Family influences on oral PrEP use among adolescent girls and young women in Kenya and South Africa.

INTRODUCTION: Effective use of oral HIV pre-exposure prophylaxis (PrEP) has been lower among African adolescent girls and young women (AGYW) than among older women, young men who have sex with men, and serodiscordant heterosexual couples in the region. Efforts to build PrEP support have centered around peers and male partners, but the family may also play an important role. This qualitative study aimed to describe family influence on PrEP use among AGYW in in three African cities. METHODS: POWER (Prevention Options for Women Evaluation Research) was a PrEP demonstration project among 2550 AGYW (16-25 years old) in Johannesburg and Cape Town, South Africa and Kisumu, Kenya conducted from 2017 to 2020. In-depth interviews and focus group discussions were conducted with 136 AGYW participants to explore their PrEP views and experiences, including awareness and interest in PrEP; barriers and facilitators to uptake and use; the influence of family, peers, intimate partners, and community; and the key types of support for their PrEP use. Transcripts were coded and analysed thematically. RESULTS: The decision to initiate PrEP was associated with fear and anxiety linked to anticipated stigma from family members, and with family's lived HIV experience. Family disclosure, especially to mothers, was important to participants, as most lived with their families and considered it essential for them to obtain their mother's approval to use PrEP. Most family members, particularly mothers, provided instrumental, emotional, informational and appraisal support to participants using PrEP, including reminders, encouragement, and problem-solving. Participants reported that family members with insufficient information about PrEP safety and efficacy and who voiced concerns were a substantial barrier to their use. However, they often became supportive after receiving more PrEP information. CONCLUSION: Families, particularly mothers, can play an important role in supporting PrEP use. PrEP programmes should leverage family support to help with PrEP persistence by providing basic information to families about PrEP safety and efficacy. AGYW using PrEP should be encouraged to selectively disclose PrEP use to build support and counseled on how to disclose and address family concerns.

A decision support tool has similar high PrEP uptake and increases early PrEP persistence in adolescent girls and young women in South Africa: results from a randomized controlled trial.

INTRODUCTION: African adolescent girls and young women (AGYW) have high rates of HIV acquisition and are a priority population for HIV pre-exposure prophylaxis (PrEP). PrEP implementation has been limited by AGYW's low perceived HIV risk and provider demands. A decision support tool (DST) with information about PrEP could improve clients' risk perception, knowledge about PrEP, informed decision-making and motivation to use PrEP based on their risk, facilitating PrEP delivery in primary healthcare (PHC) clinics. METHODS: We designed MyPrEP, a client-facing DST about PrEP and HIV prevention, with youth-friendly information and images. The impact of the MyPrEP tool was assessed among HIV-negative women aged 18-25 years presenting to a PHC clinic in Johannesburg, South Africa from March 2019 to 2020. AGYW were randomized by day to the DST or a general health website as the control condition. A clinician blinded to DST versus control allocation provided standard of care counselling about PrEP, offered PrEP, administered a questionnaire and conducted sexually transmitted infection testing. The primary outcome was PrEP initiation and the secondary outcome was PrEP persistence at 1 month, determined by pharmacy dispensation records. RESULTS: Of 386 AGYW screened, 353 were randomized (DST n = 172, control n = 181) with a median age of 21 years (interquartile range [IQR] 20, 23) and 56% (199/353) attending the clinic for HIV testing, 46% (164/353) using contraception, 15% (53/353) using condoms consistently and 37% (108/353) with a curable sexually transmitted infection. PrEP was initiated by 97% in the DST group and 94% in the control group (OR 1.79; 95% confidence interval, CI = 0.79-1.53), of whom two-thirds planned to continue PrEP until they decided if they liked PrEP. At 1 month, PrEP persistence was 19% in the DST and 10% in the control group (OR 1.97, 95% CI 1.08-3.69). Ninety-nine percent randomized to the DST reported satisfaction with MyPrEP. CONCLUSIONS: Among AGYW attending a South African PHC clinic, PrEP uptake was >90% with two-fold higher PrEP persistence at 1 month in those randomized to use the MyPrEP DST. Given the need for strategies to support PrEP implementation and improve low PrEP persistence among African AGYW, a PrEP DST warrants further evaluation.

