Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

Challenges and Solutions to STI Control in the Era of HIV and STI Prophylaxis.

PURPOSE OF REVIEW: This article reviews current efforts to control bacterial sexually transmitted infections (STIs) among HIV pre-exposure prophylaxis (PrEP) users and outlines the opportunities and challenges to controlling STIs within HIV PrEP programs. RECENT FINDINGS: The incidence of STIs continues to rise globally especially among HIV PrEP users, with an estimated 1 in 4 PrEP users having a curable bacterial STI. STIs and HIV comprise a syndemic needing dual interventions. The majority of STIs are asymptomatic, and when testing is available, many STIs occur in extragenital sites that are missed when relying on urine testing or genital swabs. Optimal testing and treatment, including testing for antimicrobial resistance, pose difficulties in high income countries and is essentially non-existent in most low- and middle-income countries. Novel STI primary prevention strategies, like doxycycline post-exposure prophylaxis (PEP) for STI prevention, have proven to be highly efficacious in some populations. A few jurisdictions have issued normative guidelines and position statements for doxycycline PEP; however, clinical standards for implementation and data on public health impact are limited. STI incidence rates are high and rising in sexually active populations. Sexual health programs should leverage the expansion of HIV PrEP delivery services to integrate STI testing, surveillance, and novel STI prevention services.

Urethrocutaneous fistula following VMMC: a case series from March 2013 to October 2019 in ZAZIC's voluntary medical male circumcision program in Zimbabwe.

BACKGROUND: Urethrocutaneous fistula (subsequently, fistula) is a rare adverse event (AE) in voluntary medical male circumcision (VMMC) programs. Global fistula rates of 0.19 and 0.28 per 100,000 VMMCs were reported. Management of fistula can be complex and requires expert skills. We describe seven cases of fistula in our large-scale VMMC program in Zimbabwe. We present fistula rates; provide an overview of initial management, surgical interventions, and patient outcomes; discuss causes; and suggest future prevention efforts. RESULTS: Case details are presented on fistulas identified between March 2013 and October 2019. Among the seven fistula clients, ages ranged from 10 to 22 years; 6 cases were among boys under 15 years of age. All clients received surgical VMMC by trained providers in an outreach setting. Clients presented with fistulae 2-42 days after VMMC. Secondary infection was identified in 6 of 7 cases. Six cases were managed through surgical repair. The number of repair attempts ranged from 1 to 10. One case healed spontaneously with conservative management. Fistula rates are presented as cases/100,000 VMMCs. CONCLUSION: Fistula is an uncommon but severe AE that requires clinical expertise for successful management and repair. High-quality AE surveillance should identify fistula promptly and include consultation with experienced urologists. Strengthening provider surgical skills and establishment of standard protocols for fistula management would aid future prevention efforts in VMMC programs.

Implementation strategies for integrating pre-exposure prophylaxis for HIV prevention and family planning services for adolescent girls and young women in Kenya: a qualitative study.

INTRODUCTION: Across sub-Saharan Africa, ministries of health have proposed integrating pre-exposure prophylaxis (PrEP) for HIV prevention into family planning (FP) services to reach adolescent girls and young women (AGYW); however, evidence on effective implementation strategies is still limited. We conducted a qualitative study of integrated PrEP-FP service implementation at two FP clinics in Kisumu, Kenya. METHODS: From June 2017 to May 2020, the Prevention Options for Women Evaluation Research (POWER) study enrolled 1000 sexually active, HIV-negative AGYW age 16 to 25. Actions taken to implement PrEP were captured prospectively in 214 monitoring and evaluation documents and 15 interviews with PrEP implementers. We analysed data using conventional and directed content analysis, with the latter informed by the Consolidated Framework for Implementation Research (CFIR) and the Expert Recommendations for Implementing Change (ERIC) compilation. RESULTS: POWER deployed a variety of implementation strategies to train and educate stakeholders (e.g., having new providers shadow PrEP providers); develop stakeholder interrelationships (e.g., organizing support teams with protected time to reflect on implementation progress and make refinements); provide technical assistance; and change physical infrastructure and workflow. Although these strategies reportedly influenced contextual factors across four of the five CFIR domains, they primarily interacted with contextual factors relevant to inner setting, especially implementation climate and readiness for implementation. Overall, implementing PrEP proved easier and less labor-intensive at a private, youth-friendly clinic than a public FP clinic, largely because the baseline structural characteristics (e.g., space, workflow) and organizational mission of the former were more conducive to offering AGYW-centered care. Nevertheless, adoption of PrEP delivery among non-study staff at both sites was low, likely due to the widespread perception that PrEP was not within their scope of work. CONCLUSIONS: Some FP clinics may be "lower-hanging fruit" than others for PrEP implementation. Approaching PrEP implementation as a behavioral intervention for FP providers may help ensure that providers have the requisite capability, opportunity, and motivation to adopt the clinical innovation. In particular, PrEP implementers should assess the need for implementation strategies that support providers' clinical decision-making, establish worker expectations and accountability, and address workload constraints. TRIAL REGISTRATION: Clinical Trial Number: NCT03490058 .

