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Although digital health promotion (DHP) technologies for young people are increasingly available in low- and middle-income countries (LMICs), there has been insufficient research investigating whether existing ethical and policy frameworks are adequate to address the challenges and promote the technological opportunities in these settings. In an effort to fill this gap and as part of a larger research project, in November 2022, we conducted a workshop in Cape Town, South Africa, entitled 'Unlocking the Potential of Digital Health Promotion for Young People in Low- and Middle-Income Countries'. The workshop brought together 25 experts from the areas of digital health ethics, youth health and engagement, health policy and promotion and technology development, predominantly from sub-Saharan Africa (SSA), to explore their views on the ethics and governance and potential policy pathways of DHP for young people in LMICs. Using the World Café method, participants contributed their views on (i) the advantages and barriers associated with DHP for youth in LMICs, (ii) the availability and relevance of ethical and regulatory frameworks for DHP and (iii) the translation of ethical principles into policies and implementation practices required by these policies, within the context of SSA. Our thematic analysis of the ensuing discussion revealed a willingness to foster such technologies if they prove safe, do not exacerbate inequalities, put youth at the center and are subject to appropriate oversight. In addition, our work has led to the potential translation of fundamental ethical principles into the form of a policy roadmap for ethically aligned DHP for youth in SSA. [ABSTRACT FROM AUTHOR]

Although the use of the cluster randomized trial (CRT) design to evaluate vaccines, public health interventions or health systems is increasing, the ethical issues posed by the design are not adequately addressed, especially in low- and middle-income country settings (LMICs). To help reveal ethical challenges, qualitative interviews were conducted with key stakeholders experienced in designing and conducting two selected CRTs in Malawi. The 18 interviewed stakeholders included investigators, clinicians, nurses, data management personnel and community workers who were invited to share their experiences related to implementation of CRTs. Data analysis revealed five major themes with ethical implications: (1) The moral obligation for health care providers to participate in health research and its compensation; (2) Suboptimal care services compromising the integrity of CRT; (3) Ensuring scientific validity and withholding care service; (4) Obtaining valid consent and permission for waiver of consent; and (5) Inadequate risk assessment for trial participation. Understanding key ethical issues posed by CRTs in Malawi could improve ethical review and research oversight of this particular study design. [ABSTRACT FROM AUTHOR]

Purpose of Review: The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although DMPA-IM provides reliable contraception, potential effects on the female genital tract (FGT) mucosa have raised concern, including risk of HIV infection. This review summarises and compares evidence from observational cohort studies and the randomised Evidence for Contraceptive Options in HIV Outcomes (ECHO) Trial. Recent Findings: Although previous observational studies found women using DMPA-IM had higher abundance of bacterial vaginosis (BV)-associated bacteria, increased inflammation, increased cervicovaginal HIV target cell density, and epithelial barrier damage, sub-studies of the ECHO Trial found no adverse changes in vaginal microbiome, inflammation, proteome, transcriptome, and risk of viral and bacterial STIs, other than an increase in Th17-like cells. Summary: Randomised data suggest that DMPA-IM use does not adversely change mucosal endpoints associated with acquisition of infections. These findings support the safe use of DMPA-IM in women at high risk of acquiring STIs, including HIV. [ABSTRACT FROM AUTHOR]

Introduction: Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation. Methods: AGYW aged 16–21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months. Eligible AGYW were HIV-negative, not pregnant and using effective contraception for at least two months prior to enrollment. Descriptive statistics were used to summarize demographic and behavioral data while multinomial analysis was used to determine predictors of stated product preference (ring or oral PrEP). Results: Of the 247 AGYW enrolled in REACH, 34% were aged 16–17 and 89% had a primary partner.The median age of sexual debut was 16 years and 40% had ever been pregnant. At screening, 35% of participants were diagnosed with a sexually transmitted infection (STI), 39% had an AUDIT-C score associated with harmful drinking and 11% reported intimate partner violence in the past 6 months. Overall, 28% of participants, had CESD-10 scores suggestive of depressive symptoms (≥12) in the past week. At baseline, similar proportions stated a preference for the ring and oral PrEP (38.1% and 40.5% respectively), with 19% of participants stating they preferred both products equally. Only study site was significantly associated with product preference (P<0.05) with AGYW from Johannesburg having higher odds of preferring the ring and those from Kampala having higher odds of preferring both options equally. Conclusions: We successfully enrolled African AGYW with a clear unmet need for HIV prevention. The balanced preference between the two products suggests that multiple biomedical prevention options may be appealing to this age group and could address their prevention needs. [ABSTRACT FROM AUTHOR]