Association of sexual relationship power with PrEP persistence and other sexual health outcomes among adolescent and young women in Kenya and South Africa.

Introduction: Gendered power inequalities impact adolescent girls' and young women's (AGYW) sexual and reproductive health (SRH) outcomes. We investigated the influence of sexual relationship power on AGYW's SRH outcomes, including HIV pre-exposure prophylaxis (PrEP) persistence. Methods: The POWER study in Kisumu, Kenya, and Cape Town and Johannesburg, South Africa provided PrEP to 2,550 AGYW (aged 16-25). AGYW's perceived power in their primary sexual relationship was measured among the first 596 participants enrolled using the Sexual Relationship Power Scale's (SRPS) relationship control sub-scale. Multivariable regression was used to test for (1) key sociodemographic and relationship characteristics associated with relationship power; and (2) the association of relationship power with SRH outcomes including PrEP persistence. Results: In this cohort, the mean SRPS score was 2.56 (0.49), 542 (90.9%) initiated PrEP; 192 (35.4%) persisted with PrEP at 1 month of which 46 (24.0% of 192) persisted at 6 months. SRPS were significantly lower among AGYW who cohabited with their sex partner (-0.14, 95% CI: -0.24 to -0.04, p = 0.01), or had ≥1 sex partner (-0.10, 95% CI: -0.19 to -0.00, p = 0.05). AGYW with lower SRPS were more likely to not know their partner's HIV status (aOR 2.05, 95% CI: 1.27 to 3.33, p < 0.01), but SRPS was not associated with PrEP persistence, STI infection, condom, or hormonal contraception use. Discussion: AGYW's reasons for initiating PrEP and reasons for continuously using PrEP may be different. While low relationship power was associated with perceived HIV vulnerability, AGYW's PrEP persistence may be influenced by more than relationship power.

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.

Impact of one and two human papillomavirus (HPV) vaccine doses on community-level HPV prevalence in South African adolescent girls: study protocol and rationale for a pragmatic before-after design.

INTRODUCTION: Vaccines against human papillomavirus (HPV) are the key to controlling cervical cancer in low/middle-income countries (LMICs) where incidence is highest, but there have been limited data from these settings on programme impact on HPV prevalence, and none in a population with endemic HIV infection. Furthermore, for many LMICs, the currently recommended two-dose schedule is difficult to deliver at scale, so there is mounting interest in a single-dose schedule. METHODS AND ANALYSIS: The Human Papillomavirus One and Two-Dose Population Effectiveness Study is a hybrid impact evaluation of the national South African HPV vaccination programme, which has targeted grade 4 girls aged at least 9 years in public schools with two doses of vaccine since 2014, and a single-dose vaccine 'catch-up' programme delivered in one district in 2019. Impacts of both schedules on the prevalence of type-specific HPV infection will be measured using repeat cross-sectional surveys in adolescent girls and young women aged 17-18 years recruited at primary healthcare clinics in the four provinces. A baseline survey in 2019 measured HPV prevalence in the cohort who were ineligible for vaccination because they were already above the target age or grade under either the national programme or the single-dose programme in the selected district. HPV prevalence surveys are repeated in 2021 in the selected district, and in 2023 in all four provinces. We will calculate prevalence ratios to compare the prevalence of HPV types 16 and 18 in the single-dose (2021) and two-dose (2023) cohorts, with the vaccine-ineligible (2019) cohort. ETHICS AND DISSEMINATION: The project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC #181005), and the University of New South Wales HREC (#181-005). Findings will be disseminated through peer-reviewed journals, scientific meetings, reports and community forums.

Adolescent girls and young women's PrEP-user journey during an implementation science study in South Africa and Kenya.

Successful scale-up of PrEP for HIV prevention in African adolescent girls and young women (AGYW) requires integration of PrEP into young women's everyday lives. We conducted interviews and focus group discussions with 137 AGYW PrEP users aged 16-25 from South Africa and Kenya. Individual and relational enablers and disablers were explored at key moments during their PrEP-user journey from awareness, initiation and early use through persistence, including PrEP pauses, restarts, and discontinuation. PrEP uptake was facilitated when offered as part of an integrated sexual reproductive health service, but hampered by low awareness, stigma and misconceptions about PrEP in the community. Daily pill-taking was challenging for AGYW due to individual, relational and structural factors and PrEP interruptions (intended or unintended) were described as part of AGYW's PrEP-user journey. Disclosure, social support, adolescent-friendly health counseling, and convenient access to PrEP were reported as key enablers for PrEP persistence.

