Sexual Relationship Types, Partner HIV Self-Testing, and Pre-Exposure Prophylaxis Among South African Adolescent Girls and Young Women: A Latent Class Analysis.

BACKGROUND: Sexual relationships among adolescent girls and young women (AGYW) are influenced by social, economic, and gender dynamics. Understanding AGYW's different relationship types and their implications for HIV risk is important for development of tailored interventions. We sought to identify relationship typologies among AGYW and their impact on uptake of HIV prevention interventions. METHODS: From May 2018 to February 2019, 2200 HIV-negative AGYW (ages 16-24) in Johannesburg, South Africa, participated in an HIV prevention intervention involving distribution of HIV self-test kits to their male partners. AGYW were also offered pre-exposure prophylaxis. At baseline, AGYW completed a questionnaire, and outcomes were assessed for 3 months. We used latent class analysis to identify relationship types and mixture modeling to estimate the impact of relationship type on engagement in prevention interventions. RESULTS: We identified 3 relationship types: "stable, empowered relationships with older partners" (class 1, n = 973); "shorter, empowered relationships with peer partners" (class 2, n = 1067); and "shorter relationships with risky partners" (class 3, n = 160). Compared with AGYW in class 1 relationships, AGYW in class 2 and 3 relationships were less likely to complete partner testing alongside HIV results sharing (class 2 adjusted risk ratio: 0.89, 95% confidence interval: 0.85 to 0.95; class 3 adjusted risk ratio: 0.84, 95% confidence interval: 0.73 to 0.94). Pre-exposure prophylaxis uptake was highest in class 3 (11.2%) compared with class 2 (3.8%) and class 1 (1.0%; P < 0.001). CONCLUSIONS: Relationship type impacts uptake of HIV prevention interventions among South African youth. Intervention effectiveness could be optimized by using tailored approaches to HIV risk mitigation among AGYW.

Qualitative characterizations of relationships among South African adolescent girls and young women and male partners: implications for engagement across HIV self-testing and pre-exposure prophylaxis prevention cascades.

INTRODUCTION: Adolescent girls and young women (AGYW) in sub-Saharan Africa have emerged as a priority population in need of HIV prevention interventions. Secondary distribution of home-based HIV self-test kits by AGYW to male partners (MP) is a novel prevention strategy that complements pre-exposure prophylaxis (PrEP), a female-controlled prevention intervention. The objective of this analysis was to qualitatively operationalize two HIV prevention cascades through the lens of relationship dynamics for secondary distribution of HIV self-tests to MP and PrEP for AGYW. METHODS: From April 2018 to December 2018, 2200 HIV-negative AGYW aged 16-24 years were enrolled into an HIV prevention intervention which involved secondary distribution of self-tests to MP and PrEP for AGYW; of these women, 91 participants or MP were sampled for in-depth interviews based on their degree of completion of the two HIV prevention cascades. A grounded theory approach was used to characterize participants' relationship profiles, which were mapped to participants' engagement with the interventions. RESULTS: In cases where AGYW had a MP with multiple partners, AGYW perceived both interventions as inviting distrust into the relationship and insinuating non-monogamy. Many chose not to accept either intervention, while others accepted and attempted to deliver the self-test kit but received a negative reaction from their MP. In the few cases where AGYW held multiple partnerships, both interventions were viewed as mechanisms for protecting one's health, and these AGYW exhibited confidence in accepting and delivering the self-test kits and initiating PrEP. Women who indicated intimate partner violence experiences chose not to accept either intervention because they feared it would elicit a violent reaction from their MP. For AGYW in relationships described as committed and emotionally open, self-test kit delivery was completed with ease, but PrEP was viewed as unnecessary. MP experience with the cascade corroborated AGYW perspectives and demonstrated how men can perceive female-initiated HIV prevention options as beneficial for AGYW and a threat to MP masculinity. CONCLUSIONS: Screening to identify AGYW relationship dynamics can support tailoring prevention services to relationship-driven barriers and facilitators. HIV prevention counseling for AGYW should address relationship goals or partner's influence, and engage with MP around female-controlled prevention interventions.

