhibitor, and the non-nucleoside reverse transcriptase inhibitor rilpivirine can be formulated for depot injection and could potentially be given every 3 months as single agents, or in combination, for prevention (Ford, 2013; Snyder, 2014; Spreen, 2014). Concerns about dosing due to pharmacokinetic variability and the potential to select for HIV drug resistance as patients discontinue these drugs remain (Jackson, 2015; Penrose, 2015). Phase II trials (HPTN 076, HPTN 077, and HPTN 083) are currently underway or will soon be enrolling to further investigate the pharmacokinetics, safety, and tolerability of these agents (Krakower, 2015; see www.hptn.org).

Microbicides

Microbicides are products that are applied locally to the vaginal or rectal mucosa to reduce the risk of HIV, and other STI, acquisition. There was great optimism for this strategy when the results of the CAPRISA 004 trial were released. This study examined the effectiveness and safety of coitally dosed (one dose within 12 hours before sex and a second dose as soon as possible within 12 hours after sex) 1% tenofovir vaginal gel in sexually active South African women aged 18–40 years. It was found that use of this gel resulted in a 39% reduction overall in the risk of HIV acquisition and a 54% reduction in those who used the gel at least 80% of the time (Abdool Karim, 2010). However, this optimism was dampened by the failure of two subsequent studies, VOICE and FACTS 001, to show any reduction in HIV acquisition among women using this same tenofovir gel (Marrazzo, 2015; Rees, 2015). Note that HIV acquisition was reduced by approximately 50% among women who used the gel consistently, as measured by plasma TDF levels in both studies (Dai, 2015; Rees, 2015).

Despite the previously mentioned disappointment, the use of microbicides or other local drug-delivery devices such as vaginal rings has several theoretical benefits. First, they deliver high concentrations of the drug to the desired tissue with minimal systemic exposure (Hendrix, 2013). As such, they have the potential to provide on-demand protection, especially considering the time delay that occurs between oral TDF dosing and drug penetration of the vaginal mucosa. These products also may be given to women, who comprised almost half of new HIV infections globally in 2014 (WHO, 2015), and represent an additional HIV preventive option that they can control. Last, they have the potential to be co-formulated with other medications and as such may provide protection against other STIs and pregnancy. Ongoing studies currently evaluating novel microbicide approaches include several examining drug-eluting vaginal rings that can be left in the vagina for up to 1 month at a time and that contain TDF, darunavir, maraviroc, or dapivirine, with or without a hormonal contraceptive, usually levonorgestrel; and another study evaluating the use of a rectal gel for MSM and women who engage in receptive anal intercourse (Krakower, 2015). Importantly, results of the MTN-020/ASPIRE trial, which evaluated the efficacy of a monthly dapivirine-eluting vaginal ring for HIV prevention in at-risk African women, were recently released and demonstrated a modest 27% reduction in the incidence of new HIV infections among women who received the study ring compared to those who received placebo. Adherence was again an important factor because the efficacy of the ring increased to 37% when data from two study sites with reduced rates of adherence and retention were excluded (Baeten, 2016). Although the overall protective effect was not as great as seen with other PrEP methods, this study offers hope for women-controlled prevention options.

Vaccines

Multiple challenges, both biomedical and social, have impeded the development of an effective HIV vaccine. These include HIV viral diversity and pathogenesis, identification of appropriate immune correlates of protection, community preparedness and concerns about vaccine-induced positivity, and, more recently, the expanded use of PrEP (Hammer, 2015). With the exception of the modestly positive Thai vaccine trial, which demonstrated a 31% reduction in new infections among vaccine recipients, clinical trials of HIV preventive vaccines have had disappointing results (Table 4.7). However, the pursuit of an effective vaccine remains as important as ever. Even with the promise of ART-mediated control of the epidemic through TasP and PrEP, an effective vaccine is essential for timely, sustainable control to occur, given the complexities of human behavior and the risk that programs supporting treatment-based interventions could be defunded over time (Fauci, 2014). The ability of a vaccine to elicit broadly neutralizing antibodies (BNAbs), or antibodies that can protect against multiple pathogenic HIV strains by binding to highly conserved regions of the virus, is crucial for its success but thus far has been elusive. Recent advances in the identification and understanding of BNAbs have injected new hope into HIV vaccine development. One such antibody product, VRC01, is currently under investigation in the AMP study, a collaborative HVTN/HPTN study expected to begin enrollment in late 2015/early 2016 (see http://ampstudy.org). The use of bioinformatically developed mosaic antigens to elicit antibody responses that are protective against all clades of HIV is another novel approach that is under investigation in the HIV-V-A004 trial (Barouch, 2013; see http://www.avac.org/trial/hiv-v-a004ipcavd-009-approach).

