Associations between intravaginal practices and incidence of sexually transmitted infections and bacterial vaginosis among women enrolled in the dapivirine vaginal ring trial (The Ring Study) in southwestern Uganda: a retrospective secondary analysis.

OBJECTIVES: We assessed associations between intravaginal practices (IVPs) and the incidence of sexually transmitted infections (STIs) and bacterial vaginosis (BV) among women using the dapivirine vaginal ring (DVR) or placebo vaginal ring in southwestern Uganda. METHODS: This was a retrospective secondary analysis of data collected from women at risk of HIV infection recruited into the Ring Study. The latter evaluated the safety and efficacy of the DVR between 2013 and 2016. At baseline, a behavioural questionnaire was administered to obtain information on sexual activity and IVP (exposure) defined as; insertion inside the vagina of any items aimed at cleaning the vagina for any reason before, during or after sex other than practices to manage menses. Each participant self-inserted the DVR/placebo and replaced it every 4 weeks for 2 years. Outcomes were diagnosis of STIs, that is, Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis (TV), HIV and BV. The incidence rate of STI/BV was estimated, overall, by IVP and trial arm in single-event-per-participant and multiple-event-per-participant analyses. RESULTS: Of the 197 women enrolled, 66 (33.5%) were <25 years of age. Overall, 93 (47.2%) practised at least one form of IVP. During the follow-up, 172 (87.3%) women were diagnosed with an STI/BV at least once. The majority had TV (73.6%, n=145). Overall rate of STI/BV was 51.9/100 person-years, 95% CI 44.7 to 60.3 (IVP: yes, 51.0 (40.8-63.8) vs no, 52.6 (43.0-64.4)). IVPs were not statistically significantly associated with rate of individual STIs/BV. Similar results were observed when the analyses were conducted separately for each trial arm. CONCLUSIONS: IVP was not associated with risk of STIs/BV in the Ring Study. TRIAL REGISTRATION NUMBER: NCT01539226.

Peer Pressure and Risk-Taking Behaviors Among Adolescent Girls in a Region Impacted by HIV/AIDS in Southwestern Uganda.

PURPOSE: This paper uses data from a 3-arm Cluster Randomized Control Trial, Suubi4Her (N = 1260; 14-17-year-old school-going girls) to (1) assess the relationship between peer pressure and adolescent risk-taking behaviors; and (2) test the mediating effect of peer pressure on an intervention on adolescent risk-taking behaviors. METHODS: Students in the southwestern region of Uganda were assigned to three study arms: control (n = 16 schools, n = 408 students) receiving usual care comprising of sexual and reproductive health curriculum; and two active treatment arms: Treatment 1 (n = 16 schools, n = 471 students) received everything the control arm received plus a savings led intervention. Treatment 2 (n = 15 schools, n = 381 students) received everything the control and treatment arms received plus a family strengthening intervention. We used multilevel models to assess the relationship between peer pressure and risk-taking behaviors. We ran structural equation models for mediation analysis. RESULTS: Using baseline data, we found that direct peer pressure was significantly associated with substance use risk behaviors, (ß = 0.044, 95% CI = 0.008, 0.079). We also found a statistically significant effect of the intervention on acquiring STIs through the mediating effect of sexual risk-taking significant (ß = -0.025, 95% CI: -0.049, -0.001, p = .045) and total indirect (ß = -0.042, 95% CI: -0.081, -0.002, p = .037) effects. Also, there was a significant mediation effect of the intervention on substance use through peer pressure (ß = -0.030, 95% CI: -0.057, -0.002, p = .033). DISCUSSION: Overall, the study points to the role of peer pressure on adolescent girls' risk-taking behaviors; and a need to address peer pressure at an early stage.

Changes in self-reported risky sexual behaviour indicators among adults receiving regular risk reduction counselling and optional initiation of pre-exposure prophylaxis in an HIV vaccine preparedness study in Masaka, Uganda.

