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.

The Effect of Stigma on Family Planning and HIV Pre-exposure Prophylaxis Decisions of Young Women Accessing Post-Abortion Care in Kenya.

Adolescent girls and young women (AGYW) in Eastern and Southern Africa face parallel epidemics of unintended pregnancy and HIV. Their sexual health decisions are often dominated by intersecting stigmas. In an implementation science project integrating delivery of daily, oral pre-exposure prophylaxis (PrEP) for HIV prevention into 14 post-abortion care (PAC) clinics in Kenya, we enrolled a subset of PrEP initiating AGYW (aged 15 to 30 years) into a research cohort. Utilizing log binomial models, we estimated the effect of PrEP stigma on PrEP continuation (measured via self-report and urine assay for tenofovir) and abortion stigma on contraceptive initiation. Between April 2022 and February 2023, 401 AGYW were enrolled after initiating PrEP through their PAC provider, of which 120 (29.9%) initiated highly-effective contraception. Overall, abortion and PrEP stigmas were high in this cohort. Abortion stigma was more prevalent among those that were adolescents, unmarried, and reported social harm. Among 114 AGYW returning for the month 1 follow-up visit, 83.5% reported continuing PrEP and 52.5% had tenofovir detected. In this subset, higher levels of PrEP stigma were significantly associated with greater likelihood of PrEP adherence, but not PrEP continuation. For abortion stigma, greater scores in the subdomain of isolation were significantly associated with greater likelihood of initiating a highly-effective contraception, while greater scores in the subdomain of community condemnation were significantly associated with reduced likelihood of initiating a highly-effective contraception. Given the burden of stigma documented by our work, PAC settings are a pivotal space to integrate stigma-informed counseling and to empower young women to optimize contraceptive and PrEP decisions.

Structural influences on delivery and use of oral HIV PrEP among adolescent girls and young women seeking post abortion care in Kenya.

Background: Adolescent girls and young women (AGYW) in East and southern Africa experience a disproportionate burden of HIV incidence. Integrating HIV pre-exposure prophylaxis (PrEP) within existing programs is a key component of addressing this disparity. Methods: We evaluated an oral PrEP program integrated into post-abortion care (PAC) in Kenya from March 2021 to November 2022. Technical advisors trained staff at PAC clinics on PrEP delivery, abstracted program data from each clinic, and collected data on structural characteristics. Utilizing a modified Poisson regression, we estimated the effect of structural factors on the probability of PrEP offer and uptake. Findings: We abstracted data on 6877 AGYW, aged 15-30 years, across 14 PAC clinics. PrEP offers were made to 57.4% of PAC clients and 14.1% initiated PrEP. Offers were associated with an increased probability at clinics that had consistent supply of PrEP (relative risk (RR):1.81, 95% CI: 1.1-2.95), inconsistent HIV testing commodities (RR: 1.89, 95% CI: 1.29-2.78), had all providers trained (RR: 1.65, 95% CI: 1.01, 2.68), and were public (RR: 1.89, 95% CI: 1.29-2.78). These same factors were associated with PrEP uptake: consistent supply of PrEP (RR: 2.71, 95% CI: 1.44-5.09), inconsistent HIV testing commodities (RR: 2.55, 95% CI: 1.39-4.67), all providers trained (RR: 2.61, 95% CI: 1.38-4.92), and were public (RR: 2.55, 95% CI: 1.39-4.67). Interpretation: Greater success with integration of HIV prevention into reproductive health services will likely require investments in systems, such as human resources and PrEP and HIV testing commodities, to create stable availability and ensure consistent access. Funding: PrEDIRA 2 was supported by funding from Children's Investment Fund Foundation (R-2001-04433). Ms. Zia was funded by the NIH Ruth L. Kirchstein pre-doctoral award (5F31HD105494-02) and Dr. Heffron was funded by National Institute of Mental Health (K24MH123371).

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.

Qualitative Analysis Using Social Maps to Explore Young Women's Experiences With Social Support of their Oral PrEP Use in Kenya and South Africa.

ABSTRACT: Daily oral pre-exposure prophylaxis (PrEP) adherence is challenging. We explored African adolescent girls and young women's (AGYW) perceptions of the social influencers of their PrEP use and the social influencers' PrEP knowledge and support (six focus group discussions; 33 South African and Kenyan AGYW) in the Prevention Options for Women Evaluation Research demonstration project. Participants completed a social mapping exercise indicating strength and direction of influence of members in their social networks. Mothers and counselors were identified as positive influencers and most influential by >50% of participants, sex partners were labeled negative influencers or both positive and negative, and best friends were mostly positive influencers. HIV- and PrEP-related stigma were the major reasons influencers were identified as negative. Participants wanted their social networks to be better educated about PrEP by someone other than the AGYW themselves (e.g., clinic staff) and to support their PrEP use. To improve PrEP adherence, community- and peer-based PrEP sensitization and delivery interventions should be evaluated.

