Preexposure prophylaxis (PrEP) represents a major breakthrough in HIV prevention, with multiple studies1–3 supporting high rates of efficacy with adherence to tenofovir-emtricitibine. Despite this, PrEP uptake in high-risk groups remains low. Over 1.2 million Americans, including nearly half a million men who have sex with men (MSM), meet the criteria,4 far outnumbering the estimated total of only 79,684 PrEP prescriptions written from 2012 to 2015.5 Moreover, only 7.6% of PrEP prescriptions were for youth younger than 25 years,6 despite this group accounting for 22% of new US HIV infections.7 Similarly, 10% of prescriptions were for blacks,6 a population which represents nearly 50% of new infections.7
Sexually transmitted infection (STI) clinics represent ideal settings for increasing PrEP uptake because they reach persons at high risk for HIV.8–11 Data from New York City’s STI clinics demonstrated an annual HIV incidence of 6.7% in MSM diagnosed with rectal gonorrhea and/or chlamydia12 and strong associations between any incident bacterial STI and new HIV diagnoses.11–13 Further, those most at-risk for HIV, including youth and ethnic minority MSM, may be less likely to have a primary health care provider and continue to use safety net services like public STI clinics,14 even in the era of expanded medical coverage.15 Most STI clinics also routinely offer HIV testing, which is important to identify HIV-negative persons for whom prophylaxis is appropriate.
Preexposure prophylaxis engagement in the STI clinics represents a full spectrum of activities from passive knowledge transfer (eg, with brochures or videos) to on-site PrEP provision.9 A recent demonstration project of MSM and transgender women receiving PrEP in urban STI clinics reported promising results, with high adherence and no new infections among those with therapeutic drug levels,16 suggesting that PrEP engagement can successfully occur in these settings. However, most public STI clinics do not have the resources to implement a full-scale program, which would include monitoring laboratory tests (eg, creatinine clearance), counseling, and providing medication out of the scope of traditional STI services.9,10 In addition, many STI clinics may lack clinical expertise for PrEP provision.17 Alternative real-world models for PrEP engagement that subvert these limitations yet go beyond passive knowledge transfer are needed.
The Chicago Department of Public Health (CDPH) maintains 5 STI clinics which had approximately 20,000 patient visits in 2016. We developed a PrEP active referral mechanism, in which at-risk patients were given a “warm hand-off” to PrEP partner sites in the community. In this report, we describe outcomes of this implementation model framed in the context of an adapted PrEP continuum.
MATERIALS AND METHODS
The CDPH STI Clinics accept walk-in patients aged 12 years and older for no-cost STI/HIV testing and STI treatment. Patients eligible for PrEP active referral were HIV-negative (based on on-site rapid testing or patient self-report) and met one or more of the following criteria as determined by a CDPH STI Clinic practitioner during the visit: (1) cis-woman or MSM with syphilis or rectal gonorrhea or chlamydia, (2) trans-woman, (3) partner of an HIV-positive individual, (3) sex worker, (4) injection drug user, or (5) practiced condomless receptive anal intercourse. Patients not meeting these criteria but expressing interest in PrEP were also considered eligible. After providing basic PrEP information and obtaining consent, CDPH staff securely communicated patient contact information to 1 of the 4 PrEP partner sites selected by the patient. Staff at partner sites would attempt to contact the patient within 72 hours to make a PrEP appointment. Department of Health staff followed up with partners monthly to determine if successful contact (eg, speaking with or receiving a text response from the patient), linkage to a PrEP provider (eg, completing the first PrEP appointment), and prescription of PrEP occurred.
This is a retrospective analysis of all active referrals initiated from CDPH STI Clinics from June 1, 2015, to May 31, 2016. For patients with more than 1 referral during this period, only the first referral was included. Demographics and indications for active referral were extracted from the charts. Data on successful contact, linkage, and PrEP prescriptions were obtained from partner sites. We allowed for 3 months of follow-up from date of consent for each outcome (contact, linkage, and prescription).
Data were analyzed using bivariate and time to event methods. All participants were assigned binomial outcomes of whether they were successfully contacted by the PrEP partner, whether they were linked to a PrEP provider, and whether they received a PrEP prescription. Bivariate analyses using logistic regression assessed associations between the various outcomes of interest and the following covariates: gender, MSM status, age, race/ethnicity, STI referral clinic, PrEP partner clinic, and PrEP eligibility criteria, which was treated as a binomial variable (presence or absence of a bacterial STI, defined as syphilis or rectal gonorrhea or chlamydia).
