Efficacy of the Dapivirine Vaginal Ring Accounting for Imperfect Adherence.

Product adherence is critical to obtaining objective estimates of efficacy of pre-exposure prophylactic interventions against HIV-1 infection. With imperfect adherence, intention-to-treat analyses assess the collective effects of complete, sub-optimal and non-adherence, providing a biased and attenuated estimate of the average causal effect of an intervention. Using data from the MTN-020/ASPIRE phase III trial evaluating HIV-1 efficacy of the dapivirine vaginal ring, we conducted per-protocol, and adherence-adjusted causal inference analyses using principal stratification and marginal structural models. We constructed two adherence cut offs of ≥ 0.9 mg (low cutoff) and > 4.0 mg (high cutoff) that represent drug released from the ring over a 28-day period. The HIV-1 efficacy estimate (95% CI) was 30.8% (3.6%, 50.3%) (P = 0.03) from the per-protocol analysis, and 53.6% (16.5%, 74.3%) (P = 0.01) among the highest predicted adherers from principal stratification analyses using the low cutoff. Marginal structural models produced efficacy estimates (95% CIs) ranging from 48.8 (21.8, 66.4) (P = 0.0019) to 56.5% (32.8%, 71.9%) (P = 0.0002). Application of adherence-adjusted causal inference methods are useful in interpreting HIV-1 efficacy in secondary analyses of PrEP clinical trials.

Reliability and Validation of the PFIQ-7 and PFDI-20 in the Luganda Language.

INTRODUCTION AND HYPOTHESIS: Pelvic floor disorders (PFDs) impact women worldwide and are assessed using instruments such as the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7). There are no known valid PFD instruments in Uganda. This study's purpose was to translate and test the reliability and validity of the PFDI-20 and PFIQ-7 in Luganda. It was predicted that these instruments would be reliable and valid to assess the presence and impact of PFD in parous Luganda-speaking women. METHODS: The translated PFDI-20 and PFIQ-7 were administered to parous Luganda-speaking women and readministered 4-8 months after. The Pelvic Organ Prolapse Quantification (POP-Q) examination determined the presence of pelvic organ prolapse (POP) and a cough-stress test (CST) measured urinary leakage. Analysis was completed using Cronbach's α co-efficient for internal consistency and Spearman's correlation coefficients and Wilcoxon rank sum tests for construct validity. RESULTS: Of the 159 participants, 93 (58.3%) had stage II POP or higher. The PFDI-20 and PFIQ-7 demonstrated minimal bother and impact on activities of daily living respectively. The Urinary Distress Inventory 6 (UDI-6) scores on the PFDI-20 showed a strong positive association with the presence of urinary incontinence. When PFD was defined by responses to symptom assessment, the translated PFDI-20 and PFIQ-7 could differentiate between individuals with and without PFD. CONCLUSIONS: The UDI-6 section of the PFDI-20 was found to be valid in Luganda. The PFIQ-7 and the entirety of the PFDI-20 were not found to be reliable or valid, likely because of the low prevalence of PFDs in the study population.

Association Between Physical Activity and Pelvic Floor Disorders in Parous Ugandan Women.

INTRODUCTION AND HYPOTHESIS: The aim was to assess the association between the degree of physical activity (PA) and the presence of pelvic floor disorders (PFDs) in a cohort of parous Ugandan women. METHODS: In this cross-sectional study, PFDs were measured using symptom assessment, standardized questionnaires (Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire), and a standardized physical examination (POP-Q and cough stress test [CST]). Degree of PA was assessed using the International Physical Activity Questionnaire. Interquartile ranges were used to describe the age, parity, and body mass index (BMI) of participants. To examine the association between PA and PFDs, a log transformation was applied to the weekly minutes of PA variable and a logistic regression model was constructed with weekly minutes of moderate/vigorous PA, age, BMI, and parity as the predictors. RESULTS: A total of 159 women were enrolled. Median age was 35 (IQR 32-37), median parity 4 (IQR 3-5), and median BMI 29.0 (IQR 24-33). The prevalence of PFD as determined by symptom assessment was 28% (n=44). The most frequent stage of prolapse identified by POP-Q was stage II (57%, n=91). Thirty-six percent of the women (n=58) reported vigorous PA. Ninety-nine percent of the cohort (n=158) reported moderate PA. When controlling for age, parity, and BMI there was a significant positive association between PFD (defined as a combination of stage II prolapse, positive CST, and urinary incontinence (UI)) and moderate PA (OR 2.20, 95% CI 1.08-5.14, p value 0.045). CONCLUSIONS: Pelvic floor disorders are common among parous Ugandan women and are associated with moderate PA when controlling for age, BMI, and parity. Understanding the risk factors associated with PFD in this population may better equip providers to screen and care for individuals.