MTN-025/HOPE was an open-label trial of the dapivirine vaginal ring conducted in four African countries between 2016 and 2018. Women were first offered one ring monthly (at baseline, months 1 and 2), thereafter, transitioned to a more applicable real-world dispensation schedule, − 3 rings quarterly (at months 3, 6 and 9). Logistic regression analysis was used to assess correlates of ring acceptance at baseline and through follow-up. A total of 1456 women (median age 31 years) enrolled, 1342 (92.2%) accepted the ring at baseline and 1163 (79.9%) accepted the ring(s) at all visits. Changing ring dispensation from a monthly to a quarterly schedule had no negative effect on acceptance. Having a primary partner and him knowing about the ring being offered in HOPE, use of long-acting contraception (implants, injections, IUDs) or sterilization were associated with ring acceptance, along with prior strong intention to use the ring in the future. Efforts should consider these factors when rolling out the ring for HIV prevention. [ABSTRACT FROM AUTHOR]

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. We evaluated post-randomization sexual behavior using an objective marker of condomless vaginal sex in a subset of participants. We conducted a sub-study among 458 ECHO participants at three sites (Cape Town, Johannesburg, Kisumu) to evaluate the frequency of condomless vaginal sex, measured by prostate specific antigen (PSA) detection in vaginal swabs, collected at the month 6 and final visit and the concordance of self-reported condomless vaginal sex with PSA detection, by randomized arm. We compared PSA detection frequency and concordance of PSA and self-reported condomless vaginal sex, by randomized group using Cochran–Mantel–Haenszel tests and adjusted generalized logistic growth curve models. PSA was detected less frequently in the DMPA-IM (16%), compared to the Cu-IUD (21%) and LNG implant (24%) groups, although results were not statistically significant in the unadjusted model when accounting for pre-specified multiple-testing criteria. There were significant differences in PSA detection between the DMPA-IM and LNG-implant groups (odds ratio 0.61 (95% CI 0.40, 0.94) in the adjusted model. There was moderate discordance between self-reported condomless vaginal sex and detection of PSA that was similar across randomized groups. These data suggest that women randomized to Cu-IUD and LNG implant may have had condomless sex more frequently than women randomized to DMPA-IM. The discordance between detectable PSA and self-reported sexual behaviour has important implications for design of future HIV prevention studies. [ABSTRACT FROM AUTHOR]

Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays. Primary endpoints include incident BV occurrence, bacterial diversity, and bacterial and cytokine concentrations. Secondary endpoints are bacterial and cytokine concentrations associated with later HIV seroconversion. Participants randomized to Cu-IUD exhibit elevated bacterial diversity, increased cytokine concentrations, and decreased relative abundance of lactobacilli after one and six months of use, relative to enrollment and other contraceptive options. Total bacterial loads of women using Cu-IUD increase 5.5 fold after six months, predominantly driven by increases in the concentrations of several inflammatory anaerobes. Furthermore, growth of L. crispatus (MV-1A-US) is inhibited by Cu2+ ions below biologically relevant concentrations, in vitro. Our work illustrates deleterious effects on the vaginal environment induced by Cu-IUD initiation, which may adversely impact sexual and reproductive health.Here, in a randomized trial, the authors comparatively evaluate the effect of a copper intrauterine device versus other contraceptive options on the vaginal environment after one and six consecutive months of use, finding to exert changes on the vaginal microbiota that may potentially lead to detrimental sex and reproductive health. [ABSTRACT FROM AUTHOR]

Background: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls).Methods: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100).Results: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1β, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results.Conclusions: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk.Clinical Trials Registration: NCT02550067. [ABSTRACT FROM AUTHOR]

The article focuses on the ethical implications and challenges associated with big data research in the context of health data science. Topics include the blurring boundaries between clinical care and research, the need for community engagement to build trust and address participation barriers, and the limitations in current frameworks for community engagement in data science research.

The article focuses on the ethical implications of data science research, particularly in the context of big data and its use in healthcare. Topics discussed include the need for ethics review in data science research, challenges related to bias and privacy, the establishment of ethics advisory committees, and suggested reforms to improve the ethics review process.

Introduction: South Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition. Methods: During December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16–35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12–18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection. Results: 5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05–5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV. Conclusions: HIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population. Clinical trial registration: ClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites. [ABSTRACT FROM AUTHOR]

The article discusses the benefits of the electronic consent in a COVID-19 vaccine implementation trial in South Africa. Topics include participation of healthcare professionals (HCPs) in an online survey to explore their experiences of providing electronic consent for enrolment into the largest implementation trial of a COVID vaccine in South Africa; training of HCPs with access to electronic devices and data; and the use of descriptive analysis to characterise respondents.

Background: Cervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives. Methods: We collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis. Results: Cytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota. Conclusions: Both DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women's willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women's adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64–80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03–1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38–35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70–6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36–10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention. [ABSTRACT FROM AUTHOR]

Contraceptive adherence during acute and recent HIV-1 infection is important to maternal and child health given the elevated risk of vertical HIV-1 transmission and additional complications of pregnancy. Injectable contraception (IC) is the most common non-barrier modern contraception method used in sub-Saharan Africa (SSA). Adherence to IC after HIV-1 seroconversion is not well understood. We examined factors associated with IC discontinuation among women in SSA diagnosed with HIV-1 infection while participating in a clinical trial of biomedical HIV-1 prevention. After diagnosis with HIV-1 infection in the VOICE trial, 255 women from South Africa, Uganda, and Zimbabwe enrolled in a longitudinal observational study (MTN-015). Contraceptive method was assessed at MTN-015 baseline and at 3, 12, and 24 months post-seroconversion. Correlates of IC discontinuation were examined by Cox proportional hazard modeling. IC use was reported at baseline by 78% of women enrolled (198/255), of which 92% (182/198) completed at least one follow-up visit. Two-thirds of women (66%, 121/182) continued on IC during the follow-up period (median 24 months). Lower rates of IC discontinuation were observed in women who reported having had at least one child (HR 0.39, 95% CI 0.20-0.82) or earning a personal income (HR 0.51, 95% CI 0.30-0.87) at baseline. These findings suggest that many women with HIV-1 infection face complex decision-making regarding family planning in the years that follow seroconversion and highlight that some women may discontinue IC use despite on-site provision of family planning services. Understanding the broader context of family planning choices in recently seroconverted women may be key to more effective linkages between family planning services and HIV-1 testing and care. [ABSTRACT FROM AUTHOR]

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]

Background: Little is known regarding HIV disease outcomes among individuals who become infected with HIV while receiving antiretroviral medications for prevention. We compared HIV disease parameters among women who seroconverted while receiving tenofovir-containing oral or vaginal pre-exposure prophylaxis (PrEP) to placebo. Methods: Participants with HIV seroconversion in a randomized placebo-controlled trial of oral tenofovir, oral tenofovir/emtricitabine, and vaginal tenofovir gel (MTN-003) were followed in a longitudinal cohort study (MTN-015). The effect of oral and vaginal tenofovir-containing PrEP on HIV disease progression was compared to placebo using linear mixed effects and Cox proportional hazard models, as appropriate. Additional analyses were performed to compare the outcomes among participants with detectable tenofovir or emtricitabine in plasma at the first quarterly visit in MTN-003. Results: A total of 224 participants were included in the analysis; 93% from South Africa and 94% clade C virus. No differences in HIV RNA at steady state or the trajectory over 12 months were observed for each active arm compared to placebo; tenofovir gel recipients had higher CD4+ T cell counts (722 vs 596 cells/mm3; p = 0.02) at 90 days after estimated HIV seroconversion and higher average rates of change over 12 months compared to placebo (-181 vs -92 cells/mm3 per year; p = 0.08). With a median follow-up of 31 months, no significant differences were observed for time to CD4+ T cell count ≤350 cells/mm3, or the composite endpoint of CD4+ T cells ≤350 cells/mm3, initiation of antiretroviral therapy or death for each active arm compared to placebo. Additionally, there were no significant differences in the HIV RNA or CD4+ T cell counts at baseline, the change to month 12, or any disease progression outcomes among participants with oral drug detected and no oral drug detected compared to placebo. Conclusions: No clinically significant differences in HIV seroconversion outcomes were observed among women randomized to tenofovir-containing oral or vaginal PrEP regimens, however low overall adherence limits the generalizability of these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Wisebag™, a lunchbag-style container with an electronic events-monitoring system, was designed as a real-time indirect objective measure of microbicide gel use. Due to cost, alternative functionalities (i.e. use of offline and dummy versions) were explored. We conducted a three-arm, double-blinded pilot study among 50 HIV-negative women in Durban, South Africa to assess participant adherence and Wisebag acceptability and performance. Participants were randomized 2:2:1 to Wisebag with online (events transmitted via cellular signal in real-time), offline (events stored in device memory) or inactive 'dummy' devices. Participants were instructed to open the Wisebag daily for 2 weeks, retrieve a study sticker and affix it on a diary card. All participants completed the study. At exit, 94 % did not know which device they had received, nor could they differentiate the Wisebag types when presented with the three options. Five offline devices failed (no data recorded). Per Wisebag events, 26 % of women were perfectly adherent compared to 48 % by self-report and 46 % per diary card. Of reported non-adherence, 92 % did not open the Wisebag (travelling or forgot) and 22 % opened Wisebag >1×/day (curiosity). Participants liked and were comfortable carrying Wisebag. Successful blinding will allow inclusion of offline and/or dummy Wisebags in future study designs. Perfect adherence by opening events was significantly lower than by self-report, highlighting the importance of objective measures of adherence in clinical trials. Additional studies to validate Wisebag data with actual products, with and without SMS and online functionality, in different populations and settings, and in comparison to biomarkers are warranted. [ABSTRACT FROM AUTHOR]

Background: Concerns about the immune reconstitution inflammatory syndrome (IRIS) remain a barrier to antiretroviral therapy (ART) initiation during antituberculosis treatment in co-infected patients. Objective: To assess IRIS incidence, severity, and outcomes relative to the timing of ART initiation in patients with HIVrelated tuberculosis. Design: Randomized, open-label clinical trial. (ClinicalTrials.gov registration number: NCT00398996) Setting: An outpatient clinic in Durban, South Africa. Patients: 642 patients co-infected with HIV and tuberculosis. Measurements: In a secondary analysis of the SAPiT (Starting Antiretroviral Therapy at Three Points in Tuberculosis) trial, IRIS was assessed in patients randomly assigned to initiate ART within 4 weeks of tuberculosis treatment initiation (early integrated treatment group), within 4 weeks of completion of the intensive phase of tuberculosis treatment (late integrated treatment group), or within 4 weeks after tuberculosis therapy completion (sequential treatment group). The syndrome was defined as new-onset or worsening symptoms, signs, or radiographic manifestations temporally related to treatment initiation, accompanied by a treatment response. Severity of IRIS, hospitalization, and time to resolution were monitored. Results: Incidence of IRIS was 19.5 (n = 43), 7.5 (n = 18), and 8.1 (n = 19) per 100 person-years in the early integrated, late integrated, and sequential treatment groups, respectively. Among patients with a baseline CD4+ count less than 0.050 × 109 cells/L, IRIS incidence was 45.5, 9.7, and 19.7 per 100 person-years in the early integrated, late integrated, and sequential treatment groups, respectively. Incidence of IRIS was higher in the early integrated treatment group than in the late integrated (incidence rate ratio, 2.6 [95% CI, 1.5 to 4.8]; P < 0.001) or sequential (incidence rate ratio, 2.4 [CI, 1.4 to 4.4]; P < 0.001) treatment groups. More severe IRIS cases occurred in the early integrated treatment group than in the other 2 groups (35% vs. 19%; P = 0.179), and patients in the early integrated treatment group had significantly higher hospitalization rates (42% vs. 14%; P = 0.007) and longer time to resolution (70.5 vs. 29.0 days; P = 0.001) than patients in the other 2 groups. Limitations: It was not possible to assess IRIS in more patients in the sequential treatment group (n = 74) than in the late integrated (n = 50) and early integrated (n = 32) treatment groups because of loss to follow-up, withdrawal, or death within 6 months of scheduled ART initiation. This study did not assess IRIS risk in nonambulatory patients or in those with extrapulmonary and smear-negative tuberculosis. Conclusion: Initiation of ART in early stages of tuberculosis treatment resulted in significantly higher IRIS rates, longer time to resolution, and more severe cases of IRIS requiring hospitalization. These findings are particularly relevant to patients initiating ART with a CD4+ count less than 0.050 × 109 cells/L, given the increased survival benefit of early ART initiation in this group. Primary Funding Source: Comprehensive International Program of Research on AIDS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]