Table 4.7 Summary of HIV Vaccine Efficacy Trials

Trial

Vaccine Product

Study Population; Site

Results

Reference

Vax 003

Recombinant gp120 (B/E)

Male and female PWID; Thailand

No efficacy

Pitisuttithum (2006)

Vax 004

Recombinant gp120 (B/B′)

Heterosexual women and MSM; United States and the Netherlands

No efficacy

Flynn (2005)

HVTN 502

Recombinant Ad5 (Clade B gag/pol/nef)

MSM, heterosexual women and men; North and South America, Caribbean, Australia

No efficacy

Buchbinder (2008)

HVTN 503

Recombinant Ad5 (Clade B gag/pol/nef)

Heterosexual women and men; South Africa

No efficacy

Gray (2011)

HVTN 505

  • 6-plasmid DNA vaccine and rAd5

  • vector boost

MSM; United States

No efficacy

Hammer (2013)

RV 144

ALVAC: Canarypox (gag, pol, env) + AIDSVAX B/E recombinant gp120

Heterosexual women and men; Thailand

31% reduction in acquisition

Rerks-Ngarm (2009)

MSM, men who have sex with men; PWID, people who inject drugs.

source: Adapted from Tieu (2013) and Rubens (2015).

Recommended Reading

Fauci AS, Marston HD. Ending AIDS—Is an HIV vaccine necessary? N Engl J Med. 2014;370(6):495–498.Find this resource:

Krakower DS, Mayer KH. Pre-exposure prophylaxis to prevent HIV infection: Current status, future opportunities and challenges. Drugs. 2015;75:243–251.Find this resource:

Conclusion

Tremendous progress has been made in the field of HIV transmission prevention. Although recent attention has focused on ART-based interventions such as TasP and PrEP, a truly multifaceted approach that includes behavioral, structural, and novel biomedical interventions will be needed to have a significant, lasting impact on the global incidence of HIV.

Questions and Answers

This chapter in Fundamentals of HIV Medicine has accompanying questions that can be answered for continuing medical education (CME) credit. To access these questions, visit www.cmeuniversity.com and enter course ID 11635 in the “Find Post-test/Evaluation by Course” field. Access to CME credit expires April 2018.

References

Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329(5996): 1168–1174.Find this resource:

Abdul-Quader AS, Feelemyer J, Modi S, et al. Effectiveness of structural-level needle/syringe programs to reduce HCV and HIV infection among people who inject drugs: a systematic review. AIDS Behav 2013; 17(9): 2878–2892.Find this resource:

Adimora AA, Hughes JP, Wang J, et al. Characteristics of multiple and concurrent partnerships among women at high risk for HIV infection. J Acquir Immune Defic Syndr 2014; 65(1): 99–106.Find this resource:

Adler NE. Overview of health disparities. In: GE Thompson, F Mitchell, M Williams, eds. Examining the health disparities research plan of the National Institutes of Health: Unfinished business. Washington, DC: National Academic Press, 2006; 129–188.Find this resource:

Agerwala SM, McCance-Katz EF. Integrating Screening, Brief Intervention, and Referral to Treatment (SBIRT) into clinical practice settings: A brief review. J Psychoactive Drugs 2012; 44(4): 307–317.Find this resource:

Aidala AA, Wilson MG, Shubert V, et al. Housing status, medical care, and health outcomes among people living with HIV/AIDS: A systematic review. Am J Public Health 2015; 106: e1–e23.Find this resource:

Althoff KN, Gebo KA, Gange SJ, et al. CD4 count at presentation for HIV care in the United States and Canada: Are those over 50 years more likely to have a delayed presentation? AIDS Res Ther 2010; 7: 45.Find this resource:

Anderson BJ. HIV stigma and discrimination persist, even in health care. AMA J Ethics 2009; 11(12): 998–1001.Find this resource:

Anema A, Marshall BD, Stevenson B, et al. Intergenerational sex as a risk factor for HIV among young men who have sex with men: A scoping review. Curr HIV/AIDS Rep 2013; 10(4): 398–407.Find this resource:

Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989–31 January 2015. Available at http://www.apregistry.com/forms/exec-summary.pdf. Accessed November 29, 2015.

