The science of human immunodeficiency virus (HIV) prevention has had several major breakthroughs in recent years, making the once-fantastic goal of HIV eradication suddenly more achievable. Daily oral emtricitabine/tenofovir disoproxil fumarate (Truvada) as preexposure prophylaxis (PrEP) to prevent HIV acquisition is chief among these advances. Preexposure prophylaxis has proven to be safe and effective, with protection approaching 100% among individuals who take on average only 4 pills a week.1 Although patient demand for this new method of HIV prevention is increasing among certain populations in the United States, many clinicians and clinics are struggling to make this service available to patients at greatest risk of HIV infection. The Centers for Disease Control and Prevention recently suggested that about 1.25 million Americans have indications for PrEP,2 yet it is estimated that less than 30,000 people in the United States are currently using PrEP.3
Two specific concerns have limited more widespread enthusiasm for PrEP: imperfect patient adherence, leading to potential drug resistance in those who acquire HIV in a setting of intermittent PrEP use; and patient risk compensation, resulting in less condom use and increased transmission of other sexually transmitted diseases (STD). Several large studies have recently addressed these fears. Among men who have sex with men (MSM) enrolled in a recent large PrEP demonstration project, the majority (>85%) demonstrated drug adherence, with highest adherence seen in individuals reporting riskier sexual behavior.4 However, this reassuring finding is balanced by several studies showing low rates of condom use in patients on PrEP. In the same PrEP demonstration study, about 65% of study participants reported engaging in condomless receptive anal sex and incidence of non-HIV STD was high (90 per 100 person-years). In the Kaiser PrEP cohort, about 28% of participants acquired 1 or more STD during study follow-up.5 However, a direct link between PrEP use and increases in non-HIV STD has not been demonstrated.
In this issue of Sexually Transmitted Diseases, Golden and colleagues6 discuss the PrEP guidelines for the greater Seattle area. Informed by local data and guided by international recommendations, they outline a 2-tiered system designed to guide clinicians in discussions of PrEP. In these guidelines, they advise that providers recommend PrEP to highest-risk patients who are estimated to have greater than 3% annual risk of HIV infection and discuss PrEP with patients estimated to be at elevated risk but less than 3% annual risk of HIV infection. Specifically, these guidelines advise providers to recommend PrEP to any man or transgender person reporting sex with men who, within the last 12 months, have had a diagnosis of rectal gonorrhea or early syphilis; have used methamphetamines or nitrites; have exchanged sex for money or drugs; or are in a sexual relationship with a nonvirologically suppressed HIV-infected person.
Access to PrEP requires that it be available, convenient, and affordable. In many settings, these criteria are not being met. A patient seeking PrEP may encounter a provider who is either unaware of the intervention or unwilling to prescribe it. A 2015 national survey of US health care providers found that one third of primary care providers were not aware of PrEP7; those that are aware of the intervention may not feel comfortable prescribing it or even taking a sexual history to determine eligibility. Meanwhile, patient demand is on the rise. The dramatic increase in patient awareness was highlighted by the findings of a survey at the Seattle Pride Parade8: although only 13% of high-risk HIV-negative MSM reported hearing of PrEP in 2012, over 85% reported having heard of PrEP in 2015.8
Sexually transmitted diseases clinics offer key opportunities for implementation of high-impact PrEP programs. Many HIV-uninfected patients presenting to these clinics meet the criteria of “highest risk” that is outlined in the recommendations by Golden and colleagues. Among 26 US STD clinics collaborating in the CDC STD Surveillance Network, consistently high rates of early syphilis, chlamydia, and gonorrhea were found among HIV-uninfected MSM.9 Men who have sex with men in New York City were recently shown to have a greater than 5% risk of HIV infection in the year after a diagnosis of primary or secondary syphilis.10 The high prevalence of STD among patients eligible for PrEP emphasizes the opportunity and importance of simultaneous implementation of STD screening/treatment and PrEP services.
Although STD clinics pose a unique opportunity for high-impact PrEP implementation, these clinics often have several barriers to implementing PrEP services. Truvada remains an expensive medication, and being on PrEP requires regular laboratory testing for renal disease and HIV/STD screening every three months. Traditionally, STD clinics have not been designed for primary care delivery, and as such are often not equipped with billing systems, electronic medical records, or pharmacy networks. Although financial resources for PrEP are becoming increasingly available via expanded insurance coverage, discount programs, and statewide initiatives, these systems are dynamic and complex. Many STD clinics are understaffed and underfunded, without the resources needed to efficiently navigate patients through complex financial structures.
When discussing PrEP in the context of STD clinics, it is useful to consider a spectrum of engagement in PrEP care as is now widely used in HIV prevention.11 Thus, the PrEP “cascade” is a practical description of what fraction of PrEP-eligible patients is identified as at-risk, aware of and interested in taking PrEP, able to access healthcare, receive a PrEP prescription, and adhere to the medication.12 Most STD clinics that currently promote PrEP focus on the initial steps in the cascade, using a model in which individuals eligible for PrEP are identified in the STD clinic and then referred to another clinic location for PrEP services.
Although relatively easy to implement in STD clinics, this referral model may result in high rates of patient dropout. In the primary STD clinic in Denver, only about 5% of patients considered eligible for PrEP in 2015 by CDC standards13 ultimately accessed PrEP services at the main referral clinic and filled at least 1 prescription for Truvada (G.M., unpublished data). In the active referral program at the Chicago Department of Public Health STD Clinics, providers referred 141 high-risk patients to community PrEP providers from September 2014 to September 2015. Of these, only 45 (32%) ultimately received a prescription for PrEP. Three HIV seroconversions occurred in the interval between referral and PrEP intake (R.B., unpublished data).
Recognizing the low rate of PrEP uptake associated with the referral model, alternative approaches should be explored. STD clinics have long been leaders in providing diagnosis and treatment at the time of visit and some STD clinics that also provide family planning services have initiated same-day long-acting reversible contraception placement as well. Thus, in a similar approach, offering same-day Truvada “starter packs” in the STD clinic could offer protection during the interval time of patient referral to PrEP services. Although it is argued that STD clinics lack the continuity of care needed for ongoing PrEP services, some STD clinics have continuity programs for family planning and should be able to build on this model for the provision of PrEP. Also, a considerable number of STD clinics now have advanced electronic medical record systems and some have started to bill for services, thus removing additional barriers to offering ongoing PrEP in the STD clinic environment.
Preexposure prophylaxis can become a major weapon in the HIV prevention armamentarium if we are able to provide an effective linkage to PrEP services. STD clinics serve patients at very high risk for HIV infection and can play an important role in the PrEP continuum. Challenges will remain, but rather than cause resignation, they should inspire to develop innovations in settings where PrEP can make a big difference.
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13. US Public Health Service. Pre-exposure prophylaxis for the prevention of HIV infection in the United States—2014: a clinical practice guideline. CDC 2014: 1–67.