Factors associated with willingness to use oral pre-exposure prophylaxis (PrEP) in a fisher-folk community in peri-urban Kampala, Uganda.

BACKGROUND: The World Health Organization (WHO) recommends the use of pre-exposure prophylaxis (PrEP) in key populations at elevated risk for exposure to HIV. If used effectively, PrEP can reduce annual HIV incidence to below 0.05%. However, PrEP is not acceptable among all communities that might benefit from it. There is, therefore, a need to understand perceptions of PrEP and factors associated with willingness to use PrEP among key populations at risk of HIV, such as members of communities with exceptionally high HIV prevalence. OBJECTIVE: To examine the perceptions and factors associated with willingness to use oral PrEP among members of fishing communities in Uganda, a key population at risk of HIV. METHODS: We conducted an explanatory sequential mixed-methods study at Ggaba fishing community from February to June 2019. Survey data were collected from a systematic random sample of 283 community members in which PrEP had not been rolled out yet by the time of we conducted the study. We carried out bivariate tests of association of willingness to use PrEP with demographic characteristics, HIV risk perception, HIV testing history. We estimated prevalence ratios for willingness to use PrEP. We used backward elimination to build a multivariable modified Poisson regression model to describe factors associated with willingness to use PrEP. We purposively selected 16 participants for focus group discussions to contextualize survey findings, analysing data inductively and identifying emergent themes related to perceptions of PrEP. KEY RESULTS: We enrolled 283 participants with a mean age of 31 ± 8 years. Most (80.9%) were male. The majority of participants had tested for HIV in their lifetime, but 64% had not tested in the past 6 months. Self-reported HIV prevalence was 6.4%. Most (80.6, 95%CI 75.5-85.0) were willing in principle to use PrEP. Willingness to use PrEP was associated with perceiving oneself to be at high risk of HIV (aPR 1.99, 95%CI 1.31-3.02, P = 0.001), having tested for HIV in the past 6-months (aPR 1.13, 95%CI 1.03-1.24, P = 0.007), and completion of tertiary education (aPR 1.97, 95%CI 1.39-2.81, P < 0.001). In focus group discussions, participants described pill burden, side-effects and drug safety as potential barriers to PrEP use. CONCLUSIONS AND RECOMMENDATIONS: Oral PrEP was widely acceptable among members of fishing communities in peri-urban Kampala. Programs for scaling-up PrEP for fisherfolk should merge HIV testing services with sensitization about PrEP and also increase means of awareness of PrEP as an HIV preventive strategy .

Correlates of Adherence to the Dapivirine Vaginal Ring for HIV-1 Prevention.

Understanding characteristics associated with adherence to pre-exposure prophylaxis (PrEP) methods for HIV-1 prevention may assist with optimizing implementation efforts. The dapivirine vaginal ring is a novel topical PrEP delivery method. Using data from a randomized, double-blind, placebo-controlled, phase III trial of the dapivirine vaginal ring conducted in four African countries, generalized estimating equation models were used to evaluate correlates of ring adherence. Two levels of quarterly dapivirine blood plasma, and dapivirine released from returned rings defined measures of adherence for recent and cumulative use, respectively. Time on study, calendar time, primary partner knowledge that the participant was taking part in the study, and use of long-acting contraceptive methods were associated with ring adherence whereas younger age, ring worries, condom use, episodes of menstrual bleeding and vaginal washing were associated with non-adherence. These findings may be useful for recruitment into future clinical studies and dapivirine ring implementation efforts.

Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda.