Health Care Providers as Agents of Change: Integrating PrEP With Other Sexual and Reproductive Health Services for Adolescent Girls and Young Women.

Background: Successful integration of pre-exposure prophylaxis (PrEP) with existing reproductive health services will require iterative learning and adaptation. The interaction between the problem-solving required to implement new interventions and health worker motivation has been well-described in the public health literature. This study describes structural and motivational challenges faced by health care providers delivering PrEP to adolescent girls and young women (AGYW) alongside other SRH services, and the strategies used to overcome them. Methods: We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) with HCWs from two demonstration projects delivering PrEP to AGYW alongside other SRH services. The Prevention Options for the Women Evaluation Research (POWER) is an open label PrEP study with a focus on learning about PrEP delivery in Kenyan and South African family planning, youth mobile services, and public clinics at six facilities. PrIYA focused on PrEP delivery to AGYW via maternal and child health (MCH) and family planning (FP) clinics in Kenya across 37 facilities. IDIs and FGDs were transcribed verbatim and analyzed using a combination of inductive and deductive methods. Results: We conducted IDIs with 36 participants and 8 FGDs with 50 participants. HCW described a dynamic process of operationalizing PrEP delivery to better respond to patient needs, including modifying patient flow, pill packaging, and counseling. HCWs believed the biggest challenge to sustained integration and scaling of PrEP for AGYW would be lack of health care worker motivation, primarily due to a misalignment of personal and professional values and expectations. HCWs frequently described concerns of PrEP provision being seen as condoning or promoting unprotected sex among young unmarried, sexually active women. Persuasive techniques used to overcome these reservations included emphasizing the social realities of HIV risk, health care worker professional identities, and vocational commitments to keeping young women healthy. Conclusion: Sustained scale-up of PrEP will require HCWs to value and prioritize its incorporation into daily practice. As with the provision of other SRH services, HCWs may have moral reservations about providing PrEP to AGYW. Strategies that strengthen alignment of HCW personal values with professional goals will be important for strengthening motivation to overcome delivery challenges.

Cost-Effectiveness of HIV Pre-exposure Prophylaxis Among Heterosexual Men in South Africa: A Cost-Utility Modeling Analysis.

INTRODUCTION: Heterosexual men are not considered a key population in the HIV response and are mostly absent from pre-exposure prophylaxis (PrEP) studies to date. Yet, South African men face considerable HIV risk. We estimate the incremental cost-effectiveness of providing oral PrEP, injectable PrEP, or a combination of both to heterosexual South African men to assess whether providing PrEP would efficiently use resources. METHODS: Epidemiological and costing models estimated the one-year costs and outcomes associated with PrEP use in 3 scenarios. PrEP uptake was estimated for younger (aged 18-24) and older (aged 25-49) men using a discrete choice experiment. Scenarios were compared with a baseline scenario of male condom use, while a health system perspective was used to estimate discounted lifetime costs averted per HIV infection. PrEP benefit was estimated in disability-adjusted life years (DALYs) averted. Uncertainty around the estimated incremental cost-effectiveness ratios (ICERs) was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: No PrEP intervention scenarios were cost-effective for both age groups at a willingness-to-pay threshold of $1175/DALY averted. The lowest ICER ($2873/DALY averted) was for the provision of oral PrEP to older men, although probability of cost-effectiveness was just 0.26%. Results found that ICERs were sensitive to HIV incidence and antiretroviral coverage. CONCLUSIONS: This study estimates that providing PrEP to heterosexual South African men is not cost-effective at current cost-effectiveness thresholds. Given the ICERs' sensitivity to several variables, alongside the heterogeneity of HIV infection among South African men, PrEP may be cost-effective for older men with high incidence and other subgroups based on locality and race. We recommend further investigation to better identify and target these groups.