Acceptability of the Dapivirine Vaginal Ring and Oral Truvada Among African Users in Late-Stage of Pregnancy.

The Microbicide Trials Network 042 study (MTN-042/DELIVER) is a two-arm, randomized, open-label Phase 3b trial that is evaluating the safety, adherence, and acceptability of the monthly ring and daily oral PrEP among HIV-uninfected pregnant people in four African countries. This analysis focuses on acceptability data captured qualitatively from a subset (n = 48) of the 150 people in the first cohort of the trial who were enrolled in late-stage pregnancy at 36 to 38 weeks gestational age and followed until after delivery. Single IDIs were conducted by trained interviewers at each clinic site using a semi-structured guide. Data excerpts of key codes pertaining to acceptability, pregnancy, and maternal health were summarized, reviewed and interpreted by multinational analyst teams. Although the product use period was relatively short, the data suggested several acceptability findings that may directly translate to longer durations of product use in pregnancy. The first was the overarching maternal sentiment that being able to protect both oneself and their baby was highly valued. The second was the importance of counseling support from providers not only because participants used methods that might generate side effects, but because pregnancy itself is a period with its own set of side effects. The third was that, similar to non-pregnant participants in other trials, here study products were generally liked and described as easy to use. Concerns about ring and oral PrEP use could be addressed with provider counseling and support and should form an essential component rollout among pregnant people.

Developmental Trajectories of Transactional Sex and Age-Disparate Relationships During Adolescence: An HPTN 068 Analysis.

Transactional sex and sexual relationships with older partners increase HIV risk in adolescent girls and young women (AGYW), yet little is known about how these behaviors co-evolve over time. We characterize temporal patterns of transactional sex and age-disparate relationships among AGYW in South Africa. Longitudinal data are from a randomized controlled trial (HPTN 068) of school-aged, HIV-negative, AGYW who attended ≥ 3 study visits. We used group-based trajectory modeling to identify trajectories of transactional sex and age-disparate relationships (partner ≥ 5 years older) in the last year and assessed the interrelationship (conditional probability) between both trajectories. At baseline, median age was 14 years, 14.5% of girls were sexually active, and transactional sex (2.1%) and age-disparate relationships were uncommon (2.7%). We identified two trajectories for transactional sex ("low" [81.9%] and "increasing" [18.1%]) and two for age-disparate relationships ("low" [91.7%] and "increasing" [8.3%]). In a separate joint trajectory analysis, nearly a third (28%) had increasing trajectories for both transactional sex and age-disparate relationships, but most (53%) had a low trajectory of both outcomes. Baseline reporting of early sexual debut, depression, and inequitable gender norms were highest in the increasing transactional sex group. Prior pregnancy, early sexual debut, and IPV were highest among those with increasing age-disparate relationships. AGYW who engage in transactional sex or age-disparate partnerships in early adolescence are more likely to experience sustained engagement in both behaviors as they transition to adulthood, increasing HIV risk. Engaging girls early may maximize effectiveness of behavioral and biomedical HIV prevention efforts.

Depression Among Pregnant and Breastfeeding Persons Participating in Two Randomized Trials of the Dapivirine Vaginal Ring and Oral Pre-Exposure Prophylaxis (PrEP) in Malawi, South Africa, Uganda, and Zimbabwe.

Depression is associated with lower adherence to oral pre-exposure prophylaxis (PrEP) to prevent HIV, but data are not currently available on how depression may affect use of other HIV prevention methods including the dapivirine vaginal ring (DVR). We conducted a mixed methods study using data from the Microbicide Trials Network (MTN) 042/DELIVER (n = 558) and MTN-043/B-PROTECTED (n = 197) studies to describe the prevalence of depressive symptoms and explore how depressive symptoms may have influenced attitudes about use of the monthly DVR and once-daily oral PrEP tablet among pregnant and breastfeeding persons, respectively, in Malawi, South Africa, Uganda, and Zimbabwe. Eleven participants had high Edinburgh Postnatal Depression scores ≥ 10 in MTN-042/DELIVER (2%) and four participants (2%) in MTN-043/B-PROTECTED. In interviews with 9 participants who had high scores (6 DVR, 3 oral PrEP), those with depressive symptoms described overlapping stressors which were magnified by job loss and economic instability during the COVID-19 pandemic, and by experiences of pregnancy/postpartum. These participants experienced a lack of support from partners or family members, and conflict with partners related to trust, and infidelity. While we did not find evidence of a change in product adherence, there was a strong sense of commitment and motivation to use the study products for protection from HIV for participants themselves and their baby. Although lack of social support is usually an obstacle to adherence, in this study, the participants' lives and relationships seemed to have reinforced the need for HIV prevention and motivated women to protect themselves and their babies from HIV.