Perceptions of Community and Clinic-Based Adherence Clubs for Patients Stable on Antiretroviral Treatment: A Mixed Methods Study.

Adherence clubs for patients stable on antiretroviral treatment (ART) offer decongestion of clinics and task-shifting, improved adherence and retention in care. Findings on patient acceptability by club location (in the clinic vs. the community) are limited. This was a mixed-methods study set within a randomized controlled trial of community versus clinic-based adherence clubs for retention in care at Witkoppen Health and Welfare Centre in Johannesburg, South Africa. Participants were surveyed on preferences for adherence club-based care (e.g. location, convenience). We conducted in-depth interviews (IDIs) with 36 participants, and surveyed 568 participants: 49% in community-based clubs and 51% in clinic-based clubs. Participants in both arms favorably rated adherence clubs. Almost all (95%) in clinic-based clubs would recommend them to a friend, while fewer (88% in community-based club participants would do so (p = 0.004). Participants found clubs promoted social support, and were convenient and time-saving, though concerns around stigma and access to other health care were noted within community-based clubs. Adherence clubs are a highly acceptable form of differentiated care for stable ART patients. These data indicate that clinic-based clubs may be preferred above community-based clubs, potentially for reasons of stigma and access to additional health care services.

HIV incidence, pregnancy, and implementation outcomes from the Sakh'umndeni safer conception project in South Africa: a prospective cohort study.

BACKGROUND: Safer conception strategies empower individuals trying to conceive to minimise HIV transmission risk to partners and potential children; however, effectiveness data are scarce. We aimed to assess adoption of safer conception methods and HIV and pregnancy outcomes from Sakh'umndeni, a novel safer conception service in South Africa. METHODS: In this prospective cohort study, the Sakh'umndeni clinical cohort at Witkoppen Cinic in Johannesburg (South Africa) enrolled adults aged at least 18 years who were trying to conceive and in relationships with an HIV-positive partner. Couples who were pregnant at enrolment or had been previously diagnosed as infertile were excluded. Participants received safer conception care by a nurse, including antiretroviral therapy (ART) for HIV-positive partners, pre-exposure prophylaxis (PrEP) for HIV-negative partners, counselling around timed condomless sex, or syringes for self-insemination. Primary outcomes were pregnancy incidence and HIV transmission to partners and infants. We estimated time to first pregnancy using Kaplan-Meier curves; pregnancy and HIV incidence were estimated as events per person-years of risk. FINDINGS: Between July 16, 2013, and April 5, 2017, 526 individuals (334 women and 192 men) from 334 partnerships enrolled. 162 (48%) of 334 couples were serodifferent, 149 (45%) were HIV-positive seroconcordant, and 23 (7%) were an HIV-positive woman and an unknown status male partner. At enrolment, 176 (61%) of 287 HIV-positive women and 60 (46%) of 131 HIV-positive men were virally suppressed (<50 copies per mL). Among the safer conception strategies, ART was initiated by 73 (91%) of 80 HIV-positive participants not on ART and PrEP was initiated by 28 (28%) of 101 HIV-negative participants. 2719 follow-up visits were completed, and 99 pregnancies were observed in 89 women. Pregnancy incidence was 41·2 per 100 person-years (95% CI 33·4-50·7); 25 (28%) of 89 pregnancies with a known outcome were miscarried or terminated because of risk to the mother. Pregnancy incidence was 79·0 per 100 person-years (95% CI 49·8-125·4) among HIV-negative women and 36·7 per 100 person-years (29·1-46·3) among HIV-positive women. At the time of pregnancy, viral suppression among women was high (68 [87%] of 78 women had viral loads of <50 copies per mL and 77 [99%] had viral loads of <1000 copies per mL). No horizontal or vertical HIV transmission events were observed. INTERPRETATION: Safer conception strategies empowered couples to safely conceive. Pregnancy incidence among service users was high. Integration of safer conception counselling could promote HIV prevention and linkage to care. FUNDING: US Agency for International Development; UJMT Consortium/Fogarty International Center, US National Institutes of Health (NIH); and Johns Hopkins University Center for AIDS Research (NIH).

Integrating safer conception services into primary care: providers' perspectives.