BACKGROUND: HIV risk reduction counselling may reduce risk-taking behaviours. Yet, concerns remain about risk compensation among individuals initiating pre-exposure prophylaxis (PrEP). OBJECTIVE: We assessed changes in risky sexual behaviour indicators among HIV vaccine preparedness study participants who received regular risk reduction counselling and referral for PrEP in Masaka, Uganda. METHODS: Adults (18-39 years) at high risk of HIV infection were enrolled in the study between July 2018 and December 2021. Data were collected on socio-demographic factors (baseline) and self-reported sexual risk behaviours (baseline, six monthly). HIV testing and risk-reduction counselling and referral for PrEP were done quarterly. Participants who had completed at least 1 year of follow-up were included in the analysis. Proportional differences and McNemar chi-square tests were used to assess changes in the prevalence of self-reported risky sexual behaviour indicators between baseline and 1 year. Logistic regression was used to assess the predictors of unchanged/increased HIV risk at 1 year. RESULTS: Three hundred participants [132 (44%) females, 152 (51%) aged ≤24 years] were included in this analysis. Eighty-one (27%) participants initiated PrEP at 1 year. Compared to baseline, there were significant reductions in the prevalence of the following self-reported HIV risk indicators at 1 year (overall, among non-PrEP initiators, and among PrEP initiators): transactional sex, ≥6 sexual partners, unprotected sex with ≥3 partners, sex while drunk, and sexually transmitted infection diagnosis/treatment. Percentage differences ranged from 10% for individuals reporting at least six sexual partners to 30% for those reporting unprotected sex with three or fewer sexual partners. There was weak evidence of association between female gender and unchanged/increased HIV risk at 1 year (adjusted OR: 1.35, 95% CI (0.84-2.17)). No other indicators, including PrEP use, were associated with unchanged/increased HIV risk at 1 year. CONCLUSION: Regular risk-reduction counselling may reduce risky sexual behaviour, while PrEP initiation may not lead to risk compensation.

Predictors of Loss to Follow-Up in an HIV Vaccine Preparedness Study in Masaka, Uganda.

BACKGROUND: High participant retention is essential to achieve adequate statistical power for clinical trials. We assessed participant retention and predictors of loss to follow-up (LTFU) in an HIV vaccine-preparedness study in Masaka, Uganda. METHODS: Between July 2018 and March 2021, HIV sero-negative adults (18-45 years) at high risk of HIV infection were identified through HIV counselling and testing (HCT) from sex-work hotspots along the trans-African highway and fishing communities along the shores of Lake Victoria. Study procedures included collection of baseline socio-demographic data, quarterly HCT, and 6-monthly collection of sexual risk behaviour data. Retention strategies included collection of detailed locator data, short clinic visits (1-2 h), flexible reimbursement for transport costs, immediate (≤7 days) follow-up of missed visits via phone and/or home visits, and community engagement meetings. LTFU was defined as missing ≥2 sequential study visits. Poisson regression models were used to identify baseline factors associated with LTFU. RESULTS: 672 participants were included in this analysis. Of these, 336 (50%) were female and 390 (58%) were ≤24 years. The median follow-up time was 11 months (range: 0-31 months). A total 214 (32%) participants were LTFU over 607.8 person-years of observation (PYO), a rate of 35.2/100 PYO. LTFU was higher in younger participants (18-24 years versus 35-45 years, adjusted rate ratio (aRR) = 1.29, 95% confidence interval (CI) 0.80-2.11), although this difference was not significant. Female sex (aRR = 2.07, 95% CI, 1.51-2.84), and recreational drug use (aRR = 1.61, 95% CI, 1.12-2.34) were significantly associated with increased LTFU. Engagement in transactional sex was associated with increased LTFU (aRR = 1.36, 95% CI, 0.97-1.90) but this difference was not significant. LTFU was higher in 2020-2021 (the period of COVID-19 restrictions) compared to 2018-2019 (aRR = 1.54, 1.17-2.03). Being Muslim or other (aRR = 0.68, 95% CI 0.47-0.97) and self-identification as a sex worker (aRR = 0.47, 95% CI, 0.31-0.72) were associated with reduced LTFU. CONCLUSION: We observed a high LTFU rate in this cohort. LTFU was highest among women, younger persons, recreational drug users, and persons who engage in transactional sex. Efforts to design retention strategies should focus on these subpopulations.

Determinants and reasons for switching anti-retroviral regimen among HIV-infected youth in a large township of South Africa (2002-2019).