Aspinall EJ, Nambiar D, Goldberg DJ, et al. Are needle and syringe programs associated with a reduction in HIV transmission among people who inject drugs: A systematic review and meta-analysis? Int J. Epidemiol 2014; 43(1): 235–248.Find this resource:

Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial. PLoS Med 2005; 2(11): e298.Find this resource:

Baeten JM. Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367: 399–410.Find this resource:

Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med. 2016 Feb 22. [Epub ahead of print]Find this resource:

Baggaley R, Boily M-C, White RG, et al. Risk of HIV-1 transmission for parenteral exposure and blood transfusion: a systematic review and meta-analysis. AIDS 2006; 20(6): 805–812.Find this resource:

Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369: 643Find this resource:

Barouch DH, Stephenson KE, Borducchi EN et al. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell 2013; 155(3):531–539.Find this resource:

Bonell C, Imrie J. Behavioral interventions to prevent HIV infection: rapid evolution, increasing rigor, moderate success. Br Med Bull 2001; 58(1): 155–170.Find this resource:

Branson BM, Handsfield HH, Lampe MA, et al.; Centers for Disease Control and Prevention. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep 2006; 55(RR-14): 1–17.Find this resource:

Brooks JT, Buchacz K, Gebo K, et al. HIV infection and older Americans: The public health perspective. Am J Public Health 2012; 102(8): 1516–1526.Find this resource:

Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine(the Step Study): A double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 2008; 372(9653): 1881–1893.Find this resource:

Burris S, Chiu J. Punitive Drug Law and the Risk Environment for Injecting Drug Users: Understanding the Connections. Working paper prepared for the Third Meeting of the Technical Advisory Group of the Global Commission on HIV and the Law, 7–9 July 2011. Available at http://hivlawcommission.org/index.php/working-papers?view=document&id=98&tmpl=component. Accessed November 17, 2015.

Busch MP, Kleinman SF, Nemo GJ. Current and emerging infectious risks of blood transfusions. JAMA 2003; 289(8): 959–962.Find this resource:

Bush S, Ng L, Magnuson D, et al. Significant Uptake of Truvada for Pre-exposure Prophylaxis (PrEP) Utilization in the US in Late 2014–1Q2015. In: Abstracts of the 10th International Conference on HIV Treatment and Prevention Adherence, Miami, FL, 2015. Abstract 74. Available at http//iapac.org/AdherenceConference/presentations/ADH10_OA74.pdf. Accessed November 29, 2015.Find this resource:

Caceres CF, Gerbase A, Lo YR, et al. Prevention and Treatment of HIV and Other Sexually Transmitted Infections Among Men Who Have Sex with Men and Transgender People: Recommendations for a Public Health Approach. Geneva: World Health Organization Document Production Services, 2011.Find this resource:

Cardo DM, Culver DH, Ciesielski CA, et al.; Centers for Disease Control and Prevention Needlestick Surveillance Group. A case control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med 1997; 337(21):1485–1490.Find this resource:

Celentano DD, Lucas G. Optimizing treatment outcomes in HIV-infected patients with substance abuse issues. Clin Infect Dis 2007; 45 (Suppl. 4): S318–S323.Find this resource:

Centers for Disease Control and Prevention. HIV transmission through transfusion—Missouri and Colorado, 2008. MMWR Morb Mortal Wkly Rep 2010; 59: 1335–1339.Find this resource:

Centers for Disease Control and Prevention. Integrated prevention services for HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use drugs illicitly: Summary guidance from CDC and the U.S. Department of Health and Human Services. MMWR 2012; 61(RR-5): 1–46.Find this resource:

Centers for Disease Control and Prevention, Health Resources and Services Administration, National Institutes of Health, American Academy of HIV Medicine, Association of Nurses in AIDS Care, International Association of Providers of AIDS Care, the National Minority AIDS Council, and Urban Coalition for HIV/AIDS Prevention Services. Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. December 11, 2014. Available at http://stacks.cdc.gov/view/cdc/26062.

