HIV pre-exposure prophylaxis for people who inject drugs

HIV prevention in people who inject drugs

According to the CDC, 9% of incident HIV cases in the United States are directly attributable to injection drug use [ ]. Among people who inject drugs (PWID), the risk for HIV and other blood-borne pathogens is primarily related to injecting behaviors, including sharing needles, syringes, and other injecting and drug preparation equipment. Data from the National HIV Behavioral Surveillance System reflects that approximately 34% of PWID share syringes and 58% share other injection paraphernalia [ ]. In the setting of ongoing and untreated substance use, PWID also experience heightened risk for HIV related to sex because of (1) sex in the context of intoxication with associated disinhibition, (2) high-risk sex networks, and/or (3) sexual bartering (i.e., exchanging sex for drugs, money, goods, or other services). Women who inject drugs experience “double risk” for HIV because of overlapping sex and drug use networks [ ]. HIV risk among PWID is compounded by concomitant infections with hepatitis B and C that are more prevalent in PWID (a topic addressed more completely in Chapter 6 and 2).

PWID not only experience inordinate risk for HIV but also face numerous barriers to engaging with effective prevention and treatment services for HIV. Despite the high HIV risk, PWID often have less access to prevention innovations because of stigmatization, underinsurance, poor socioeconomic status, homelessness, criminal justice involvement, and other challenges navigating systems of care and support. In the setting of the current opioid epidemic, in which there are increasing numbers of PWID, particularly in nonurban settings, access to harm reduction and HIV prevention resources is often limited. As multiple recent hepatitis C virus and HIV outbreaks in the United States illustrate, PWID experience a high burden of HIV risk, particularly when resources are not available or accessible to reduce harms associated with injecting [ , ].

PWID are a key target population for HIV prevention in the global and US national strategies [ , ]. A number of evidence-based HIV prevention approaches are available for PWID, including treatment for opioid use disorder with medication-assisted therapy (MAT), syringe services programs (SSPs) for harm reduction, frequent testing for HIV and sexually transmitted infections, and barrier protection (i.e., condoms) to reduce HIV risk associated with sex. Outcomes are optimized when these approaches are used together, known as “combination prevention” ( Fig. 11.1 ).

In light of the US opioid crisis, multiple methods of HIV prevention are needed for PWID. HIV preexposure prophylaxis (PrEP) is an important addition to the HIV prevention armamentarium for PWID. PrEP is grounded in the principle that giving antiretrovirals to people without HIV (but who are at high risk for acquiring HIV) is effective in preventing infection in spite of exposure, as is the case of prevention of maternal to child transmission of HIV. At present, the only FDA-approved medications for PrEP are tenofovir diphosphate (tenofovir disoproxil fumarate [TDF]) or tenofovir alafenamide fumarate (TAF) given in combination with emtricitabine (FTC). Co-formulated TDF/FTC (manufactured by Gilead and sold as Truvada) or TAF/FTC (manufactured by Gilead and sold as Descovy) are available as single-tablet daily medication. Other dosing strategies (e.g., “on-demand” pericoital dosing) and formulations (e.g., TDF 1% vaginal gel) are investigational in select populations or not yet widely used in the United States. In a meta-analysis, TDF alone was shown to be equally effective as TDF/FTC. Other medications for PrEP, including injectable cabotegravir and a dapivirine vaginal ring are currently in development and testing. In multiple large randomized clinical trials of men who have sex with men (MSM) and serodiscordant heterosexual couples, PrEP was significantly effective at preventing HIV when it was taken consistently [ ]. In this chapter, we review the evidence and indications for PrEP in PWID and discuss strategies to address key challenges to scale-up.

Evidence of efficacy of preexposure prophylaxis in people who inject drugs

To date, there has been a single large randomized clinical trial for PrEP in PWID, known as the Bangkok Tenofovir Study (BTS) [ ]. The BTS was a phase III randomized, double-blind, placebo-controlled trial conducted in Thailand. The study population was recruited from 17 Bangkok Metropolitan Administration drug treatment clinics and composed of 1924 men and 489 women who had injected drugs in the past year, excluding pregnant women, people with chronic hepatitis B, and people already diagnosed with HIV-1. About 22% of participants were receiving methadone at study baseline. Participants were randomly assigned to receive either TDF 300 mg ( n = 1204) or placebo ( n = 1209) and participants could choose to receive study drug as a 28-day supply for self-administration or as daily directly observed therapy. Adherence was determined by direct observation (for those opting for this delivery strategy) or by dried blood spot testing for TDF levels. Risk behavior was repeatedly analyzed to look for evidence of possible risk compensation. Over 9665 person-years of follow-up, there were 17 new HIV infections in the TDF group and 33 new infections in the placebo group. Thus compared with placebo, TDF was associated with a relative risk reduction of HIV infection of 48.9% (95% confidence interval [CI], 9.6%–72.2%; P = .01). Participants with high adherence, categorized as taking the medication at least 71% of prescribed days (approximately 5 days per week), had a 73.5% (95% CI, 16.6–94.0; P = .03) risk reduction. In other subgroup analyses, TDF had higher efficacy in women than men (78.6%; 95% CI, 16.8%–96.7%; P = .03) and in participants aged 40 years or more compared with those aged <40 years (88.9%; 95% CI, 41.1%–99.4%; P = .01). Reported sexual and injecting risk behavior decreased significantly overall during the trial. Side effects were minimal, with the treatment arm experiencing nausea and/or vomiting at a higher rate than the control.