A Pilot Evaluation of Expedited Partner Treatment and Partner Human Immunodeficiency Virus Self-Testing Among Adolescent Girls and Young Women Diagnosed With Chlamydia trachomatis and Neisseria gonorrhoeae in Kisumu, Kenya.

BACKGROUND: Expedited partner treatment (EPT) is effective for preventing sexually transmitted infection recurrence, but concerns about intimate partner violence and missed opportunities for human immunology virus (HIV) testing have limited its use in African settings. METHODS: We conducted a pilot prospective evaluation of EPT among adolescent girls and young women (AGYW) accessing HIV preexposure prophylaxis in an implementation project in Kisumu, Kenya. Those with etiologic diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae were treated and given the option of delivering sexually transmitted infection medication and HIV self-test kits to their current sexual partner(s). At enrollment, we assessed their reasons for declining. Three months after they delivered medication and kits to the partner(s), we assessed their reasons for failing to deliver medication and kits to their partner and reported partner's reactions. RESULTS: Between September 2018 and March 2020, 63 AGYW were enrolled. The majority (59/63 [94%]) accepted EPT, and 50 (79%) of 63 partner HIV self-testing (HIVST). Three quarters (46/59) of those accepting EPT returned for the assessment visit with 41 (89%) of 46 successfully delivering medication to 54 partners, of whom 49 (91%) used it. Seventy percent (35/50) who took partner HIVST kits returned for the assessment, with 80% (28/35) reporting providing kits to 40 partners, of whom 38 (95%) used it. Reported barriers to EPT and partner HIVST uptake among women who declined included anticipated fear that their partner could become angry or violent and loss of relationship. CONCLUSIONS: Both EPT and partner HIVST were acceptable despite noted barriers among Kenyan AGYW with etiologic diagnosis of Chlamydia trachomatis/Neisseria gonorrhoeae and their partners.

Enhancing HIV pre-exposure prophylaxis outcomes among Kenyan adolescent girls and young women with a novel pharmacy-based PrEP delivery platform: protocol for a cluster-randomized controlled trial.

BACKGROUND: In Kenya, 65% of sexually active unmarried women use modern contraceptives, a population at increased risk of HIV acquisition compared to other populations. Anchoring HIV prevention services, including pre-exposure prophylaxis (PrEP), to trusted contraceptive delivery settings offers opportunities to efficiently reach this important population. In Kenya, almost half (40%) of women accessing contraception services do so outside traditional healthcare facilities, such as retail pharmacies. Thus, integrating PrEP services into retail pharmacies may increase options for reaching adolescent girls and young women (AGYW) who could benefit from PrEP. Efforts are underway to define care pathways for pharmacy-delivered PrEP services in Kenya, including unsupported and supported models with nurse navigators. METHODS: The AGYW Pharmacy PrEP study is an unblinded 2-arm cluster-randomized controlled trial in Kisumu, Kenya. The objective is to determine the effect that unsupported versus supported pharmacy-delivered PrEP services has on PrEP initiation, persistence, and adherence among AGYW seeking contraception. Twenty retail pharmacies offering pharmacy provider-led PrEP delivery will be randomized 1:1 to either receive or not receive a nurse navigator to support PrEP delivery. Eligible AGYW (n = 1900 total, n = 950/arm) will be ≥ 15 years old, purchasing a method of contraception at the pharmacy. Trained pharmacy provider will offer eligible AGYW either daily oral PrEP or the monthly DPV vaginal ring. The primary trial outcomes are PrEP initiation (use of PrEP at 1 month), persistence (use of PrEP at 10 months), and adherence (quantified by levels of TFV or DPV in hair samples). Additionally, several secondary (STI incidence, PrEP method selection, predictors of PrEP adherence) and exploratory outcomes (HIV incidence, quality of care, contraceptive method mix) will be explored. DISCUSSION: We hypothesize pharmacy-delivered PrEP services supported with nurse navigator, versus delivered by pharmacy providers alone, will improve PrEP outcomes among AGYW seeking contraception. Our results will help policy makers better understand how to potentially implement this novel differentiated service model for PrEP and prime pharmacies for the delivery of new PrEP agents in the pipeline (e.g., long-acting injectables and multi-purpose technologies). The study was initiated on May 13, 2023, and is expected to be completed by February 2025. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05467306), with registration on July 20, 2022.