Centers for Disease Control and Prevention. HIV and Injection Drug Use in the United States. Available at http://www.cdc.gov/hiv/risk/idu.html. Accessed November 11, 2015.

Chen M, Rhodes PH, Hall HI, et al. Prevalence of undiagnosed HIV infection among persons aged ≥13 years—National HIV Surveillance System, United States, 2005–2008. MMWR Suppl. 2012; 61(02): 57–64.Find this resource:

Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2013; 381: 2083–2090.Find this resource:

Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral treatment prevents HIV transmission: final results from the HPTN 052 randomized controlled trial. Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention; July 19-22, 2015; Vancouver, Canada. Abstract MOAC0101LB.Find this resource:

Dai JY, Hedrix CW, Richardson BA, et al. Pharmacological measures of treatment adherence and risk of HIV infection in the VOICE study. J Infect Dis. DOI: 10.1093/infdis/jiv333. [Epub ahead of print]Find this resource:

Degenhardt L, Mathers B, Guarinieri M, et al. Meth/amphetamine use and associated HIV: Implications for global policy and public health. Int J Drug Policy 2010; 21(5): 347–358.Find this resource:

Dominguez K, Smith DK, Vasavi T, et al. Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016. U.S. Centers for Disease Control and Prevention. Available at http://stacks.cdc.gov/view/cdc/38856. Accessed April 25, 2016.

Fauci AS, Martson HD. Ending AIDS—Is an HIV vaccine necessary? N Engl J Med 104; 370(6):495–498.Find this resource:

Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 2005; 191(5):654–665.Find this resource:

Ford SL, Gould E, Chen S, et al. Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Antimicrob Agents Chemother 2013; 57(11):5472–5477.Find this resource:

Garcia J, Parker C, Parker RG, et al. “You’re really gonna kick us all out?” Sustaining safe spaces for community-based HIV prevention and control among black men who have sex with men. PLoS One 2015; 10(10): e0141326.Find this resource:

Garfein RS, Golub ET, Greenberg AE, et al. A peer-education intervention to reduce injection risk behaviors for HIV and hepatitis C virus infection in young injection drug users. AIDS 2007; 21: 1923–1932.Find this resource:

Giannou FK, Tsiara CG, Nikolopoulos GK, et al. Condom effectiveness in reducing heterosexual HIV transmission: A systematic review and meta-analysis of studies on HIV serodiscordant couples. Expert Rev Pharmacoecon Outcomes Res 2015; 1–11.Find this resource:

Grant RM., Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587–2599.Find this resource:

Gray GE, Allen M, Moodie Z, et al. Safety and efficacy assessment of the HVTN 503/Phambili Study: A double-blind randomized placebo-controlled test-of-concept study of a Clade B-based HIV-1 vaccine in South Africa. Lancet Infect Dis 2011; 11(7): 507–515.Find this resource:

Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. Lancet 2007; 369: 657–666.Find this resource:

Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: Randomised controlled trial. Lancet 1995; 346: 530–536.Find this resource:

Hammer SM. Advances in preventive HIV vaccines: Efficacy trial evolution. ID Week 2015; October 7-11, 2015; San Diego, California. Oral session 0021.Find this resource:

Hammer SM, Sobieszczyk ME, Janes H, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 2013; 369: 2083–2092.Find this resource:

Harrison A, Cleland J, Frohlick J. Young people’s sexual partnerships in KwaZulu/Natal, South Africa: Patterns, contextual influences, and HIV risk. Studies Fam Planning 2008; 39(4): 295–308.Find this resource:

Heimer R, Abdala N. Viability of HIV-1 in syringes: Implications for interventions among injection drug users. AIDS Reader 2000; 10(7).Find this resource:

Heimer R, Grau LE, Curtin E, et al. Assessment of HIV testing of urban injection drug users: Implications for expansion of HIV testing and prevention efforts. Am J Public Health 2007; 97(1): 119–116.Find this resource:

Hendrix CW, Chen BA, Guddera V, et al. MTN-001: Randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLoS One 2013; 8(1): e55013. doi:10.1371/journal.pone.0055013.Find this resource:

Hosein SR and Wilson DP. Decision-making by people living with HIV requires communications from clinicians about the risk of transmission despite undetectable plasma viral load. HIV Med 2011; 12(8):516.Find this resource:

HRSA CARE Action [newsletter]. Methamphetamines and HIV. June 2009. Available at http://hab.hrsa.gov/newspublications/careactionnewsletter/june2009.pdf. Accessed November 15, 2015.