INTRODUCTION: Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations (VF-M) is on the rise. However, there is a paucity of information on the factors associated with this observation in low-income countries. Knowledge of underlying factors is critical if we are to minimize the number of PLHIV switched to costly third-line ART. Our study investigated the factors associated with VF-M. METHODS: We conducted a matched case-control analysis of patients' records kept at the Joint Clinical Research Center, starting from January 2008 to May 2018. We matched records of patients who failed the second-line ART with major PI mutations (cases) with records of patients who were virologically suppressed (controls) by a ratio of 1:3. Data analysis was conducted using STATA Version 14. Categorical variables were compared with the outcomes failure on second-line ART with PI mutations using the Chi-square and Fisher's exact tests where appropriate. Conditional logistic regression for paired data was used to assess the association between the outcome and exposure variables, employing the backward model building procedure. RESULTS: Of the 340 reviewed patients' records, 53% were women, and 6.2% had previous tuberculosis treatment. Males (aOR = 2.58, [CI 1.42-4.69]), and patients concurrently on tuberculosis treatment while on second-line ART (aOR = 5.65, [CI 1.76-18.09]) had higher odds of VF-M. ART initiation between 2001 and 2015 had lower odds of VF-M relative to initiation before the year 2001. CONCLUSION: Males and patients concomitantly on tuberculosis treatment while on second-line ART are at a higher risk of VF-M. HIV/AIDS response programs should give special attention to this group of people if we are to minimize the need for expensive third-line ART. We recommend more extensive, explorative studies to ascertain underlying factors.

Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study.

BACKGROUND: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. METHODS: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Residual dapivirine remaining in the last ring returned by each participant was used to estimate drug released from the ring, which was then adjusted for time participants had the ring to calculate probable use categorized into three levels (low/intermittent/high). Product use was connected to PEA attendance using participant identification numbers. We used multivariate Poisson regression with robust standard errors to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. RESULTS: 2312 of 2629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (RR = 1.40) than those who never attended an event. There was a stronger correlation between a last returned ring showing use and participant attendance at multiple events (RR = 1.52). CONCLUSIONS: Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE.

This analysis compares self-reports of product use with objective measures of non-adherence-quarterly plasma dapivirine levels and monthly residual dapivirine (DPV) levels in used rings-in MTN-020/ASPIRE, a phase 3 trial of a monthly DPV vaginal ring among women aged 18-45 years in Malawi, South Africa, Uganda and Zimbabwe. For participants on active product (N = 1211) we assessed self-reported monthly non-adherence, as measured by (1) whether the ring was ever out, and out for ≥ 12 h in the previous month and, (2) by a self-rating scale assessing ability to keep the vaginal ring inserted, and compared the self-reports to two biomarkers of non-use separately and as a composite measure. For this analysis, a plasma DPV value ≤ 95 pg/ml and residual ring ≥ 23.5 mg were used to classify non-adherence (i.e. the ring never being in the vagina the previous month). Compared to self-reports, non-adherence was found to be substantially higher for the composite measure as well as its two components, an indication that ring removal was likely underreported in the trial. The discrepancy between the self-report measure of ring outage and the composite indicator was greater for those aged 18-21 than for those older, evidence that younger women are more likely to underreport non-adherence. Despite underreporting of non-adherence, self-reports of the ring never being out were significant in predicting the composite objective measure. Furthermore, the association between the self-rating scale and the objective measure was in the expected direction and significant, although 11% of those 18-21 and 7% of those 22+ who rated their ability to keep the ring inserted as good, very good or excellent in the 4 weeks prior to exit were considered non-adherent according to the objective measure. This analysis indicates that while self-reports are significantly associated with objective measures of adherence in the ASPIRE trial, they were inflated-more so by those younger-and therefore may have limited utility identifying those who have challenges using products as directed. ClinicalTrials.gov number NCT01617096.

Perceived risk versus objectively measured risk of HIV acquisition: a cross-sectional study among HIV-negative individuals in Serodiscordant partnerships with clients attending an Urban Clinic in Uganda.