Measuring the performance of computer vision artificial intelligence to interpret images of HIV self-testing results.

Introduction: HIV self-testing (HIVST) is highly sensitive and specific, addresses known barriers to HIV testing (such as stigma), and is recommended by the World Health Organization as a testing option for the delivery of HIV pre-exposure prophylaxis (PrEP). Nevertheless, HIVST remains underutilized as a diagnostic tool in community-based, differentiated HIV service delivery models, possibly due to concerns about result misinterpretation, which could lead to inadvertent onward transmission of HIV, delays in antiretroviral therapy (ART) initiation, and incorrect initiation on PrEP. Ensuring that HIVST results are accurately interpreted for correct clinical decisions will be critical to maximizing HIVST's potential. Early evidence from a few small pilot studies suggests that artificial intelligence (AI) computer vision and machine learning could potentially assist with this task. As part of a broader study that task-shifted HIV testing to a new setting and cadre of healthcare provider (pharmaceutical technologists at private pharmacies) in Kenya, we sought to understand how well AI technology performed at interpreting HIVST results. Methods: At 20 private pharmacies in Kisumu, Kenya, we offered free blood-based HIVST to clients ≥18 years purchasing products indicative of sexual activity (e.g., condoms). Trained pharmacy providers assisted clients with HIVST (as needed), photographed the completed HIVST, and uploaded the photo to a web-based platform. In real time, each self-test was interpreted independently by the (1) client and (2) pharmacy provider, with the HIVST images subsequently interpreted by (3) an AI algorithm (trained on lab-captured images of HIVST results) and (4) an expert panel of three HIVST readers. Using the expert panel's determination as the ground truth, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for HIVST result interpretation for the AI algorithm as well as for pharmacy clients and providers, for comparison. Results: From March to June 2022, we screened 1,691 pharmacy clients and enrolled 1,500 in the study. All clients completed HIVST. Among 854 clients whose HIVST images were of sufficient quality to be interpretable by the AI algorithm, 63% (540/854) were female, median age was 26 years (interquartile range: 22-31), and 39% (335/855) reported casual sexual partners. The expert panel identified 94.9% (808/854) of HIVST images as HIV-negative, 5.1% (44/854) as HIV-positive, and 0.2% (2/854) as indeterminant. The AI algorithm demonstrated perfect sensitivity (100%), perfect NPV (100%), and 98.8% specificity, and 81.5% PPV (81.5%) due to seven false-positive results. By comparison, pharmacy clients and providers demonstrated lower sensitivity (93.2% and 97.7% respectively) and NPV (99.6% and 99.9% respectively) but perfect specificity (100%) and perfect PPV (100%). Conclusions: AI computer vision technology shows promise as a tool for providing additional quality assurance of HIV testing, particularly for catching Type II error (false-negative test interpretations) committed by human end-users. We discuss possible use cases for this technology to support differentiated HIV service delivery and identify areas for future research that is needed to assess the potential impacts-both positive and negative-of deploying this technology in real-world HIV service delivery settings.

Stand-alone model for delivery of oral HIV pre-exposure prophylaxis in Kenya: a single-arm, prospective pilot evaluation.

INTRODUCTION: The delivery of daily, oral HIV pre-exposure prophylaxis (PrEP) at private pharmacies may overcome barriers to PrEP delivery at public healthcare facilities, including HIV-associated stigma, long wait times and overcrowding. METHODS: At five private, community-based pharmacies in Kenya, a care pathway for PrEP delivery (ClinicalTrials.gov: NCT04558554) was piloted-the first of its kind in Africa. Pharmacy providers screened clients interested in PrEP for HIV risk, then used a prescribing checklist to identify clients without medical conditions that might contraindicate PrEP safety, counsel them on PrEP use and safety, conduct provider-assisted HIV self-testing and dispense PrEP. For complex clinical cases, a remote clinician was available for consultation. Clients who did not meet the checklist criteria were referred to public facilities for free services delivered by clinicians. Pharmacy providers dispensed a 1-month PrEP supply at initiation and a 3-month supply thereafter at a client fee of 300 KES (∼$3 USD) per visit. RESULTS: From November 2020 to October 2021, pharmacy providers screened 575 clients, identified 476 who met the prescribing checklist criteria and initiated 287 (60%) on PrEP. Among pharmacy PrEP clients, the median age was 26 years (IQR 22-33) and 57% (163/287) were male. The prevalence of behaviours associated with HIV risk among clients was high; 84% (240/287) reported sexual partners with unknown HIV status and 53% (151/287) reported multiple sexual partners (past 6 months). PrEP continuation among clients was 53% (153/287) at 1 month, 36% (103/287) at 4 months and 21% (51/242) at 7 months. During the pilot observation period, 21% (61/287) of clients stopped and restarted PrEP and overall pill coverage was 40% (IQR 10%-70%). Nearly, all pharmacy PrEP clients (≥96%) agreed or strongly agreed with statements regarding the acceptability and appropriateness of pharmacy-delivered PrEP services. CONCLUSIONS: Findings from this pilot suggest that populations at HIV risk frequently visit private pharmacies and PrEP initiation and continuation at pharmacies is similar to or exceeds that at public healthcare facilities. Private pharmacy-based PrEP delivery, conducted entirely by private-sector pharmacy staff, is a promising new delivery model that has the potential to expand PrEP reach in Kenya and similar settings.