HRSA CARE Action [newsletter]. Impact of mental illness on people living with HIV. January 2015. Available at http://hab.hrsa.gov/deliverhivaidscare/mentalhealth.pdf. Accessed November 24, 2015.

Hosek S, Rudy B, Landowitz R, et al. An HIV pre-exposure prophylaxis (PrEP) demonstration project and safety study for young men who have sex with men in the United States (ATN 110). Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention; July 19-22, 2015; Vancouver, Canada. Abstract TUAC0204LB.Find this resource:

Humeniuk, R, Dennington V, Ali R; WHO ASSIST Phase III Study Group. The effectiveness of brief intervention for illicit drugs linked to the alcohol, smoking and substance involvement screening test (ASSIST) in primary health care settings: a technical report of phase III findings of the WHO ASSIST randomized controlled trial. Geneva: World Health Organization Document Production Services, 2008.Find this resource:

Institute of Medicine. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: an Assessment of the Evidence. Washington, DC: National Academies Press, 2007.Find this resource:

Jackson A, McGowan I. Long-acting rilpivirine for HIV prevention. Curr Opin HIV AIDS 2015; 10(4):253–257.Find this resource:

Kaufman M, Cornish F, Zimmerman RS, et al. Health behavior change models for HIV prevention and AIDS care: Practical recommendations for a multi-level approach. J Acquir Immune Defic Syndr. 2014; 66 (Suppl 3): S250–S258.Find this resource:

Kaushic C, Ferreira VH, Kafka JK, et al. HIV infection in the female genital tract: Discrete influence of the local mucosal microenvironment. Am J Reprod Immunol 2010; 63(6): 566–575.Find this resource:

Kennedy CE, Medley AM, Sweat MD, et al. Behavioral interventions for HIV positive prevention in developing countries: A systematic review and meta-analysis. Bull World Health Organization 2010; 88: 615–623.Find this resource:

Kerr T, Kimber J, Debeck K, et al. The role of safer injection facilities in the response to HIV/AIDS among injection drug users. Curr HIV/AIDS Rep 2007; 4(4): 158–164.Find this resource:

Kleinman SH, Lelie N, Busch MP. Infectivity of human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus and risk of transmission by transfusion. Transfusion 2009; 49(11): 2454–2489.Find this resource:

Krakower DS, Mayer KH. Pre-exposure prophylaxis to prevent HIV infection: Current status, future opportunities and challenges. Drugs 2015; 75:243–251.Find this resource:

Kuhar DT, Henderson DK, Struble KA et al. Updated USPHS guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for post-exposure prophylaxis. Infect Control Hosp Epidemiol. 2013 Sept; 34(9):875–892.Find this resource:

Latkin CA, Davey-Rothwell MA, Knowlton AR, et al. Social network approaches to recruitment, HIV prevention, medical care, and medication adherence. J Acquir Immune Defic Syndr 2013; 63 (Suppl 1): S54–S58.Find this resource:

Latkin C, Donnell D, Metzger D, et al. The efficacy of a network intervention to reduce HIV risk behaviors among drug users and risk partners in Chiang Mai, Thailand and Philadelphia, US. Soc Sci Med 2009; 68(4): 740–748.Find this resource:

LawAtlas: The Policy Surveillance Portal. Report—Syringe Distribution Laws (April 2015). Available at http://lawatlas.org/files/upload/20150421_SyringeD_Report.pdf. Accessed November 17, 2015.