BACKGROUND: In 2012, South Africa adopted the Contraception and Fertility Planning guidelines to incorporate safer conception services into care for HIV-affected couples trying to conceive. These guidelines lacked clear implementation and training recommendations. The objective of this study was to investigate factors influencing integration of safer conception services in a clinical setting. METHODS: Twenty in-depth interviews were conducted between October-November 2017 with providers and staff at Witkoppen Clinic in Johannesburg, where the Sakh'umndeni safer conception demonstration project had enrolled patients from July 2013-July 2017. Semi-structured interview guides engaged providers on their perspectives following the Sakh'umndeni project and possible integration plans to inform the translation of the stand-alone Sakh'umndeni services into a routine service. A grounded theory approach was used to code interviews and an adaptation of the Atun et al. (2010) 'Integration of Targeted Interventions into Health Systems' conceptual framework was applied as an analysis tool. RESULTS: Five themes emerged: (1) The need for safer conception training; (2) The importance of messaging and demand generation; (3) A spectrum of views around the extent of integration of safer conception services; (4) Limitations of family planning services as an integration focal point; and (5) Benefits and challenges of a "couples-based" intervention. In-depth interviews suggested that counselors, as the first point of contact, should inform patients about safer conceptions services, followed by targeted reinforcement of safer conception messaging by all clinicians, and referral to more intensively trained safer conception providers. CONCLUSION: A safer conception counseling guide would facilitate consultations. While many providers felt that the services belonged in family planning, lack of HIV management skills, men and women trying to conceive within family planning may pose barriers.

The impact of community- versus clinic-based adherence clubs on loss from care and viral suppression for antiretroviral therapy patients: Findings from a pragmatic randomized controlled trial in South Africa.

BACKGROUND: Adherence clubs, where groups of 25-30 patients who are virally suppressed on antiretroviral therapy (ART) meet for counseling and medication pickup, represent an innovative model to retain patients in care and facilitate task-shifting. This intervention replaces traditional clinical care encounters with a 1-hour group session every 2-3 months, and can be organized at a clinic or a community venue. We performed a pragmatic randomized controlled trial to compare loss from club-based care between community- and clinic-based adherence clubs. METHODS AND FINDINGS: Patients on ART with undetectable viral load at Witkoppen Health and Welfare Centre in Johannesburg, South Africa, were randomized 1:1 to a clinic- or community-based adherence club. Clubs were held every other month. All participants received annual viral load monitoring and medical exam at the clinic. Participants were referred back to clinic-based standard care if they missed a club visit and did not pick up ART medications within 5 days, had 2 consecutive late ART medication pickups, developed a disqualifying (excluding) comorbidity, or had viral rebound. From February 12, 2014, to May 31, 2015, we randomized 775 eligible adults into 12 pairs of clubs-376 (49%) into clinic-based clubs and 399 (51%) into community-based clubs. Characteristics were similar by arm: 65% female, median age 38 years, and median CD4 count 506 cells/mm3. Overall, 47% (95% CI 44%-51%) experienced the primary outcome of loss from club-based care. Among community-based club participants, the cumulative proportion lost from club-based care was 52% (95% CI 47%-57%), compared to 43% (95% CI 38%-48%, p = 0.002) among clinic-based club participants. The risk of loss to club-based care was higher among participants assigned to community-based clubs than among those assigned to clinic-based clubs (adjusted hazard ratio 1.38, 95% CI 1.02-1.87, p = 0.032), after accounting for sex, age, nationality, time on ART, baseline CD4 count, and employment status. Among those who were lost from club-based care (n = 367), the most common reason was missing a club visit and the associated ART medication pickup entirely (54%, 95% CI 49%-59%), and was similar by arm (p = 0.086). Development of an excluding comorbidity occurred in 3% overall of those lost from club-based care, and was not different by arm (p = 0.816); no deaths occurred in either arm during club-based care. Viral rebound occurred in 13% of those lost from community club-based care and 21% of those lost from clinic-based care (p = 0.051). In post hoc secondary analysis, among those referred to standard care, 72% (95% CI 68%-77%) reengaged in clinic-based care within 90 days of their club-based care discontinuation date. The main limitations of the trial are the lack of a comparison group receiving routine clinic-based standard care and the potential limited generalizability due to the single-clinic setting. CONCLUSIONS: These findings demonstrate that overall loss from an adherence club intervention was high in this setting and that, importantly, it was worse in community-based adherence clubs compared to those based at the clinic. We urge caution in assuming that the effectiveness of clinic-based interventions will carry over to community settings, without a better understanding of patient-level factors associated with successful retention in care. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR201602001460157).