Acceptability of the Dapivirine Vaginal Ring and Daily Oral Pre-exposure Prophylaxis (PrEP) during Pregnancy in Malawi, South Africa, Uganda, and Zimbabwe.

Pregnant and lactating persons in sub-Saharan Africa face a heightened risk of HIV acquisition, due to biological and behavioral factors, combined with limited access to prevention and treatment services. Oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring are promising tools for HIV prevention, and the ring's recent approval in multiple African countries represents a significant advancement in expanding access to HIV prevention. In a nested qualitative study within the MTN-042 trial, we explored the acceptability of study products among pregnant persons in the second and early third trimesters. Interviews were conducted privately, using a semi-structured guide with 77 participants, in participants' preferred language. Topics explored included product acceptability (using the theoretical framework of acceptability), user experience, satisfaction, disclosure, community attitudes, and sexual activity during pregnancy. Interview transcripts were analyzed using Dedoose software. We observed positive attitudes among participants towards the study products, which they found generally user-friendly, despite the added complexities of using them during pregnancy. Participants recognized that consistent and correct use would provide protection for both them and their unborn children. Although initial concerns existed, most of these worries dissipated over time, with study staff support and increased product use experience. These findings emphasize the importance of continued surveillance, support, and education to ensure the successful rollout of new HIV prevention measures during pregnancy.

Acceptability of the dapivirine vaginal ring for HIV-1 prevention among women reporting engagement in transactional sex.

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015; n = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use. We used Poisson regression models with robust standard errors to compare risk of acceptability challenges by baseline history of transactional sex. At product discontinuation, women exchanging sex found the ring comfortable (90%), easy to insert (92%) and nearly all (96%) were likely to use the ring in the future. Women who had exchanged sex were more likely to report feeling the ring during sex (ARR 1.43, 95% CI: 1.09, 1.89; p = 0.01) and slightly more likely to mind wearing the ring during menses (ARR 1.22, 95% CI: 1.01, 1,46; p = 0.04) and during sex (ARR 1.22, 95% CI: 1.02, 1.45; p = 0.03). Messaging and counseling should include enhanced support for use during sex and menses to support optimal use.

Acceptability and Use of the Dapivirine Vaginal Ring and Daily Oral Pre-exposure Prophylaxis (PrEP) During Breastfeeding in South Africa, Malawi, Zimbabwe, and Uganda.

This study examines qualitative acceptability of the dapivirine vaginal ring (DVR) and oral daily pre-exposure prophylaxis (PrEP) among breastfeeding persons participating in Microbicide Trials Network 043/B-PROTECTED, a phase 3B safety and drug detectability study of DVR and oral PrEP in breastfeeding. A subsample of 52 participants were purposively sampled to participate in an in-depth interview (IDI). Breastfeeding participants found both study products to be acceptable, and easy to use. A common motivation for product use was to protect the baby from HIV, although participants' understanding of how the study drug would work to protect their babies was often unclear. While most participants did not report experiencing side effects, fears about side effects were common as both initial worries about how the study products would affect their health and the health of their baby, and increased anxiety that health issues experienced by them, or their baby were from the products.

Couples' decision making regarding the use of multipurpose prevention technology (MPT) for pregnancy and HIV prevention.

We conducted a secondary analysis of discrete choice experiment (DCE) data from 395 couples enrolled in the Microbicide Trials Network (MTN)-045/CUPID study in Uganda and Zimbabwe to understand couple decision making around choice of multipurpose prevention technologies (MPTs) to prevent both HIV and pregnancy. Members of couples completed the same DCE, first separately then jointly, choosing between two hypothetical MPTs in a series of nine questions. Most couples either had similar preferences at the outset or had equal decision-making around MPTs (62%). Couples with male influence (17%) were more likely to use contraceptive pills with a male partner's knowledge and couples with female influence (21%) were less likely to have shared decision making about family planning. Males influenced discussion around MPT duration, side effects, menstrual changes, and how the vagina feels during sex. Decision making was relatively shared, though decisions around certain attributes were more likely to be dominated by male partners.