Lehman DA, Baeten JM, McCoy CO, et al. Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent prophylaxis. J Infect Dis 2015; 211:1211–1218.Find this resource:

Lourenco L, Colley G, Nosyk B, et al.; STOP HIV/AIDS Study Group. High levels of heterogeneity in the HIV cascade of care across different population subgroups in British Columbia, Canada. PLoS One 2014; 9(12): e115277.Find this resource:

Lunding S, Katzenstein TL, Kronborg G, et al. The Danish PEP Registry: Experience with the use of post-exposure prophylaxis following blood exposure to HIV from 1999-2012. Infect Dis (Lond). 2015 Nov 3:1-6. [Epub ahead of print].Find this resource:

MacArthur GJ, Minozzi S, Martin N, et al. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ 2012; 345: e5945.Find this resource:

MacArthur GJ, van Velzen E, Palmateer N, et al. Interventions to prevent HIV and hepatitis C in people who inject drugs: A review of reviews to assess evidence of effectiveness. Int J Drug Policy 2014; 25(1): 34–52.Find this resource:

Mahajan AP, Sayles JN, Patel VA, et al. Stigma in the HIV/AIDS epidemic: A review of the literature and recommendations for the way forward. AIDS 2008; 22 (Suppl 2): S67-S79.Find this resource:

Mannheimer S, Hirsch-Moverman Y, Loquere A, et al. HPTN 067ADPAT study: A comparison of daily and intermittent Pre-exposure prophylaxis (PrEP) for HIV prevention in men who have sex with men and transgender women in New York City. 8th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. 2015; Vancouver, Canada. Abstract MOAAC0305LB.Find this resource:

Marks G, Crepaz N, Senterfitt JW, et al. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: Implications for HIV prevention programs. J Acquir Immune Defic Syndr 2005; 39(4): 446–453.Find this resource:

Marrazzo JM, del Rio C, Holtgrave DR, et al. HIV prevention in clinical care settings: 2014 recommendations of the International Antiviral Society—USA Panel. JAMA 2014; 312(4):390–409.Find this resource:

Marrazzo JM, Gita R, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med 2015; 372: 509–518.Find this resource:

Mayer KH, Venkatesh KK. Interactions of HIV and other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquisition. Am J Reprod Immunol 2011; 65: 308–316.Find this resource:

McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2015 Sep 9. pii: S0140-6736(15)00056-2. doi: 10.1016/S0140-6736(15)00056-2.Find this resource:

Medley A, Kennedy C, O’Reilly K, et al. Effectiveness of peer education interventions for HIV prevention in developing countries: A systematic review and meta-analysis. AIDS Educ Prev 2009; 21(3): 181–206.Find this resource:

Metzger DS, Zhang Y. Drug treatment as HIV prevention: Expanding treatment options. Curr HIV/AIDS Rep 2010; 7(4): 220–225.Find this resource:

Molina JM, Capitant C, Charreau I, et al. On demand PrEP with oral TDF/FTC in MSM: Results of the ANRS Ipergay trial. N Engl J Med 2015; 373:2237–2246.Find this resource:

Mulligan K, Glidden DV, Anderson PL, et al. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2015; 61(4):572–580.Find this resource:

Needle RH, Burrows D, Friedman SR, et al. Effectiveness of community-based outreach in preventing HIV/AIDS among injecting drug users. Int J Drug Pol 2005; 16 (Suppl): S45–S57.Find this resource:

New York State Department of Health AIDS Institute. Guidance for the use of pre-exposure prophylaxis (PrEP) to prevent HIV transmission, Oct 2015 revision. Available at http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission. Accessed November 25, 2015.

New York State Department of Health AIDS Institute. HIV prophylaxis following non-occupational exposure. Available at http://www.hivguidelines.org/clinical-guidelines/post-exposure-prophylaxis/hiv-prophylaxis-following-non-occupational-exposure. Accessed October 26, 2015.

New York State Department of Health AIDS Institute. HIV prophylaxis for victims of sexual assault. Available at http://www.hivguidelines.org/clinical-guidelines/post-exposure-prophylaxis/hiv-prophylaxis-for-victims-of-sexual-assault.

Nosyk B, Min JE, Evans E, et al. The effects of opioid substitution treatment and highly active antiretroviral therapy on the cause-specific risk of mortality among HIV-positive people who inject drugs. Clin Infect Dis 2015; 61(7): 1157–1165.Find this resource:

Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol 2000; 74(20):9771–9775.Find this resource:

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed April 15, 2015.