Provider-client rapport in pre-exposure prophylaxis delivery: a qualitative analysis of provider and client experiences of an implementation science project in Kenya.

Daily oral pre-exposure prophylaxis (PrEP) is being incorporated into services frequented by adolescent girls and young women (AGYW) in sub-Saharan Africa who are at a significant risk of HIV. In non-PrEP studies, positive provider-client rapport has been shown to improve patient decision-making and use of medication in clinical care. We examined AGYW and healthcare provider (HCP) perspectives on the value of and strategies for building positive provider-client rapport. We conducted in-depth interviews from January 2018 to December 2019 with 38 AGYW and 15 HCPs from two family planning clinics in Kisumu, Kenya where PrEP was being delivered to AGYW as part of the Prevention Options for Women Evaluation Research (POWER) study. We used semi-structured interview guides and audio-recorded interviews with participant consent. Verbatim transcripts were analysed using thematic content analysis. HCPs and AGYW emphasised the importance of positive provider-client rapport to meet AGYW support needs in PrEP service delivery. HCPs described how they employed rapport-building strategies that strengthened AGYW PrEP uptake and continuation, including: (1) using friendly and non-judgmental tones; (2) maintaining client confidentiality (to build client trust); (3) adopting a conversational approach (to enable accurate risk assessment); (4) actively listening and tailoring counselling (to promote client knowledge, skills, and self-efficacy); and (5) supporting client agency. Positive provider-client relationships and negative experiences identified in this analysis have the potential to facilitate/deter AGYW from using PrEP while at risk. The strategies to enhance provider-client rapport identified in this study could be integrated into PrEP provider training and delivery practices.

PrEP use and HIV seroconversion rates in adolescent girls and young women from Kenya and South Africa: the POWER demonstration project.

INTRODUCTION: HIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre-exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale-up. METHODS: POWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV-negative AGYW ages 16-25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow-up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan-Meier survival analysis among AGYW with a month 1 visit, defining non-persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV-DP) levels. RESULTS: From June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post-PrEP initiation follow-up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV-DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person-years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV-DP levels indicated <4 doses/week in the prior 6 weeks. CONCLUSIONS: In this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months.  Strategies are needed to simplify PrEP delivery, support adherence and offer long-acting PrEP options to improve persistence and HIV protection.

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.

Cost of pre-exposure prophylaxis delivery in family planning clinics to prevent HIV acquisition among adolescent girls and young women in Kisumu, Kenya.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is increasingly being implemented in sub-Saharan Africa. Adolescent girls and young women (AGYW) in Kenya contribute more than half of all new infections among young people aged 15-24 years, highlighting the need for evidence on the cost of PrEP in real-world implementation to inform the budget impact, cost-effectiveness, and financial sustainability of PrEP programs. METHODS: We estimated the cost of delivering PrEP to AGYW enrolled in a PrEP implementation study in two family planning clinics in Kisumu county, located in western Kenya. We derived total annual costs and the average cost per client-month of PrEP by input type (variable or fixed) and visit type (initiation or follow-up). We estimated all costs as implemented in the study, and under implementation by the Kenyan Ministry of Health (MoH), both at the program volume observed and if the facilities were delivering PrEP at full capacity (scaled-MoH). RESULTS: For the costing period between March 2018 and March 2019, 615 HIV-negative women contributed 1,128 (502 initiation and 626 follow-up) visits. The average cost per client-month of PrEP dispensed per study protocol and per the MoH scenario was $28.92 and $14.52, respectively. If the MoH scaled the program so that facilities could see PrEP clients at capacity, the average cost per client-month of PrEP was $10.88. Medication costs accounted for the largest proportion of the total annual costs (48% in MoH scenario and 65% in the scaled-MoH scenario). CONCLUSIONS: Using data from a PrEP implementation program, we found that the cost per client-month of PrEP dispensed is reduced by 62% if PrEP delivery at the two clinics is scaled up by the MoH. Our findings are valuable for informing local resource allocation and budgetary cost projections for scale-up of PrEP delivery to AGYW. Additionally, previous cost-effectiveness studies have been limited by the use of fixed assumptions of the cost of PrEP per person-month. Our study provides cost estimates from practical data which will better inform cost-effectiveness and budget impact analyses.