Using Participatory Methods to Assess PrEP Interest and Uptake Among Young People Living in the Southeastern US: A Mixed Methods Assessment.

Adolescents and young adults (AYA; 13-24 years-old) comprise 22% of new HIV infections in the United States (US), most of whom live in the South. We used the situated-Information, Motivation, Behavioral skills (sIMB) model to identify priorities for intervention on multi-level factors that influence HIV preventive care among Black AYA in Durham, North Carolina. We conducted two participatory workshops (ages 13-17, N = 6; ages 18-24, N = 7) to engage youth about how to discuss HIV. We also assessed sIMB constructs from a separate quantitative sample of youth to contextualize the workshop findings (N = 80). HIV knowledge was low overall, but lower among younger Black AYA, suggesting a need for comprehensive sexual education. Trusted adults provided sexual health information, motivation for health maintenance, and behavioral skills support. HIV prevention interventions should provide comprehensive sexual health education to Black AYA, be age-specific, and include social supporters like parents, teachers, and community members.

Couples' Preferences for "2 in 1" Multipurpose Prevention Technologies to Prevent Both HIV and Pregnancy: Results of a Discrete Choice Experiment in Uganda and Zimbabwe.

End-user input early in biomedical product development may optimize design to support high uptake and adherence. We interviewed 400 couples (800 total participants) in Uganda and Zimbabwe to assess their preferences for multipurpose prevention technologies (MPTs) for HIV and pregnancy prevention. Using a discrete choice experiment, couples made a series of choices between hypothetical MPTs, including oral tablets and vaginal rings, inserts, and films and completed an interviewer-administered questionnaire assessing sociodemographic and behavioral measures. Most couples preferred presented MPTs over male condoms. Couples' MPT choices in both countries were influenced most by the combination of product form and dosing frequency, with monthly dosing preferred over daily. Analysis highlighted differences by country as to which side effects were most important: Ugandan couples placed greater importance on effects on the vaginal environment during sex, whereas Zimbabwean couples placed more importance on changes to menstruation and other side effects (headache, cramps). Couples' preferences signaled an openness to new product forms and more frequent dosing if preferred characteristics of other attributes were achieved.

Social environment risk factors for violence, family context, and trajectories of social-emotional functioning among Latinx adolescents.

INTRODUCTION: High social-emotional functioning, including emotion regulation and nonviolent conflict resolution, constitute developmental competencies of adolescence that promote health and well-being. We used prospective longitudinal data from a predominantly Latinx population to understand how family context and social environment risk factors for violence related to patterns of social-emotional functioning during the transition between middle school and high school. METHODS: We prospectively interviewed 599 8th graders every 6 months for 2 years. We used trajectory models to explore longitudinal patterns of emotion regulation and nonviolent problem solving and multinomial regression to distinguish how these groups were associated with family context, partner and peer gang involvement, and neighborhood social disorder. RESULTS: Youth reporting lower neighborhood disorder in 8th grade were more likely to be in the high emotion regulation trajectory group. Youth without exposure to gangs through peers and partners in 8th grade were more likely to be in the high nonviolent problem-solving skills trajectory group. Family cohesion was associated with being in the high trajectory groups for both emotional regulation and problem-solving skills. CONCLUSION: Emotion regulation and nonviolent problem-solving skills had different associations with the social environment risk factors for violence examined, indicating that mechanisms of influence and strategies for intervention may vary. The association between problem-solving skills and exposure to gangs through peers and partners shows that social norms may be important targets of change. Additionally, interventions with parents that build family cohesion during adolescence may buffer environmental exposures that shape adolescents' ability to practice protective social-emotional behaviors.

Modeling Combination Interventions to Prevent Human Immunodeficiency Virus in Adolescent Girls and Young Women in South Africa (HIV Prevention Trials Network 068).

BACKGROUND: Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV. METHODS: We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors. RESULTS: Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%). CONCLUSIONS: To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.

Cash transfers for HIV prevention: A systematic review.