Penrose K, Parikh UM, Hamanishi KA, et al. Selection of rilpivirine resistant HIV-1 in a seroconverter on long-acting rilpivirine (TMC278LA) from the lowest dose arm of the SSAT040 trial. J Infect Dis 2015; [Epub ahead of print]Find this resource:

Pettifor A, Bekker L-G, Hosek S, et al. Preventing HIV among young people: Research priorities for the future. J Acquir Immune Defic Syndr 2013; 63 (Suppl 2): S155-S160.Find this resource:

Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 2006; 194:1671–71.Find this resource:

Prathela P, Brauntein SL, Blank S, et al. The high risk of an HIV diagnosis following a diagnosis of syphilis: a population-level analysis of New York City men. Clin Infect Dis 2015; 61(2):281–287.Find this resource:

Rees H, Delany-Moretlwe SA, Lombard C, et al. FACTS 001 phase III trial of pericoital tenofovir 1% gel for HIV prevention in women. Program and abstracts of the 2015 Conference on Retroviruses and Opportunistic Infections; February 2015; Seattle, Washington. Abstract 26LB.Find this resource:

Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361:2209–2220.Find this resource:

Rothman F, Rudnick D, Slifer M, et al. Co-located substance use treatment and HIV prevention and primary care services, New York State, 1990–2002: A model for effective service delivery to a high-risk population. J Urban Health 2007; 84(2): 226–242.Find this resource:

Rubens M, Ramamoorthy V, Saxena A, et al. HIV vaccine: Recent advances, current roadblocks, and future directions. J Immunol Res 2015; 2015: Epub 2015 Oct 22.Find this resource:

Saitz R. Screening and brief intervention for unhealthy drug use: Little or no efficacy. Fron Psychiatry 2014; 5: 121.Find this resource:

Shih CC, Kaneshima H, Rabin L, et al. Post exposure prophylaxis with zidovudine suppresses human immunodeficiency virus type 1 infection in SCID-hu mice in a time-dependent manner. J Infect Dis 1991; 163(3):625–627.Find this resource:

Shubert G; for the National Minority AIDS Council and Housing Works. Mass Incarceration, Housing Instability, and HIV/AIDS: Research Findings and Policy Recommendations. February 2013.Find this resource:

Siegfried N, Muller M, Deeks JJ, et al. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev 2009;2:CD003362. DOI: 10.1002/14651858.CD003362.pub2Find this resource:

Sikkema KJ, Watt MH, Drabkin AS, et al. Mental health treatment to reduce HIV transmission risk behavior: A positive prevention model. AIDS Behav 2010; 14(2): 252–262.Find this resource:

Smith DK, Herbst JH, Zhang XJ, et al. Condom effectiveness for HIV prevention by consistency of use among men who have sex with men (MSM) in the US. J Acquir Immune Defic Syndr 2015; 68(3): 337–344.Find this resource:

Snyder O, Vincent H, Lachau-Durant S, et al. Preclinical evaluation of TMC-278 LA, a long-acting formulation of rilpivirine, demonstrates significant protection from vaginal HIV infection. AIDS Res Hum Retroviruses 2014; 30 (Suppl 1): A11–A12.Find this resource:

Solomon MM, Lama JR, Glidden DV, et al. Changed in renal function associated with oral FTC/TDF use for HIV pre-exposure prophylaxis. AIDS 2014;28:851–859Find this resource:

Solomon MM, Schechter M, Liu AY, et al. The safety of tenofovir-emtricitabine for HIV pre-exposure prophylaxis (PrEP) in individuals with active hepatitis B. J Acquir Immune Defic Syndr 2015 Sep 21. [Epub ahead of print].Find this resource:

Spiller MW, Broz D, Wejnert C, et al.; Centers for Disease Control and Prevention; National HIV Behavioral Surveillance System Study Group. HIV infection and HIV-associated behaviors among persons who inject drugs—20 cities, United States, 2012. MMWR Morb Mortal Wkly Rep 2015; 64(10): 270–275.Find this resource:

