Human Immunodeficiency Virus Prevention With Preexposure Prophylaxis in Sexually Transmitted Disease Clinics

Preexposure prophylaxis (PrEP) is an human immunodeficiency virus (HIV) prevention intervention that has been available since the Food and Drug Administration approved the antiretroviral (ARV) medication Truvada for a prevention indication in July 2012, and since the Centers for Disease Control and Prevention (CDC) issued clinical practice guidelines for its use to reduce the risk of acquiring HIV infection for persons at substantial risk in May 2014.1 Clinical trials, demonstration projects, and implementation studies have demonstrated its effectiveness in reducing the risk of HIV acquisition.2–9 Although PrEP has been available for several years, its uptake in the United States has been low but increasing.10,11 Because sexually transmitted diseases (STDs) have been found to be associated with HIV acquisition, they serve as objective markers of HIV risk and can identify STD patients who might benefit from PrEP.12–16 In this article, we aim to increase PrEP awareness among STD health care providers, a group of clinicians who provide prevention services for many persons at substantial risk of HIV acquisition, and we describe models for implementing PrEP in the STD clinic setting. Human immunodeficiency virus prevention efforts, including ARV treatment as prevention and condom promotion, over the past several years have resulted in the incidence of HIV infection remaining stable or decreasing in many US subpopulations.17 Despite these prevention efforts, incidence continues to increase among men who have sex with men (MSM), with the steepest increases among young black MSM.17 Although HIV diagnosis rates decreased among women from 2010 through 2014, 19% of new diagnoses in 2014 were in women, and black women accounted for 62% of these diagnoses.18 Because of high rates of continuing transmission in some populations, it is especially important to target persons in these key populations, such as young MSM and females with high-risk sexual behaviors, for HIV testing with linkage to HIV prevention and care services. Existing disparities in the incidence of HIV infections might worsen if access and utilization of prevention services, such as PrEP, are not targeted for the most-at-risk populations, especially young black MSM.19 PrEP Is Highly Effective for HIV Prevention The availability of PREP as a highly effective biomedical HIV prevention tool initiated a paradigm shift in HIV prevention. Before the availability of PrEP, persons at risk of acquiring HIV infection could only be offered behavioral risk reduction counseling and condoms to protect them against HIV and other STDs. Preexposure prophylaxis offers the potential to halt and reverse the increasing trends we have observed among young MSM over the past several years, and further decrease the downward trend in HIV acquisition among women. Preexposure prophylaxis consists of 2 ARV medications, tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), coformulated as a single pill (Truvada) that is taken once daily.1 In the pre-exposure prophylaxis initiative randomized clinical trial, TDF-FTC was found to reduce the risk of HIV infection in MSM by 44% overall; by 92% among those with detectable peripheral blood mononuclear cells intracellular drug levels5; and by 96% among those with peripheral blood mononuclear cell intracellular drug levels that corresponded to 4 doses per week and by 99% with 7 doses.2 In an open-label randomized trial in England that enrolled MSM, HIV incidence was reduced by 86% among men who immediately initiated PrEP at the time of evaluation compared with those who deferred PrEP initiation for 1 year.9 Clinical trials of PrEP efficacy have also demonstrated decreased acquisition of HIV infection in heterosexual men and women with 62% efficacy7; and HIV-serodiscordant heterosexual couples with 75% efficacy, and 90% among those with detectable levels of tenofovir in their plasma.3 In trials that enrolled persons who inject drugs, PrEP efficacy was 49% overall, and 84% among those with 98% adherence based on daily directly observed treatment.4,20 STDs and Risk for HIV Acquisition Studies have found that persons diagnosed with syphilis, gonorrhea, or chlamydia were at greater risk of acquiring HIV infection than those without these STDs.12–16 Among HIV-uninfected MSM in Baltimore in 2011, the estimated annual HIV diagnosis rate was 3% for all MSM, compared to 5% for MSM with one syphilis infection, and 23% for those with a repeat syphilis infection.16 In New York City from 2000 to 2010, 15% of men diagnosed with syphilis also acquired HIV infection.14 In that study, among all males with primary or secondary syphilis, the mean annual HIV incidence was 3.6%; 4.1% among those with secondary syphilis; 2.6% among those with primary syphilis; and 7.9% among those with another bacterial STD. In another study, HIV-uninfected MSM in New York City with rectal chlamydia or gonorrhea had a significantly higher annual HIV incidence of 6.7% compared with 2.5% among those without rectal infections, and among MSM with rectal infections the annual HIV incidence was 5 times as high among black MSM as MSM in other populations.13 Among MSM in San Francisco diagnosed with rectal chlamydia or gonorrhea, those with more than 1 infection in the previous 2 years were found to be 8 times as likely to acquire HIV infection compared with those without a previous rectal infection.12 Although fewer studies have assessed the association between bacterial STDs and HIV acquisition among women, 1 study found that women in Florida with syphilis or gonorrhea were at the highest risk for a subsequent HIV diagnosis. Women without a bacterial STD had an HIV diagnosis rate of 30 cases per 100,000 person-years of