BACKGROUND: Given the success of cash programs in improving health outcomes and addressing upstream drivers of HIV risk such as poverty and education, there has been an increasing interest in their potential to improve HIV prevention and care outcomes. Recent reviews have documented the impacts of structural interventions on HIV prevention, but evidence about the effects of cash transfer programs on HIV prevention has not been systematically reviewed for several years. METHODS AND FINDINGS: We did a systematic review of published and unpublished literature to update and summarize the evidence around cash programs for HIV prevention from January 2000 to December 17, 2020. We included studies with either a cash transfer intervention, savings program, or program to reduce school costs. Included studies measured the program's impact on HIV infection, other sexually transmitted infections (STIs), or sexual behaviors. We screened 1,565 studies and examined 78 in full-text review to identify a total of 45 peer-reviewed publications and reports from 27 different interventions or populations. We did not do a meta-analysis given the range of outcomes and types of cash transfer interventions assessed. Most studies were conducted in sub-Saharan Africa (N = 23; South Africa, Tanzania, Malawi, Lesotho, Kenya, Uganda, Zimbabwe, Zambia, and eSwatini) followed by Mexico (N = 2), the United States (N = 1), and Mongolia (N = 1)). Of the 27 studies, 20 (72%) were randomized trials, 5 (20%) were observational studies, 1 (4%) was a case-control study, and 1 (4%) was quasi-experimental. Most studies did not identify a strong association between the program and sexual behaviors, except sexual debut (10/18 finding an association; 56%). Eight of the 27 studies included HIV biomarkers, but only 3 found a large reduction in HIV incidence or prevalence, and the rest found no statistically significant association. Of the studies that identified a statistically significant association with other STIs (N = 4/8), 2 involved incentives for staying free of the STI, and the other 2 were cash transfer programs for adolescent girls that had conditionalities related to secondary schooling. Study limitations include the small number of studies in key populations and examining interventions to reduce school costs and matched saving programs. CONCLUSIONS: The evidence base for large-scale impacts of cash transfers reducing HIV risk is limited; however, government social protection cash transfer programs and programs that incentivize school attendance among adolescent girls and young women show the greatest promise for HIV prevention.

Trajectories of PrEP Adherence Among Young Women Aged 16 to 25 in Cape Town, South Africa.

Despite demonstrated efficacy for HIV prevention, substantial challenges remain for the successful rollout of oral pre-exposure prophylaxis (PrEP), especially among adolescent girls and young women (AGYW). We characterized trajectories of PrEP adherence among 200 AGYW in South Africa and analyzed data from 22 qualitative interviews and 3 focus group discussions for explanatory purposes. Two adherence trajectory groups were identified: 52% with high early adherence that declined after month three and 48% with low adherence throughout. Adherence in the "consistently low" group was related to social support and logistical concerns, while the decrease in the "high declining" group corresponded to a change in the frequency of study visits from monthly to quarterly. PrEP support should be differentiated for those who need more frequent visits and adherence support initially versus later in PrEP use. Visits every month, when needed, should be considered for AGYW who need sustained support later into use.

Modeling Cash Plus Other Psychosocial and Structural Interventions to Prevent HIV Among Adolescent Girls and Young Women in South Africa (HPTN 068).

Poverty alleviation programs can reduce HIV incidence but may have greater impacts when combined with other psychosocial interventions. We modeled the change in HIV incidence among South African adolescent girls and young women (AGYW) associated with combining a cash transfer (the South African Child Support Grant (CSG)) with other structural and behavioral interventions. We modeled observational data from the HPTN 068 study where 2328 HIV negative AGYW (13-20 years) were followed for 4 years. In a Monte Carlo simulation based on this cohort (N = 10,000), CSG receipt was not independently associated with HIV incidence. Providing the CSG combined with increasing caregiver care and reducing adolescent depression had the largest reduction in HIV incidence with the fewest number of combined interventions (RD - 3.0%; (95% CI - 5.1%, - 0.9%). Combining a monthly grant with interventions to increase caregiver care and reduce adolescent depression could substantially reduce HIV incidence above the provision of cash alone.

The Influence of Perceived Dapivirine Vaginal Ring Effectiveness on Social Disclosure and Ring Adherence.

We analyzed data from 1428 users of the dapivirine vaginal ring, who participated in the MTN-020/ASPIRE phase III trial and subsequent open-label extension MTN-025/HOPE trial, to examine relationships between perceived ring protection, social disclosures, and self-reported ring adherence. In HOPE, 77% perceived the ring to be highly effective, and this view was associated with speaking: (a) to a greater number of people about the study, (b) with other participants, (c) to more people who were in favor of the ring, and (d) to more people whose opinions were valued. Reported adherence was not directly associated with perceived protection but was associated with disclosing to someone who was in favor of the ring. These findings suggest the importance of women's internalized ideas about the protective benefits of the DVR in sharing information about the ring and the importance of social support on adherence.