Time to event analyses were completed using Kaplan-Meier and Cox proportional hazard modeling methods. A successful event was defined as receiving a PrEP prescription. Those who dropped out before receiving a PrEP prescription were censored. Time to event was measured in days, starting with the date of the STI clinic appointment at which active referral consent was obtained. Individuals who dropped out between the STI clinic appointment and contact by a PrEP partner were assigned a censored time to event value of 1 day. Survival distributions were assessed for all covariates described above, and significance (p < 0.05) was determined via the Wilcoxon test. Crude hazard ratios for covariates associated with receiving a PrEP prescription were obtained using Cox proportional hazard models. Two participants who received a PrEP prescription were excluded from time to event analyses because the date of prescription receipt was unknown. All analyses were done using SAS v. 9.4 (Cary, NC). This project was approved by the CDPH Institutional Review Board.
A total of 137 patients were actively referred. The majority (n = 126, 92%) were MSM, mean age was 29 years (SD = 8.4), 52 (38%) were non-Hispanic black, and 44 (32%) were Hispanic (Table 1). Approximately 15% had more than 1 indication for referral, and half (n = 69) had a bacterial STI, including 20 (15%) with rectal chlamydia, 22 (16%) with rectal gonorrhea, and 37 (27%) with syphilis.
Of the 137 who consented, 98 (72%) were successfully contacted by the PrEP partner, 43 (31%) were linked to a PrEP provider, and 40 (29%) received a PrEP prescription (Fig. 1). The percent drop-out was 28% between consent and contact, 40% between contact and linkage, and 2% between linkage and receipt of prescription. In the bivariate analysis, individuals aged 25 years and older were more likely to link (odds ratio [OR], 3.10; 95% confidence interval [CI], 1.30-7.41) and receive a PrEP prescription (OR, 2.70; 95% CI, 1.12–6.45) compared with individuals 24 years and younger (Table 2). Preexposure prophylaxis partner site was the only other covariate significantly associated with successful linkage and prescription (data not shown). There were no covariates associated with successful contact by a PrEP partner site.
The average time between each step in the continuum is shown in Figure 1. Among those who were successfully contacted, the average time from consent to contact was 2.6 times longer for those who dropped out before linkage compared with those who ultimately received a prescription (data not shown). Subgroup analyses revealed that the average time between each step was greater for those 24 years and younger compared with those aged 25 years and older for all steps (Fig. 2).
Time to event analyses revealed that those aged 25 years and older were significantly more likely to receive a PrEP prescription compared with those aged 24 years and younger (hazard ratio, 3.62; 95% risk limits, 1.47–8.92; Table 3, Figs. 3A–B). Preexposure prophylaxis partner site was the only other covariate also significantly associated with receiving a PrEP prescription (data not shown). Among all those who ultimately received a prescription, average time from consent to prescription was 1.7 times greater in those aged 24 years and younger (n = 8) compared with those aged 25 years and older (n = 30) (data not shown).
In 1 year, 137 CDPH STI Clinic patients consented to the PrEP active referral program, of which 72% were contacted, 31% were linked, and 29% ultimately received a PrEP prescription. We observed attrition at all steps, in particular prior to contact and to linkage, which is consistent with findings from other public STI clinic PrEP referral programs. Chan et al18 reported that of 130 MSM interested in PrEP at the Rhode Island STD Clinic, 53% were successfully contacted by clinic staff, 21% linked, and 19% received a prescription. In 2015, the Denver Public Health STI Clinic saw nearly 10,000 unique individuals, 1301 of whom had indications for PrEP. Of those, 177 individuals (14%) were actively referred to a PrEP Linkage-to-Care Coordinator during the STI clinic visit, 83 (47% of those referred) completed a PrEP intake visit, and all individuals with PrEP intake visits received prescriptions (S. Rowan, personal communication, May 10, 2017). Taken together, these observations suggest that once linked, most STI clinic patients go on to receive PrEP prescriptions. Further, the steps upstream of linkage pose the highest risk for drop-out; this could be due to unmeasured variables, including social desirability bias to accept referral, discomfort with providers outside the Department of Health, and structural barriers (eg, transportation). Facilitating or consolidating these steps may mitigate early drop-out. On-site PrEP in the STI clinic may obviate concerns about outside providers and transportation to another site. Yet, the Rhode Island experience suggests that drop-out before linkage is still high (79%) when the on-site PrEP appointment is scheduled 1 to 2 weeks after the initial visit.18 Same day, on-site PrEP appointments within the STI clinic, which would fully consolidate consent, contact, and linkage steps, may lead to enhanced uptake. A model in which STI clinics provide PrEP starter packs at the same day visit, further consolidating medication provision with initial upstream steps, has also been proposed. Resource-intensive models such as these must be balanced against an increasingly challenging funding environment for public STI clinics; additional real-world implementation research focusing on optimal PrEP delivery models in the STI clinic setting is needed.