BACKGROUND: Acceptability of Pre-exposure Prophylaxis (PrEP) could be hampered by low self-perceived risk for HIV acquisition. Moreover, discordance between risk perception and actual risk of HIV acquisition is likely to occur. We assessed congruence between the level of self- perceived and that of objectively scored risk of HIV acquisition among HIV-negative individuals in discordant relationships. METHODS: This was a cross-sectional study among a representative sample of HIV-negative adult males and females whose partners were receiving antiretroviral therapy for at least 3 months from the Infectious Diseases Institute Clinic in Kampala, Uganda. Perceived risk was measured based on self-report using a numerical rating scale whereas objective risk was measured using a validated risk score tool. Congruence between perceived risk and objectively scored risk was evaluated using descriptive statistics and validity measures. Incongruence between the two phenomena was further evaluated using univariate and multivariate regression analyses. RESULTS: HIV-negative partners evaluated in this study were mostly male (64%) with a median age of 41 years (IQR 35 to 50). Majority (76.3%) of the partners perceived themselves as low risk for HIV acquisition. Similarly, most (93.8%) were objectively scored as low risk. However, nearly three quarters (72.7%) of partners who were objectively scored as high risk perceived themselves as being at low risk and all were men. The sensitivity and specificity of perceived risk for detecting the objectively measured risk was 27.3 and 76.5% respectively; area under ROC curve = 0.52; 95%CI (0.38, 0.66). The proportion of participants at high risk of HIV acquisition who perceived their risk as low was greater among those whose partners had detectable viral load compared to participants whose partners had undetectable viral load (PR = 0.51; 95%CI 0.29 to 0.90). CONCLUSION: Incongruence between perceived and objectively measured risk of HIV acquisition does occur especially among individuals whose partners had a detectable viral load. PrEP counselling for serodiscordant couples should focus on explaining the consequence of detectable viral load in the HIV-positive partner on HIV transmission risk.

"The number of clients is increasing but the supplies are reducing": provider strategies for responding to chronic antiretroviral (ARV) medicines stock-outs in resource-limited settings: a qualitative study from Uganda.

BACKGROUND: Despite the increasing frequency of ARV medicines stock-outs in Sub-Saharan Africa, there is little research inquiring into the mitigation strategies devised by frontline health facilities. Many previous studies have focused on 'upstream' or national-level drivers of ARVs stock-outs with less empirical attention devoted 'down-stream' or at the facility-level. The objective of this study was to examine the strategies devised by health facilities in Uganda to respond to the chronic stock-outs of ARVs. METHODS: This was a qualitative research design nested within a larger mixed-methods study. We purposively selected 16 health facilities from across Uganda (to achieve diversity with regard to; level of care (primary/ tertiary), setting (rural/urban) and geographic sub-region (northern/ central/western). We conducted 76 Semi-structured interviews with ART clinic managers, clinicians and pharmacists in the selected health facilities supplemented by on-site observations and documentary reviews. Data were analyzed by coding and thematic analyses. RESULTS: Participants reported that facility-level contributors to stock-outs include untimely orders of drugs from suppliers and inaccurate quantification of ARV medicine needs due to a paucity of ART program data. Internal stock management solutions for mitigating stock-outs which emerged include the substitution of ARV medicines which were out of stock, overstocking selected medicines and the use of recently expired drugs. The external solutions for mitigating stock-outs which were identified include 'borrowing' of ARVs from peer-providers, re-distributing stock across regions and upward referrals of patients. Systemic drivers of stock-outs were identified. These include the supply of drugs with a short shelf life, oversupply and undersupply of ARV medicines and migration pressures on the available ARVs stock at case-study facilities. CONCLUSION: Health facilities devised internal stock management strategies and relied on peer-provider networks for ARV medicines during stock-out events. Our study underscores the importance of devising interventions aimed at improving Uganda's medicines supply chain systems in the quest to reduce the frequency of ARV medicines stock-outs at the front-line level of service delivery. Further research is recommended on the effect of substituting ARV medicines on patient outcomes.

Low knowledge levels and high willingness to use oral Pre-Exposure Prophylaxis (PrEP) among Key Populations in Kampala, Uganda: Implications for targeted educational interventions.