The effects of a cash transfer intervention on sexual partnerships and HIV in the HPTN 068 study in South Africa.

Evidence on cash transfer interventions for HIV prevention in adolescent girls and young women is unclear and indicates that they may not work uniformly in all settings. Qualitative interviews were conducted with 22 girls and young women post-intervention to determine how a cash transfer study (HPTN 068) in South Africa was perceived to influence sexual behaviours and to explore mechanisms for these changes. Participants described how the intervention motivated them to increase condom use, have fewer partners, end risky relationships and access HIV testing services at local primary health clinics. Changes were attributed to receipt of the cash transfer, in addition to HIV testing and sexual health information. Processes of change included improved communication with partners and increased negotiation power in sexual decision-making. Economic empowerment interventions increase confidence in negotiating behaviours with sexual partners and are complementary to sexual health information and health services that provide young women with a foundation on which to make informed decisions about how to protect themselves.

Characteristics Associated With Human Immunodeficiency Virus Transmission Networks Involving Adolescent Girls and Young Women in Human Immunodeficiency Virus Prevention Trials Network 068 Study.

We combined behavioral survey data from the human immunodeficiency virus (HIV) Prevention Trials Network 068 study with phylogenetic information to determine if cluster membership was associated with characteristics of young women and their partners. Clusters were more likely to involve young women from specific villages and schools, indicating some localized transmission.Supplemental digital content is available in the text.

The Relationship Between Economic Deprivation, Housing Instability and Transactional Sex Among Women in North Carolina (HPTN 064).

Transactional sex is associated with socioeconomic disadvantage and HIV risk but few studies in the United States (US) have examined both individual and area-level predictors of transactional sex or distinguished transactional sex from sex work. We combined data from HIV Prevention Trials Network 064 study and the US Census to estimate prevalence ratios (PR) for the relationship between census-level and individual measures of economic deprivation and housing instability on transactional sex in 417 women in North Carolina. Increased transactional sex was associated with food insecurity (PR 1.86; 95%; CI 1.57, 2.19), housing instability (PR 1.33; 95% CI 1.11, 1.59), substance abuse (PR 1.90; 95% CI 1.64, 2.19) and partner incarceration (PR 1.32; 95% CI 1.09, 1.61). Census-level indicators were not associated with transactional sex, adjusted for individual-level covariates. Interventions should support housing stability and financial opportunities among southern African American women to reduce HIV risk, particularly among women with incarcerated partners.

Timing of Initiation of Antiretroviral Therapy and Risk of Preterm Birth in Studies of HIV-infected Pregnant Women: The Role of Selection Bias.

BACKGROUND: Women who initiate antiretroviral therapy (ART) during pregnancy are reported to have lower risk of preterm birth compared with those who enter pregnancy care already receiving ART. We hypothesize this association can be largely attributed to selection bias. METHODS: We simulated a cohort of 1000 preconceptional, HIV-infected women, where half were randomly allocated to receive immediate ART and half to delay ART until their presentation for pregnancy care. Gestational age at delivery was drawn from population data unrelated to randomization group (i.e., the true effect of delayed ART was null). Outcomes of interest were preterm birth (<37 weeks), very preterm birth (<32 weeks), and extreme preterm birth (<28 weeks). We analyzed outcomes in 2 ways: (1) a prospectively enrolled clinical trial, where all women were considered (the intent-to-treat (ITT) analysis); and (2) an observational study, where women who deliver before initiating ART were excluded (the naïve analysis). We explored the impact of later ART initiation and gestational age measurement error on our findings. RESULTS: Preconception ART initiation was not associated with preterm birth in ITT analyses. Risk ratios (RRs) for the effect of preconception ART initiation were RR = 1.10 (preterm), RR = 1.41 (very preterm), and RR = 5.01 (extreme preterm) in naïve analyses. Selection bias increased in the naïve analysis with advancing gestational age at ART initiation and with introduction of gestational age measurement error. CONCLUSIONS: Analyses of preterm birth that compare a preconception exposure to one that occurs in pregnancy are at risk of selection bias. See video abstract at, http://links.lww.com/EDE/B313.