Spreen B, Rinehart A, Smith K, et al. HIV PrEP dose rationale for cabotegravir (GSK 1265744) long-acting injectable nanosuspension. AIDS Res Hum Retroviruses 2014; 30(Suppl 1):A12.Find this resource:

Strathdee SA, Beyrer C. Threading the needle—How to stop the HIV outbreak in rural Indiana. N Engl J Med 2015; 373: 397–399.Find this resource:

Strathdee SA, Shoptaw S, Dyer TP, et al.; Substance Use Scientific Committee of the HIV Prevention Trials Network. Towards combination HIV prevention for injection drug users: Addressing addictophobia, apathy and inattention. Curr Opin HIV AIDS 2012; 7(4): 320–325.Find this resource:

Substance Abuse and Mental Health Services Administration. White Paper on Screening, Brief Intervention and Referral to Treatment (SBIRT) in Behavioral Healthcare- 2011. Rockville, MD, 2011.Find this resource:

Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367:423–434.Find this resource:

Tieu HV, Rolland M, Hammer SM, et al. Translational research insights from completed HIV vaccine efficacy trials. J Acquir Immune Defic Syndr 2013; 63:S150–S154.Find this resource:

US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States—2014: A clinical practice guideline. http://stacks.cdc.gov/view/cdc/23109.

Valdiserri RO. HIV/AIDS stigma: An impediment to public health. Am J Public Health 2002; 92(3): 341–342.Find this resource:

Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012; 367: 411–422.Find this resource:

Vlahov D, Robertson AM, Strathdee SA. Prevention of HIV infection among injection drug users in resource-limited settings. Clin Infect Dis 2010; 50(Suppl 3): S114–S121.Find this resource:

Volk JE, Marcus JL, Phengrasamy T, et al. No new HIV infections with increasing use of HIV preexposure prophylaxis in a clinical practice setting. Clin Infect Dis 2015; 61(10):1601–1603.Find this resource:

Wagner Z, Wu Y, Sood N. The Affordable Care Act my increase the number of people getting tested for HIV by nearly 500,000 by 2017. Health Aff (Millwood) 2014; 33(3): 378–385.Find this resource:

Ward H, Rönn M. The contribution of STIs to the sexual transmission of HIV. Curr Opin HIV AIDS 2010; 5(4): 305–310.Find this resource:

Wei C, Fisher Raymond H, Guadamuz TE, et al. Racial/ethnic differences in seroadaptive and serodisclosure behaviors among men who have sex with men. AIDS Behav 2011; 15(1): 22–29.Find this resource:

Weiss HA, Hankins CA, Dickson K. Male circumcision and risk of HIV infection in women: A systematic review and meta-analysis. Lancet Infect Dis 2009; 9: 669–677.Find this resource:

Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev 2002; 1: CD003255.Find this resource:

Wiysonge CS, Kongnyuy EJ, Shey M, et al. Male circumcision for prevention of homosexual acquisition of HIV in men. Cochrane Database Syst Rev 2011;6.CD007496. DOI:10.1002/14651858.CD007496.pub2Find this resource:

Wodak A, Cooney, A. Effectiveness of Sterile Needle and Syringe Programming in Reducing HIV/AIDS Among Injecting Drug Users. Geneva: World Health Organization Document Production Services, 2004.Find this resource:

Woodring J, Kruszon-Moran D, McQuillan G. HIV infection in U.S. household population aged 18–59: Data from the National Health and Nutrition Examination Survey, 2007–2012. Natl Health Stat Report 2015 Sep 24;(83):1–13Find this resource:

World Health Organization. Global Summary of the AIDS Epidemic, 2014. Available at http://www.who.int/hiv/data/en. Accessed November 29, 2015.

World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, 2015. Available at http://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en. Accessed November 8, 2015.

Young TN, Arens FJ, Kennedy GE, et al. Antiretroviral post-exposure prophylaxis (PEP) for occupational HIV exposure. Cochrane Database Sys Rev. 2007;1:CD002835.Find this resource:

Zanakis SH, Alvarez C, Li V. Socio-economic determinants of HIV/AIDS pandemic and nations efficiencies. Eur J Operational Res 2007; 176: 1811–1838.Find this resource:

Zou S, Dorsey KA, Notari EP, et al. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 2010; 50(7): 1495–1504.Find this resource: