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Background: Some HIV prevention research participants may hold a "preventive misconception" (PM), an overestimate of the probability or level of personal protection afforded by trial participation. However, these reports typically rely upon small, retrospective qualitative assessments that did not use a standardized approach. Methods: We administered a measure of PM called PREMIS, during Microbicide Trials Network 020—A Study to Prevent Infection with a Ring for Extended Use, a large, multicenter, placebo-controlled, phase III trial evaluating the safety and efficacy of a dapivirine vaginal ring among women at risk for HIV infection in Malawi, South Africa, Uganda, and Zimbabwe. The maximum follow-up period was 2.6 years. Results: One thousand two hundred sixty-one respondents completed PREMIS at their month 3 visit (M3); 2085 at their month 12 visit (M12); and 1010 at both visits. Most participants expressed high expectations of personal benefit (EPB) and that at least one of the rings used in the trial would reduce the risk of getting HIV (expectation of maximum aggregate benefit or EMAB). There was a moderate positive correlation between EPB and EMAB at M3 (r =.43, 95% CI:.37,.47) and M12 (r =.44, 95% CI:.40,.48). However, there was variability among sites in the strength of the relationship. There was no relationship between either expectation variable and condom use, adherence, or HIV infection. Conclusions: A majority of trial participants expressed some belief that their risk of HIV infection would be reduced by using a vaginal ring, which may signal PM. However, such beliefs were not associated with adherence, condom use, or subsequent HIV infection, and there was variability across sites. Further work is needed to understand these findings. [ABSTRACT FROM AUTHOR]

Understanding how women use PrEP is important for developing successful implementation programs. We hypothesized there are distinct patterns of adherence, related to HIV risk and other factors. We identified patterns of PrEP adherence and HIV risk behavior over the first 6 months of PrEP use, using data from 233 HIV-uninfected women in high-risk serodiscordant couples in a demonstration project in Kenya & Uganda. We modeled PrEP adherence, assessed by daily electronic monitoring, and HIV risk behavior using group-based trajectory models. We tested baseline covariates and risk behavior group as predictors of adherence patterns. There were four distinct adherence patterns: high steady adherence (55% of population), moderate steady (29%), late declining (8%), and early declining (9%). No baseline characteristics significantly differed between adherence patterns. Adherence patterns differed in average weekly doses (6.7 vs 5.4 vs 4.1 vs 1.5, respectively). Two risk behavior groups were identified: steady HIV risk (78% of population) and declining (22%). Compared to women with declining HIV risk behavior, women with steady risk behavior were more likely to have high steady adherence (61% vs 35%) and less likely to have early (6% vs 17%) or late (4% vs 19%) declining adherence. Women’s use of PrEP was associated with concurrent HIV risk behavior; higher risk was associated with higher, sustained adherence. [ABSTRACT FROM AUTHOR]

Background: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation., Methods: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037., Findings: Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR., Interpretation: High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa., Funding: The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Understanding how women use PrEP is important for developing successful implementation programs. We hypothesized there are distinct patterns of adherence, related to HIV risk and other factors. We identified patterns of PrEP adherence and HIV risk behavior over the first 6 months of PrEP use, using data from 233 HIV-uninfected women in high-risk serodiscordant couples in a demonstration project in Kenya & Uganda. We modeled PrEP adherence, assessed by daily electronic monitoring, and HIV risk behavior using group-based trajectory models. We tested baseline covariates and risk behavior group as predictors of adherence patterns. There were four distinct adherence patterns: high steady adherence (55% of population), moderate steady (29%), late declining (8%), and early declining (9%). No baseline characteristics significantly differed between adherence patterns. Adherence patterns differed in average weekly doses (6.7 vs 5.4 vs 4.1 vs 1.5, respectively). Two risk behavior groups were identified: steady HIV risk (78% of population) and declining (22%). Compared to women with declining HIV risk behavior, women with steady risk behavior were more likely to have high steady adherence (61% vs 35%) and less likely to have early (6% vs 17%) or late (4% vs 19%) declining adherence. Women's use of PrEP was associated with concurrent HIV risk behavior; higher risk was associated with higher, sustained adherence.

Background: Starting lifelong antiretroviral therapy (ART) in HIV-infected pregnant women may decrease HIV progression and transmission, but adherence after delivery may be difficult, especially for asymptomatic women. We evaluated disease progression among HIV-infected women not on ART with CD4⁺ lymphocyte counts above 200 cells per microliter at delivery., Methods: We analyzed risk of death, progression to AIDS (stage IV or CD4 < 200 cells per microliter), or to CD4⁺ count <350 1 year after delivery among postpartum women enrolled to a prevention of breastfeeding transmission trial using the Kaplan-Meier method. In the primary analysis, women were censored if ART was initiated., Results: Among 1285 women who were not WHO stage IV or less at 6 weeks postpartum, 49 (4.3%) progressed to stage IV/CD4 <200 cells per microliter or death by 1 year. Progression to CD4 <200 cells per microliter or death occurred among 16 (4.3%) of 441 women with CD4 count of 350-549 cells per microliter and 10 (1.6%) of 713 with CD4 counts >550 cells per microliter at delivery. CD4 <350 cells per microliter by 12 months postpartum occurred among 116 (37.0%) of 350 women with CD4 count 400-549 cells per microliter and 48 (7.4%) of 713 with CD4 count >550 cells per microliter at delivery., Conclusions: Progression to AIDS or CD4 count <350 cells per microliter is uncommon through 1 year postpartum for women with CD4 counts over 550 cells per microliter at delivery, but occurred in over one third of those with CD4 counts under 550 cells per microliter. ART should be continued after delivery or breastfeeding among women with CD4 counts <550 cells per microliter if follow-up and antiretroviral adherence can be maintained.

Background: The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis., Methods: HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables., Results: NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003)., Conclusions: Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.

Objective: Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed., Design: Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1., Methods: Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole + nevirapine and the cotrimoxazole + placebo groups were compared using negative-binomial regression., Results: Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole + nevirapine and cotrimoxazole + placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole + nevirapine versus cotrimoxazole + placebo., Conclusion: Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.

Objectives: To determine the utility of total lymphocyte count (TLC) in predicting the 12-month mortality in HIV-infected Ugandan children and to correlate TLC and CD4 cell %., Design: This is a retrospective data analysis of clinical and laboratory data collected prospectively on 128 HIV-infected children in the HIV Network for Prevention Trials 012 trial., Methods: TLC and CD4 cell % measurements were obtained at birth, 14 weeks, and 12, 24, 36, 48, and 60 months of age and assessed with respect to risk of death within 12 months., Results: Median TLC per microliter (CD4 cell %) was 4150 (41%) at birth, 4900 (24%) at 12 months, 4300 (19%) at 24 months, 4150 (19%) at 36 months, 4100 (18%) at 48 months, and 3800 (20%) at 60 months. The highest risk of mortality within 12 months was 34% - 37% at birth and declined to 13%-15% at 24 months regardless of TLC measurement. The correlation between CD4 cell % and TLC was extremely low overall (r = 0.01)., Conclusions: The TLC did not predict a risk of progression to death within 12 months in HIV-infected Ugandan children. Therefore, TLC alone may not be a useful surrogate marker for determining those children at highest risk of death, who require antiretroviral therapy most urgently.