The PrEP continuum may provide a framework for implementation in STI clinics. Our real-world STI clinic data are consistent with results from an observational study of US HIV-negative MSM which demonstrate dramatic losses at early stages of PrEP engagement.19 Yet, many proposed PrEP cascades are rooted in the HIV care continuum20 and emphasize downstream steps (eg, retention and adherence) while broadly conceptualizing a “catch all” proximal step of PrEP awareness, interest, and/or knowledge.10,21,22 Observational studies of STI clinic patients have also focused on steps downstream of PrEP prescription.23 A recently published Motivational PrEP Cascade for MSM emphasizes behavior change and at least three distinct steps before linkage: precontemplation, contemplation, and PrEParation.19 Similar in depth characterization of the prelinkage steps specific to the STI clinic setting is needed to identify discrete opportunities for intervention and enhanced downstream progression along the PrEP continuum.
Consistent with other studies, this project demonstrates that STI clinics have the potential to reach persons at risk for HIV who are interested in accessing PrEP services through the STI clinic setting.18,24 The majority of this cohort was non-white, MSM, and younger than 35 years of age, which represents the epidemiology of new HIV infections in Chicago25 and the United States.7 Given underutilization of PrEP by vulnerable groups, such as youth and blacks,6 STI clinics should be more frequently leveraged as key PrEP access points for these populations.
We found that youth 24 years and younger were approximately three times less likely to link and receive a PrEP prescription compared with older participants. Further, we found that youth took longer, on average, at each step in the active referral continuum, and those who did successfully receive a prescription took almost twice as long from initial consent to do so compared with those 25 years and older. Consistent with these findings, other studies have shown poor PrEP awareness,26 use,26 and adherence27,28 in young MSM. HIV testing, the gateway to HIV prevention and PrEP, is also underutilized in young MSM29–31; taken together, these data suggest that youth may be at elevated risk for attrition across the entire PrEP continuum, from initial steps to adherence and retention. Lack of access to care and concerns over insurance and confidentiality can be prohibitive to young MSM needing HIV testing31; these may similarly hinder access to PrEP. In addition, youth living with HIV have been identified as vulnerable to drop-out across the HIV treatment continuum.29,32,33 Barriers to HIV care described in youth living with HIV (eg, mental health issues, substance use, stigma, lack of transportation34) may also be relevant for PrEP engagement in this group. Understanding the unique needs of youth across the PrEP continuum is critical given the substantial burden of new infections and observed disparities in PrEP uptake in this population.6 Developing tailored PrEP care to address barriers28 and enhance rapidity of progression along the PrEP continuum for youth is needed.
This report has several limitations. First, the small sample size may have limited our power to detect significant differences and the generalizability of findings to other STI clinics; in addition, the active referral model may not be applicable to STI clinics that lack a network of nearby community PrEP providers. Second, upstream (eg, PrEP awareness) and downstream (eg, PrEP initiation, retention, and adherence) steps in the cascade were not measured. Third, the total number of PrEP-eligible individuals and proportion who consented were also not known, limiting the generalizability of the consenting subgroup to all PrEP-eligible persons seen in the clinics. Finally, potential facilitators and barriers to progressing along each step (eg, insurance status, contact method) were not systematically captured. Nevertheless, this report addresses a need for literature on real-world implementation in resource-limited public STI clinic settings.
In summary, these data demonstrate that a PrEP active referral mechanism from public STI clinics to PrEP partner sites is feasible and reaches high-risk individuals. Further work addressing barriers to linkage, particularly among youth, is needed to optimize engagement along the PrEP continuum.
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