Background: Preexposure prophylaxis (PrEP) reduces new human immunodeficiency virus(HIV) infections by up to 96% and is recommended for key populations by the World Health Organization. Understanding the knowledge and willingness to use PrEP is essential for effective implementation. This study assessed these factors and identifiedcharacteristics associated with differences in knowledge among key populations in Kampala, Uganda. Methods: We administered a cross-sectional survey to a systematic sample of 497 participants from fisherfolk (283, 56.9%), men who have sex with men (MSM) (93, 18.7%), and female sex worker (FSW) (121, 24.4%) communities in Kampala Central, where PrEP had not yet been rolled out. Data on sociodemographic characteristics, PrEP awareness, and HIV-related behavioralfactors were collected. Knowledge about PrEP was measured using an adopted questionnaire comprising five key questions about PrEP knowledge, graded as no knowledge, some knowledge and good knowledge. Ordered probit regression models were used to analyze the associations of independent factors with PrEP knowledge levels. Results: Participants had a mean age of 29±7.6 years. Ofthese, 257 (51.7%) reported having sex with women, 157 (31.6%) with men and 83 (16.7%) with both men and women. Self-reported HIV-positive status was 6.4% in fisherfolk, 11.8% in MSM and 27.3% in FSW. PrEP awareness stood at 62.4% overall, with the highest awareness in FSW (73.6%) and the lowest in fisherfolk (54.1%). Willingness to use PrEP was high across all groups (77.7%), although it was lower among FSW (66.9%). Multivariate probit analysis highlighted key independent factors associated with PrEP knowledge among fisherfolks and HIV-related concerns (Adj. Coeff = 0.54, 95% CI: 0.11, 0.97) and lack of PrEP awareness (Adj. Coeff = -0.99, 95% CI:-1.28, -0.70); among MSM, lack of PrEP awareness (Adj. Coeff = -1.74, 95% CI:-2.38, -1.10); and in FSW, tertiary education (Adj. Coeff = 1.53, 95% CI: 0.07, 2.99) and marital status (Adj. Coeff = 0.57, 95% CI=0.09, 1.05). MEshighlighted the influence of these independent factors at each knowledge level. Conclusions and Recommendations: Despite the high willingness to use PrEP, significant knowledge gaps exist, particularly concerning dosage and use duration, which are influenced by factors such as HIV concern and educational attainment. Tailored educational initiatives may bridge these gaps and enhance willingness to use PrEP.

Pelvic floor disorder prevalence and risk factors in a cohort of parous Ugandan women.

OBJECTIVES: The aim of this study was to determine the prevalence of pelvic floor disorders (PFDs) and associated risk factors among parous Ugandan women. METHODS: We performed a cross-sectional study of parous Ugandan women. Demographics and assessment for PFD were obtained. The presence of PFD was defined by participant symptom report, standardized questionnaires, and standard physical examination (pelvic organ prolapse quantification [POP-Q] and cough stress test [CST]). RESULTS: A total of 159 women were enrolled in the study between June 2022 and June 2023. The median age was 35 years and median parity was 4. Forty-four (28%) women in the cohort reported symptoms of urinary incontinence. No women reported symptoms of pelvic organ prolapse or anal incontinence. Seventy-two (46%) participants had a positive CST and 93 (58.3%) had stage II or greater prolapse based on the POP-Q. Cesarean section was found to have a protective effect for the development of PFD (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.59, P = 0.004). CONCLUSION: PFDs are prevalent among parous Ugandan women at rates similar to cohorts in other low- and middle-income countries. Cesarean section seems to be a protective factor against developing PFDs.

Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus: A Randomized Controlled Trial.

OBJECTIVE: To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. METHODS: The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. RESULTS: Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. CONCLUSION: Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01061151.

Community Health Workers Improve HIV Disclosure Among HIV-Affected Sexual Partners in Rural Uganda: A Quasi-Experimental Study.

BACKGROUND: We evaluated the efficacy of a community health worker (CHW)-led intervention in supporting disclosure among adults living with HIV in heterosexual relationships. METHODS: We conducted a quasi-experimental study with 2 arms allocated by geographically determined clusters and adjusted for between-group differences among adults living with HIV in the greater Luwero region of Uganda who had never disclosed their status to their current primary sexual partners. Clusters were allocated to either a CHW-led intervention or a control arm. In both arms, participants were consecutively recruited. As opposed to receiving routine care for the control arm, participants in the intervention arm received additional CHW disclosure support. The overall follow-up was 6 months, and the primary outcome was disclosure to the sexual partner. Data were analyzed using a clustered modified Poisson regression model with robust standard errors to determine independent factors associated with disclosure. RESULTS: Of the 245 participants who enrolled, 230 (93.9%) completed the study, and 112 (48.7%) of those were in the intervention arm. The median age was 30 (interquartile range=25-37) years, the majority were women (76.5%), and most (80%) did not know their partners' HIV status at study entry. At the end of follow-up, the overall disclosure prevalence was 74.4% (95% confidence interval [CI]=68.2, 79.9) and participants in the intervention arm were 51% more likely to disclose compared to those in the control (adjusted relative ratio [aRR]=1.51; 95% CI=1.28, 1.77). Men were 24% (aRR=1.24; 95% CI=1.07, 1.44) more likely to disclose compared to women, and membership in an HIV/AIDS association increased disclosure by 18% (aRR=1.18; 95% CI=1.01, 1.39). CONCLUSION: CHW support improved disclosure among adults living with HIV in heterosexual relationships when compared to routine care. Therefore, CHW-led mechanisms may be utilized in increasing disclosure among adults living with HIV in heterosexual relationships in rural settings.

Brief Report: Impact of Antiretroviral Regimen on Pregnancy and Infant Outcomes in Women With HIV/ HBV Coinfection.

BACKGROUND: There are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV. METHODS: The PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly. RESULTS: Of 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ). CONCLUSION: With HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.

Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.

OBJECTIVE: We aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities. DESIGN: Secondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE). METHODS: Data from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo vaginal ring. We further assessed for the effect of the vaginal ring device on cervical cytology by comparing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population. RESULTS: Cervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo vaginal ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo vaginal ring arms (P = 0.24). CONCLUSION: These findings indicate that neither use of the dapivirine vaginal ring nor the vaginal ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.

Acquisition of Sexually Transmitted Infections among Women Using a Variety of Contraceptive Options: A prospective Study among High-risk African Women.

INTRODUCTION: In many African settings, women concurrently face substantial risk of human immunodeficiency virus type 1 (HIV-1) infection, sexually transmitted infections (STIs) and unintended pregnancies. Few studies have evaluated STI risk among users of hormonal implants and copper intrauterine devices (IUDs) although these long-acting reversible contraceptive methods are being promoted widely because of their benefits. Within a prospective study of women at risk for HIV-1, we compared the risk of acquisition of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women using different contraceptive methods. METHODS: MTN-020/ASPIRE was a randomized trial of the dapivirine vaginal ring for HIV-1 prevention among 2629 women aged 18 to 45 years from Malawi, South Africa, Uganda and Zimbabwe, of whom 2264 used copper IUDs or progestin-based injectables or implants during follow-up. Screening for the above STIs occurred semi-annually. RESULTS: Over 3440 person-years of follow-up, 408 cases of C. trachomatis (incidence 11.86/100 person-years), 196 of N. gonorrhoeae (5.70/100 person-years) and 213 cases of T. vaginalis (6.19/100 person-years) were detected. C. trachomatis and N. gonorrhoeae incidence were not significantly different across contraceptive methods. T. vaginalis incidence was significantly higher for copper IUD users compared to depot medroxyprogesterone acetate (DMPA), implant and norethisterone enanthate users. CONCLUSION: Among African women at high HIV-1 risk, STIs were common. Risk of cervical infections did not differ across contraceptive methods. Significantly higher rates of T. vaginalis were observed among progestin-based methods compared to copper IUD users. Overall, these findings call for more intensive routine screening for STIs, and they support current World Health Organization guidance that women should have a wide range of contraceptive options.

Brief Report: Dapivirine Vaginal Ring Use Does Not Diminish the Effectiveness of Hormonal Contraception.

OBJECTIVE: To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use. DESIGN: A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention. METHODS: Use of a highly effective method of contraception was an eligibility criterion for study participation. Urine pregnancy tests were performed monthly. Pregnancy incidence by arm was calculated separately for each hormonal contraceptive method and compared using an Andersen-Gill proportional hazards model stratified by site and censored at HIV-1 infection. RESULTS: Of 2629 women enrolled, 2310 women returned for follow-up and reported using a hormonal contraceptive method at any point during study participation (1139 in the dapivirine arm and 1171 in the placebo arm). Pregnancy incidence in the dapivirine arm versus placebo among women using injectable depot medroxyprogesterone acetate was 0.43% vs. 0.54%, among women using injectable norethisterone enanthate was 1.15% vs. 0%, among women using hormonal implants was 0.22% vs. 0.69%, and among women using oral contraceptive pills was 32.26% vs. 28.01%. Pregnancy incidence did not differ by study arm for any of the hormonal contraceptive methods. CONCLUSIONS: Use of the dapivirine ring does not reduce the effectiveness of hormonal contraceptives for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, potentially because of poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

INTRODUCTION: Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. METHODS: ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. RESULTS: Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. CONCLUSIONS: African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.