follow-up compared with women with syphilis of 598 per 100,000 person-years, those with gonorrhea of 171 per 100,000 person-years, and those with chlamydia of 66 per 100,000 person-years.15 The increased risk of HIV among persons with STDs can be attributed to several factors. First, STDs serve as an objective biomarker of risk behavior that can put persons at increased risk of acquiring an HIV infection. Risk behaviors, such as condomless sex and multiple sex partners that increase the risk of acquiring an STD, can also result in HIV exposure. Rectal infection with gonorrhea or chlamydia is a marker of unprotected receptive anal intercourse, a sexual behavior that is strongly correlated with HIV seroconversion.21 Second, HIV and bacterial STDs are both highly prevalent in some sexual networks, such as those that include MSM and black women.22 Third, evidence suggests that STDs can increase both the risk of HIV transmission and acquisition,23,24 likely through mechanisms that involve increased viral shedding, inflammatory processes, and mechanical disruption of tissue barriers. STD Clinics Are Ideal Settings for PrEP Implementation Sexually transmitted disease clinics are an important health care setting for PrEP implementation because they are often used by persons in populations that are at increased risk of acquiring an HIV infection. In addition, implementing PrEP more widely in STD clinics could help reduce racial and ethnic disparities in the incidence of HIV, given that STDs disproportionately affect black and Hispanic populations and STD clinics disproportionately provide health care for persons in these populations. In a recent study of persons who sought care in an STD clinic, 49% of male patients were black, 21% Hispanic, and 24% MSM; and 57% of female patients were black and 19% Hispanic.25 This study also found that 50% of persons seeking care in public STD clinics were uninsured, underscoring the importance of STD clinics as an important safety net for HIV testing and prevention. An encounter in the STD clinic is a valuable opportunity to provide HIV testing. Human immunodeficiency virus testing serves as a decision node for either linkage to HIV care services for those whose HIV tests are positive, or risk assessment with PrEP as a prevention option for those whose tests are negative (Fig. 1). However, not all persons who seek STD services or are diagnosed with STDs are at substantial risk of HIV acquisition. The CDC recommends that PrEP be offered to sexually active MSM and heterosexual men and women who have an HIV-infected sex partner. In addition, PrEP is indicated for sexually active MSM with a recent bacterial STD, a high number of sex partners, a history of inconsistent or incorrect condom use, or a history of commercial sex work.1 Preexposure prophylaxis is also indicated for sexually active heterosexual men and women with these risk factors, but with the additional requirement that they live in an area with high HIV prevalence or are part of a high-prevalence network.1 Preexposure prophylaxis indications for persons who inject drugs include those who have an HIV-infected injecting partner, are sharing injection equipment, or who underwent recent drug treatment but are currently injecting.1 In an STD care setting, HIV-negative MSM who report condomless receptive anal intercourse or who were recently diagnosed with syphilis, or rectal gonorrhea or chlamydia, should be assessed for the risk of acquiring HIV infection and offered PrEP if found to be at substantial risk. Sexually active HIV-negative heterosexual men and women with recent syphilis or gonorrhea also might benefit from PrEP. Sexually transmitted disease clinic patients with genital chlamydia or pharyngeal gonorrhea should also be carefully assessed for PrEP indications and offer PrEP if found to be at substantial risk of acquiring HIV infection.Figure 1: Human immunodeficiency virus testing as a decision node for linkage to HIV care with initiation of ARV treatment for HIV-positive persons, and HIV prevention with PrEP for HIV-negative persons who are at substantial risk of acquiring HIV infection.PrEP Health Care Services The CDC recommends that HIV testing be performed before initiating PrEP to confirm that a patient does not have an HIV infection.1 In clinical trials, drug-resistant HIV has developed in persons who initiated PrEP medications with unrecognized acute HIV infection.3–5,7 These patients had negative HIV antibody test results but detectable virus with HIV-1 RNA testing, and many reported nonspecific clinical symptoms of acute HIV infection, such as fever and fatigue. To avoid initiating PrEP during acute HIV infection, clinicians should ask patients about symptoms of acute infection, but because these symptoms are nonspecific, 1 of 3 HIV testing strategies to detect acute infection should also be used. The first option is to use a laboratory-based 4th generation HIV antigen-antibody assay as the HIV test. The fourth-generation assay is recommended by CDC and the Association of Public Health Laboratories as the preferred screening test for HIV diagnosis.26 In addition to detecting HIV antibody, the fourth-generation assay also detects p24 antigen that is present during the acute and early phases of HIV infection. A food and drug administration–approved point-of-care fourth-generation test is available; however, its sensitivity and specificity compared with laboratory-based tests for acute HIV infection has not been well characterized. The second option is to perform HIV-1 RNA testing in addition to HIV antibody testing. The HIV-1 RNA assays are the most sensitive tests for acute HIV infection but they must be performed in a specialized laboratory. If fourth-generation assays or HIV-1 RNA testing are not available, a third option is to perform an HIV antibody test