The BTS established the efficacy of TDF in a high-risk population of PWID but has not been replicated to date. There are a number of possible reasons why additional large-scale randomized controlled trials of PrEP have not been conducted among PWID. One is the concern about the ethics of providing PrEP to PWID in settings where other harm reduction tools, such as MAT for opioid use disorder or SSPs, are not available, including in global regions where HIV incidence is rising and is primarily attributable to injection drug use [ ]. The other concern about a randomized controlled trial of PrEP among PWID is that study recruitment would require people to disclose their ongoing injecting behaviors, which is not only highly stigmatized but also criminalized, including in the United States [ ].

Preexposure prophylaxis effectiveness in the “real world”

In the absence of other clinical trials for PrEP efficacy, data from demonstration projects support PrEP effectiveness in the “real world” and can provide guidance on PrEP implementation. For example, in the open-label extension of the BTS, known as BTS-OLE, 798 (60%) of originally enrolled participants chose to continue on PrEP. Those who were aged 30 years or more, injected heroin, or had been incarcerated in prison during the trial more often chose to continue on PrEP, suggesting PrEP might be acceptable to PWID at the highest risk of HIV who would benefit from it the most [ ]. In preliminary outcome data, the HIV incidence rate in participants not on PrEP was 0.7 per 100 person-years compared with 0.5 per 100 person-years in the group on PrEP, yielding a significant protective benefit of PrEP in this high-risk population of PWID [ ]. Although not exhaustive, an updated list of large-scale PrEP demonstration and implementation projects in United States and international settings is maintained online [ ] and on ClinicalTrials.gov for federally funded studies.

Additional evidence for PrEP in PWID is derived from mathematic modeling studies. Published data support the cost-effectiveness of PrEP for PWID, particularly when it is combined with expanded HIV screening strategies and early treatment for those found to have HIV, averting up to 26,700 new infections and reducing HIV prevalence by up to 14% among PWID in the United States [ ]. Another modeling study found that the most cost-effective approach to HIV prevention for PWID combines PrEP for HIV prevention with naloxone for overdose prevention and linkage to addiction treatment [ ]. Sustainable cost-effectiveness of PrEP for PWID depends on pharmaceutical drug pricing and enrollment strategies [ ].

Indications for preexposure prophylaxis in people who inject drugs

Since the FDA approval of TDF/FTC in 2012 and based on data from the BTS, the CDC has developed clinical guidance on PrEP indications for PWID [ ]. Because PWID may experience HIV risk not only from injecting but also related to high-risk sex, PWID may meet PrEP eligibility criteria in one or more categories of risk ( Box 11.1 ).

To assess people for PrEP, healthcare providers need to be prepared to accurately and comprehensively evaluate risk. This requires a nonjudgmental approach to screening in order to foster trust, encourage disclosure, and prevent further stigmatization of PWID. Although the US Preventive Services Task Force does not currently recommend universal screening for PrEP eligibility or HIV, they do recommend that providers prescribe PrEP if they deem patients to be at sufficiently high risk for HIV [ ]. To assess HIV risk, providers should inquire whether patients

• 1.

  have injected any drugs not prescribed to them in the past 6 months;

• 2.

  have shared needles, syringes, or other injecting or preparation equipment (e.g., cotton, “cookers,” syringes for splitting or sharing drugs, etc.);

• 3.

  are on MAT (e.g., methadone, buprenorphine, or naltrexone);

• 4.

  are at short-term risk of relapse to injection or noninjection drug use;

• 5.

  engage in condomless sex with high-risk partners (MSM, PWID, transactional sex, unknown HIV status, HIV+, and not virally suppressed);

• 6.

  have had a recent bacterial sexually transmitted infection (e.g., chlamydia, gonorrhea, or syphilis).

If in the course of a behavioral risk assessment, patients disclose ongoing injection drug use, they should be offered access to harm reduction services (including SSPs and overdose prevention with naloxone) and treatment for opioid use disorder (including MAT if indicated). Per clinical care guidelines, in addition to conducting a behavioral risk assessment, providers should perform baseline HIV testing and phlebotomy for renal function testing. Because PWID often experience housing instability, underinsurance, partner violence, unemployment, and criminal justice involvement, wraparound services need to be in place to address these issues in addition to PrEP provision. PrEP is a program not a drug.

The HIV prevention or preexposure prophylaxis care continuum

The current prevailing model of PrEP delivery parallels the HIV care continuum [ , ]. In this model, patients must first be identified as being “at risk” for HIV infection. This requires an accurate self-perception of personal risk and disclosure of risk behaviors to a possible PrEP provider or referral source. Patients must also test negative for HIV. If patients and their providers are aware of PrEP, they can be linked to PrEP care. Although PrEP services have traditionally been the domain of infectious disease clinicians (who have experience prescribing TDF/FTC as part of a treatment regimen for HIV), PrEP scale-up demands expansion of the pool of potential providers, including to primary care [ ]. A limited pool of potential PrEP providers is especially limiting for PWID [ ]. Because the PrEP care continuum is predicated on patients actively engaging with healthcare providers and traditional systems of care, PWID face several challenges at every step ( Fig. 11.2 ).

Major challenges to PrEP care engagement for PWID in the prevailing model of care include competing priorities, such as co-occurring medical conditions (hepatitis C, sexually transmitted infections), psychiatric conditions, substance use disorders, and social conditions that each require treatment and intervention. If left undiagnosed and/or undermanaged, these conditions can interfere with the ability of PWID to access and be retained on PrEP. Although ideally care for these co-occurring conditions is integrated into PrEP delivery programs, at a minimum, PrEP providers can screen, briefly intervene, and refer to treatment (SBIRT). Perhaps in part because of these barriers to engagement in the PrEP care continuum for PWID, there is a translational efficacy-effectiveness gap in PrEP among PWID. Although an estimated 72,000–115,000 PWID would qualify for PrEP based on current clinical criteria [ ], <1% have actually received it since TDF/FTC was approved as PrEP in 2012 [ ].