Subfertility among HIV-affected couples in a safer conception cohort in South Africa.

BACKGROUND: Subfertility among couples affected by HIV has an impact on the well-being of couples who desire to have children and may prolong HIV exposure. Subfertility in the antiretroviral therapy era and its determinants have not yet been well characterized. OBJECTIVE: The objective of the study was to investigate the burden and determinants of subfertility among HIV-affected couples seeking safer conception services in South Africa. STUDY DESIGN: Nonpregnant women and male partners in HIV seroconcordant or HIV discordant relationships desiring a child were enrolled in the Sakh'umndeni safer conception cohort at Witkoppen Clinic in Johannesburg between July 2013 and April 2017. Clients were followed up prospectively through pregnancy (if they conceived) or until 6 months of attempted conception, after which they were referred for infertility services. Subfertility was defined as not having conceived within 6 months of attempted conception. Robust Poisson regression was used to assess the association between baseline characteristics and subfertility outcomes; inverse probability weighting was used to account for missing data from women lost to safer conception care before 6 months of attempted conception. RESULTS: Among 334 couples enrolled, 65% experienced subfertility (inverse probability weighting weighted, 95% confidence interval, 0.59-0.73), of which 33% were primary subfertility and 67% secondary subfertility. Compared with HIV-negative women, HIV-positive women not on antiretroviral therapy had a 2-fold increased risk of subfertility (weighted and adjusted risk ratio, 2.00; 95% confidence interval, 1.19-3.34). Infertility risk was attenuated in women on antiretroviral therapy but remained elevated, even after ≥2 years on antiretroviral therapy (weighted and adjusted risk ratio, 1.63; 95% confidence interval, 0.98-2.69). Other factors associated with subfertility were female age (weighted and adjusted risk ratio, 1.03, 95% confidence interval, 1.01-1.05 per year), male HIV-positive status (weighted and adjusted risk ratio, 1.31; 95% confidence interval, 1.02-1.68), male smoking (weighted and adjusted risk ratio, 1.29; 95% confidence interval, 1.05-1.60), and trying to conceive for ≥1 year (weighted and adjusted risk ratio, 1.38; 95% confidence interval, 1.13-1.68). CONCLUSION: Two in 3 HIV-affected couples experienced subfertility. HIV-positive women were at increased risk of subfertility, even when on antiretroviral therapy. Both male and female HIV status were associated with subfertility. Subfertility is an underrecognized reproductive health problem in resource-limited settings and may contribute to prolonged HIV exposure and transmission within couples. Low-cost approaches for screening and treating subfertility in this population are needed.

Mental health in South African adolescents living with HIV.

We examined the prevalence of mental health conditions, social support, and associated factors among adolescents living with HIV. We conducted a cross-sectional analysis with adolescents (ages 9-19) attending a primary care clinic in Johannesburg, South Africa. We analyzed the results of four self-report tools: Children's Depression Inventory-Short, Revised Manifest Anxiety Scale, Child Post-Traumatic Stress Disorder (PTSD) Checklist, and a modified version of the Medical Outcomes Study Social Support Scale. We used robust Poisson regression to quantify the association between social support and mental health. Among 278 adolescents, the majority were perinatally infected with HIV (92%), and had at least one deceased parent (59%). Depression symptom threshold scores were found among 8% of adolescents, and 7% screened positive for symptoms of anxiety. Few (1%) met the criteria for PTSD. Overall, 12% of adolescents screened positive for symptoms of depression, anxiety or PTSD. Older adolescents reported less social support than younger adolescents. Adolescents were less likely to have mental health symptoms if they had higher measures of social support (adjusted Prevalence Ratio 0.38, 95% CI 0.20-0.73). Attention should be paid to social support for adolescents living with HIV as this may play an important role in their mental health.