only (either point-of-care or laboratory-based) and if the patient has any symptoms or signs of acute infection then PrEP should be deferred and the patient should be retested in 1 month. In addition, every STD clinic patient should be offered other prevention interventions, such as risk-reduction counseling and provision of condoms.27 Condom use is recommended to prevent against the acquisition of other STDs, including for those who opt for PrEP.1 In addition to confirming HIV-negative status at PrEP initiation, CDC recommends that HIV testing should be performed every 3 months while taking PrEP.1 Also, at follow-up visits, clinicians should assess for symptoms or signs of acute infection in patients taking PrEP and perform prompt diagnostic testing if acute HIV infection is suspected. Testing for creatinine clearance and STDs at baseline is also recommended, with repeat STD testing every 6 months, and repeat creatinine clearance testing 3 months after PrEP initiation and then every 6 months while using PrEP.1 Sexually transmitted disease testing includes syphilis serology and nucleic acid amplification tests for chlamydia and gonorrhea at all reported anatomic sites of sexual exposure (i.e, rectal, vaginal, urethral, and oropharyngeal).1,27 Before initiating PrEP, CDC recommends that HBV and HCV infection status should be documented by serologic screening,1 and that patients found to be susceptible to HBV infection should be offered vaccination. Because TDF-FTC provides effective antiviral treatment of HBV, persons with chronic active hepatitis B infection who discontinue PrEP medications might be at risk of a hepatitis flare from rebound HBV viremia that can result in hepatic damage. Models of PrEP Implementation As PrEP availability increases, models of implementation that are specific for STD clinics are needed. Three models are used to implement PrEP health care services for HIV-negative persons who are identified in STD clinics to be at substantial risk of acquiring an HIV infection (Fig. 2): (1) PrEP services provided in the STD clinic, (2) referral to a PrEP service provider in the community at a different location than the STD clinic, and (3) navigator-assisted linkage to a PrEP service provider in the community at a different location than the STD clinic.Figure 2: Implementation models of PrEP services for STD clinic patients: (A) PrEP services provided in the STD clinic, (B) referral to a PrEP service provider in the community, and (C) active linkage to a PrEP service provider in the community.Model 1: PrEP Services Provided in the STD Clinic Direct provision of PrEP in the STD clinic has several advantages. Sexually transmitted disease clinics serve as centers of sexual health expertise, an important component of PrEP care for persons at sexual risk for HIV acquisition. Sexually transmitted disease clinics offer comprehensive, quality STD services that are integral to PrEP management that might not be available in many primary care settings, such as nucleic acid amplification tests for nongenital chlamydia and gonorrhea screening and syphilis diagnostic and management expertise. Further, STD clinical and counseling staff have a great wealth of experience in discussing sexual health and risk in a culturally competent and nonjudgmental manner. Preexposure prophylaxis implementation would also encourage STD clinics to use fourth-generation HIV testing that can detect acute HIV infection, a laboratory service that is not available in many STD clinics.28 Integrating PrEP with STD services can expedite initiation of PrEP. Baseline PrEP laboratory testing and insurance enrollment can be performed at the encounter for STD care where the patient was assessed and offered PrEP, preventing a possible failure to follow-up for PrEP. A prescription for PrEP can be sent to a pharmacy after discussing laboratory test results with the patient by telephone. For STD clinics that have existing systems to bill third-party payers for clinical services, PrEP services could provide additional revenue to support a sustainable business model for sexual health services. To provide quality PrEP services, STD clinics might consider hiring patient navigators or retraining disease intervention specialists (DIS) to assist patients with scheduling and attending their PrEP appointments, obtaining health insurance or using medication assistance programs to help pay for medication and clinical services, supporting adherence to PrEP medications, and supporting utilization of additional essential services such as behavioral health and social services. Although hired, dedicated patient navigators would not place a burden on existing STD clinical staff, a disadvantage is that ongoing resources are required to support such services. Some STD clinics might encounter barriers to implementing a direct PrEP provision model. Sexually transmitted disease clinics are typically not organized for the longitudinal care of patients who may be on PrEP for several months to years. In addition, busy STD providers might be hesitant to take on the additional responsibilities required for clinical management of PrEP patients at follow-up visits in the STD clinic, or might be unfamiliar with prescribing ARV medications. Although HIV and hepatitis B testing services are supported with public health resources in public STD clinics, creatinine testing is not typically ordered and would require that specimens be sent to a commercial laboratory. Model 2: Referral to a PrEP Service Provider in the Community A second implementation model involves referral to PrEP services provided at a different location than the STD clinic, such as a community health care provider or clinic. To ensure that STD patients have access to PrEP services at the referral site, the STD clinic must maintain an updated list of community