Measuring the performance of HIV self-testing at private pharmacies in Kenya: a cross-sectional study.

INTRODUCTION: HIV self-testing (HIVST) has the potential to support daily oral pre-exposure prophylaxis (PrEP) delivery in private pharmacies, but many national guidelines have not approved HIVST for PrEP dispensing. In Kenya, pharmacy providers are permitted to deliver HIVST, but often do not have the required certification to deliver rapid diagnostic testing (RDT). We estimated the performance of provider-delivered HIVST compared to RDT, the standard of care for PrEP delivery, at private pharmacies in Kenya to inform decisions on the use of HIVST for PrEP scale-up. METHODS: At 20 pharmacies in Kisumu County, we trained pharmacy providers (pharmacists and pharmaceutical technologists) on blood-based HIVST use and client assistance (if requested). We recruited pharmacy clients purchasing sexual and reproductive health-related products (e.g. condoms) and enrolled those ≥18 years with self-reported behaviours associated with HIV risk. Enrolled clients received HIVST with associated provider counselling, followed by RDT by a certified HIV testing services (HTS) counsellor. Pharmacy providers and clients independently interpreted HIVST results prior to RDT (results interpreted only by the HTS counsellor). We calculated the sensitivity and specificity of pharmacy provider-delivered HIVST compared to HTS counsellor-administered RDT. RESULTS: Between March and June 2022, we screened 1691 clients and enrolled 1500; 64% (954/1500) were female and the median age was 26 years (IQR 22-31). We additionally enrolled 40 providers; 42% (17/40) were pharmacy owners and their median years of experience was 6 (IQR 4-10). The majority (79%, 1190/1500) of clients requested provider assistance with HIVST and providers spent a median of 20 minutes (IQR 15-43) with each HIVST client. The sensitivity of provider-delivered HIVST at the pharmacy was high when interpreted by providers (98.5%, 95% CI 97.8%, 99.1%) and clients (98.8%, 95% CI 98.0%, 99.3%), as was the specificity of HIVST in this setting (provider-interpretation: 96.9%, 95% CI 89.2%, 99.6%; client-interpretation: 93.8%, 95% CI 84.8%, 98.3%). CONCLUSIONS: When compared to the national HIV testing algorithm, provider-delivered blood-based HIVST at private pharmacies in Kenya performed well. These findings suggest that blood-based HIVST may be a useful tool to support PrEP initiation and continuation at private pharmacies and potentially other community-based delivery settings.

The Fidelity of a Pharmacy-Based Oral HIV Pre-Exposure Prophylaxis Delivery Model in Kenya.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) delivery at private pharmacies is a promising new differentiated service delivery model that may address barriers to PrEP delivery at public health care facilities. We measured the fidelity of this model (ie, delivery as intended) in a pilot study in Kenya. SETTING: Five private, retail pharmacies in Kisumu and Thika Counties. METHODS: Trained pharmacy providers delivered PrEP services, including identifying eligible clients, counseling on HIV risk, assessing PrEP safety, testing for HIV, and dispensing PrEP. Pharmacy clients completed surveys that assessed the fidelity of the services received after each visit. Standardized client actors (ie, mystery shoppers) were trained on 4 different case scripts, then made unannounced pharmacy visits, and then completed a 40-item checklist that assessed the fidelity and quality of service delivery components. RESULTS: From November 2020 to December 2021, 287 clients initiated and 159 (55%) refilled PrEP. At initiation, most clients were counseled on PrEP adherence (99%, 284 of 287) and potential side effects (97%, 279 of 287) and all received provider-assisted HIV self-testing before PrEP dispensing (findings consistent across refill visits). Nine standardized client actors completed 15 pharmacy visits. At each visit, most actors were asked about their behaviors associated with HIV risk (80%, 12/15) and all were counseled on PrEP safety and side effects. All actors reported that pharmacy providers treated them with respect. CONCLUSIONS: In this first pilot study of pharmacy-delivered PrEP services in Africa, the fidelity of service delivery was high, suggesting that trained providers at private pharmacies can deliver quality PrEP services.