BACKGROUND: There are limited data exploring antiretroviral therapy (ART) changes and time to change among South Africa young people living with HIV/AIDS. OBJECTIVE: We describe the time to first drug switch, which includes ART regimen change (three drug switch) and substitutions (single drug switch). We describe common reasons for ART switch among young people aged 10 to 24 years in South Africa. METHODS: We conducted a retrospective cohort study at a primary health care clinic in Cape Town, South Africa, providing ART to HIV-infected adolescents and adults since 2002. Those aged 10 to 24 years at ART initiation, who accessed care clinic between September 2002 and April 2019. Data was retrieved from electronic information systems: ART regimens, ART changes, dates for initiation or stop of each drug/regimen, laboratory results (viral loads, haemoglobin, liver enzyme results, and creatinine to support the reason for ART switch. From written records, we abstracted reason for single drug switch or regimen change, as well as socio demographic and clinical data. We fitted cox regression models to determine factors associated with ART switch (Having a change in one or more drugs in ART combination) and the rate of occurrence. RESULTS: Of 2601 adolescents included, 605 (24.9%) adolescents switched ART over 5090.5 person years at risk (PYAR), a rate of 11.9 /100PYAR. Median follow-up time was 4.4 (± 3.2) years. At multivariable analysis, the older age group was protective of the risk of ART switch: adjusted Hazard Ratio [aHR] 0.78, 95% CI 0.62-0.98, transfer status [transferred out 1.42 [1.11-1.82]. The hazard of ART switch increased with more severe HIV-disease at ART start, as observed by increasing WHO clinical stage or reduced CD4 count at baseline. The primary reasons for ART switch were side effects (20.0%), virological failure (17.9%) and formulation switch (27.8%). Others reasons included pregnancy, Hepatitis B, tuberculosis and psychosis. CONCLUSION: ART switches are frequent and occur at a consistent rate across 7.5 years from initiation. The main reasons for ART switch were virological failure and drug side effects.

Assessment of risk compensation following use of the dapivirine vaginal ring in southwestern Uganda.

OBJECTIVES: Participation in HIV prevention trials could trigger risk compensation among participants. We evaluated potential risk compensation following use of a vaginal ring microbicide by women in a phase III trial in southwestern Uganda. METHODS: We used markers of sexual risk behaviour documented on standardised questionnaires, tested for STIs at baseline and quarterly for 2 years. Risk compensation was defined as a significant increase (trend p<0.05) in the proportion of women reporting risky sexual behaviour or a diagnosed STI between baseline and end of follow-up. RESULTS: Between September 2013 and December 2016, 197 women (active arm: n=132 and placebo: n=65) were enrolled at the Masaka site. There were decreases in all markers of sexual risk behaviour with statistically significant decreases in only the proportion of women reporting ≥2 sexual partners, p=0.026 and those diagnosed with Trichomonas vaginalis p<0.001 and or Neisseria gonorrhoeae p<0.001 CONCLUSIONS: No evidence of risk compensation was observed in this trial. TRIAL REGISTRATION NUMBER: NCT01539226.

The dapivirine vaginal ring from the perspective of married men in Uganda.

Background: Men play a key role in influencing uptake of women's health products, such as female condoms and vaginal microbicides used for family planning and HIV prevention.Method: We explored men's perceptions of the dapivirine vaginal ring (DVR), a vaginal microbicide, in Kalungu District, rural south-western Uganda. In June/July 2018, we conducted in-depth interviews with 10 partners of women participating in the DREAM study, a phase 3B open-label extension trial of the DVR. Data were analysed thematically, drawing on the socio-ecological model theoretical framework.Results: Influencing factors such as individual and interpersonal characteristics, perception of HIV risk, lack of knowledge about the DVR, misconceptions, and product characteristics acting at different levels (individual, societal and organisational) affected men's knowledge, attitudes and perceptions towards the DVR, which in turn impacted on their willingness to allow their partners to use it. Above all, men wanted to be involved in the decision- making process about the use of the DVR. All the men were happy that there was a new HIV prevention option in the pipeline and were not concerned about the degree of effectiveness, saying it was better than nothing.Conclusion: The use of the DVR in an environment where men expect to make decisions about sex on behalf of women may affect its usage and success. Given this context, women may not always be able to independently choose to use it. If the DVR is approved and rolled out, increased sensitisation of men about it will be critical to ensure its uptake.