PrEP providers along with their locations and the types of insurance that they accept. It would also be helpful to have a formal agreement with 1 or more local PrEP providers to accept STD clinic patients in the PrEP clinic, such as a of The PrEP referral model resources from the STD clinic and a time burden on STD clinic However, this PrEP implementation model has some Some might not have an PrEP as PrEP availability increases, of PrEP providers require and This model that patients use services in a at a different location than the STD clinic, that an be for a and increasing the risk that the patient might not with the PrEP If the PrEP referral is to it is or or it is to not provide quality health the patient might not for PrEP Model to a PrEP Service Provider in the Community A third implementation model is to model but involves the use of patient navigators to assist STD clinic patients with scheduling and attending their first PrEP and if the is to assist with obtaining health insurance to ensure access to the referral As with model the STD clinic might have a formal agreement with the PrEP referral clinic, and the navigators would be of the specific insurance of these Although dedicated patient navigators would not place a burden on existing STD clinical staff, a disadvantage is that ongoing resources are required to support such patient services. services can be provided by existing health whose primary responsibilities include STD and services. Although patient services can be an use of existing health these staff would require specialized the decreased effectiveness of in recent years, it is that the this public health to serve as PrEP navigators might be an for in the of biomedical HIV prevention. Preexposure provided as a clinical has been in health care and found to be effective and to both providers and including in an STD care As part of the PrEP a demonstration PrEP was offered to MSM who used care in an STD clinic in San Among about initiated PrEP with high rates of over the Some PrEP reported from both and providers, underscoring the for of both the of potential and health care Preexposure prophylaxis services provided in a health were also and among persons who initiated PrEP, HIV over person-years of PrEP Preexposure prophylaxis should only be initiated in a clinic where ongoing PrEP care be by a PrEP prescription or medication PrEP in the STD clinic, and then the patient to another health care for ongoing might result in many patients to might encounter barriers to attending visits, such as of or with the referral clinic. prophylaxis that must be provided of a potential HIV the provision of PrEP is not an PrEP is essential for effectiveness and both PrEP initiation and ongoing health care should in the health care Sexually transmitted disease clinic patients who are to an PrEP either by a referral or with and an initiation with the PrEP provider have demonstrated a to PrEP care that might of adherence to follow-up to PrEP Implementation Sexually transmitted disease care providers might several barriers to PrEP that prevent them from it to patients who would benefit from PrEP. are that PrEP is that health insurance might not or for daily for an of However, most commercial health and the of PrEP laboratory testing, and For those who might not have health insurance or insurance the of Truvada offers a medication assistance to help these In addition, STD clinics offer most of the recommended laboratory testing such as HIV testing, STD testing, and baseline hepatitis B testing. These services are typically supported by public health in STD clinics and could be a of after insurance Sexually transmitted disease care providers might have about the safety of ARV for persons who are not In randomized clinical trials of PrEP safety and efficacy, not for persons who TDF-FTC or other and were more in PrEP but the first of PrEP Sexually transmitted disease clinicians might also that ARV medications used for PrEP can be only by an disease or HIV treatment The PrEP and were to primary care clinicians as PrEP and PrEP can be and by and providers in STD clinics using these are available for clinicians as they with PrEP such as for PrEP providers from CDC at and from at The is a clinical service that is provided by PrEP providers and is available of to clinicians who PrEP by or by Sexually transmitted disease care providers might be that persons who take PrEP increase that can increase their risk of acquiring other STDs. Risk with condomless sex or sex with multiple partners might to increased incidence of STDs. Although in condom use have been reported in some PrEP rates of bacterial STDs have not been to be higher while taking PrEP than before its STD screening for PrEP patients provide an opportunity for prompt diagnosis and treatment of any STDs. It is likely that PrEP services STD with PrEP patients more for STDs than persons in other populations who are only Preexposure prophylaxis is a prevention intervention that has been demonstrated in clinical trials and implementation studies to protect against HIV acquisition. To be effective in decreasing the incidence of HIV in a community, PrEP must be targeted at the in the community, including persons who use STD The STD clinic patient is a group at significantly higher risk of HIV acquisition than patient populations found in most primary care This is because they are often from and disproportionately by both HIV and STDs, and because they are a with an STD that serves as a objective marker of HIV risk Preexposure prophylaxis can be in STD care using a health services model that the and resources of the STD clinic. and for direct provision of PrEP or for linkage to a community PrEP provider could be the of an STD clinic, this prevention intervention available to one of the highest risk populations.