Search

Given the roll out of maternal antiretroviral therapy (ART) for prevention-of-perinatal-HIV-transmission, increasing numbers of children are perinatally HIV/antiretroviral exposed but uninfected (CAHEU). Some studies suggest CAHEU may be at increased risk for neurodevelopmental (ND) deficits. We aimed to assess ND performance among preschool CAHEU.This cross-sectional study assessed ND outcomes among 3-6-year-old CAHEU at entry into a multicountry cohort study.We used the Mullen Scales of Early Learning (MSEL) and Kaufman Assessment Battery for Children (KABC-II) to assess ND status among 3-6-year-old CAHEU at entry into the PROMISE Ongoing Treatment Evaluation (PROMOTE) study conducted in Uganda, Malawi, Zimbabwe and South Africa. Statistical analyses (Stata 16.1) was used to generate group means for ND composite scores and subscale scores, compared to standardized test score means. We used multivariable analysis to adjust for known developmental risk factors including maternal clinical/socioeconomic variables, child sex, growth-for-age measurements, and country.1647 children aged 3-6 years had baseline ND testing in PROMOTE; group-mean unadjusted Cognitive Composite scores on the MSEL were 85.8 (standard deviation [SD]: 18.2) and KABC-II were 79.5 (SD: 13.2). Composite score group-mean differences were noted by country, with South African and Zimbabwean children having higher scores. In KABC-II multivariable analyses, maternal age40 years, lower education, male sex, and stunting were associated with lower composite scores.Among a large cohort of 3-6 year old CAHEU from eastern/southern Africa, group-mean composite ND scores averaged within the low-normal range; with differences noted by country, maternal clinical and socioeconomic factors.

We report the long-term impact of ART in women of reproductive age (15-49 years) in Africa who have been using ART for up to 10 years. We assess outcomes of retention, adherence, maternal health, fertility intentions, and safety.This longitudinal, multicountry study (PROMOTE) enrolled women who initiated ART in an earlier perinatal clinical trial, PROMISE. PROMISE occurred from 2011 to 2016 and PROMOTE follow-up started in 2016 and is ongoing. The PROMOTE study was done at eight sites in four countries: Malawi (Blantyre and Lilongwe), South Africa (Durban and Soweto), Uganda (Kampala), and Zimbabwe (Harare, Seke North, and St Mary's). After baseline enrolment, women and their children are followed up every 6 months to collect information on medical history, antiretroviral therapy (ART) use, adherence, and health information, and to do physical examinations and laboratory tests. Obesity was defined as a body-mass index of 30 kg/mPROMOTE enrolled 1987 mothers and 2522 children. The median follow-up time for mothers was 41·8 (IQR 35·8-42·0) months and for children was 35·7 (23·8-42·0) months. Overall retention rates were 96·5% for mothers and 94·3% for children at 12 months, and, at 42 months, were 88·9% for mothers and 85·4% for children. 1115 (89·1%) of 1252 women had an undetectable viral load at 42 months, which varied by site (81·7-93·8%). Reported maternal health improved over time, with the proportion of women with excellent to very good health increasing from 67·5% at baseline to 87·5% at 42 months, the proportion of unwell participants who visited a health centre declining from 14·7% to 2·8%, and the proportion of those admitted to hospital declining from 1·5% to 1·0%. The desire to have more children was consistently high at some sites. The proportion of women with obesity was high in South Africa and increased over time from 40·2% at baseline to 52·8% at 42 months. The overall pregnancy rate was 17·6 (95% CI 16·5-18·7) per 100 women-years, and mortality rates were 2·4 (1·4-3·9) per 1000 person-years for mothers and 3·4 (2·2-5·10) per 1000 person-years for children (0-9 years).The findings from this multicountry study are reassuring. These findings show that African women can consistently use ART for a long period after initiation, and long-term benefits can be maintained. Services to support maternal HIV care, treatment, and reproductive health should be strengthened.US President's Emergency Plan for AIDS Relief.

Research suggests that women's experience of intimate partner violence (IPV) is associated with poor engagement in HIV care and treatment. However, most studies have been cross-sectional and conducted in North America. We examined the association between physical IPV and HIV care outcomes in a prospective cohort study of women living with HIV (WLHIV) in Malawi, South Africa, Uganda, and Zimbabwe. At enrollment, 15% of the 351 participants self-reported physical IPV. IPV experience was not associated with time to first engagement in HIV care or the proportion virally suppressed after 6 months on ART. Women reporting physical IPV were less likely to initiate ART within 6 months of becoming eligible (adjusted RR 0.74, 95% CI 0.53-1.03). IPV screening is critical to identify survivors and link them to appropriate services. However, addressing IPV may not increase engagement in HIV care or viral load suppression among WLHIV in sub-Saharan Africa.

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)", caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions.To centralize the accumulative knowledge on non-pharmaceutical interventions (NPIs) against COVID-19 for each country under one worldwide consortium.International COVID-19 Research Network collaborators developed a cross-sectional online-survey to assess the implications of NPIs and sanitary supply on incidence and mortality of COVID-19. Survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies and incidence and mortality were examined by multivariate regression, with log-transformed value of population as an offset value.Majority of countries/territories applied several preventive strategies including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial mask (94.6% at hospital; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to recommendation to use soap did. Deprivation of mask was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic level. Mask deprivation was pervasive regardless of economic level.NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease incidence and mortality of COVID-19. This article is protected by copyright. All rights reserved.

Background Antiretroviral therapy (ART) is associated with high rates of adverse birth outcomes, including preterm birth and low birthweight. Studies suggest that progesterone and prolactin may play important intermediary roles. Methods We analyzed data from the Antenatal Component of the PROMISE trial, a multi-center study of pregnant women taking antiretroviral regimens (lopinavir/ritonavir-containing ART or zidovudine alone) to prevent mother-to-child HIV transmission. In a nested case-control study, we compared data from women who gave birth to preterm ( Results 299 women and their newborns were included (146 cases, 153 controls). When compared to women receiving zidovudine alone, those on ART had higher odds of progesterone levels under the 10th percentile (adjusted odds ratio [AOR]:2.34, 95%CI:1.41–3.89) and 25th percentile (AOR:2.07, 95%CI:1.46–2.94). However, higher levels of progesterone—rather than lower levels—were associated with our composite case outcome at the 10th percentile (AOR:1.88, 95%CI:0.77–4.59) and 25th percentile (AOR:1.96, 95%CI:1.06–3.61). Associations were not observed between prolactin, antiretroviral regimen, and birth outcomes. Conclusion We observed lower progesterone levels among women allocated to ART regimens; however, higher progesterone levels were associated with preterm birth and/or low birthweight. While features of the study design may have contributed to these findings, they nevertheless highlight the potentially complex mechanisms underpinning adverse birth outcomes and HIV.

Malawi HIV treatment guidelines recommend same-day antiretroviral therapy (ART) initiation. Overall 97.9 % of Malawians living with HIV (PLHIV) are on ART, same-day ART initiation prevalence and factors that facilitate it have not been fully described. We assessed same-day ART initiation and described individual, health system and health facility infrastructural factors at health facilities supported by expert clients (EC). ECs are lay PLHIV who support other PLHIV. The study was conducted in urban and semi-urban primary health facilities, in Blantyre, Malawi. It was a cross-sectional, descriptive survey of PLHIV and health facility leaders. Eligibility criteria included age ≥ 18 years, new diagnosis of HIV, received counselling from ECs, and offered same day ART. The study was conducted from December 2018 to June 2021, and 321 study participants enrolled. Mean age (standard deviation) was 33 years (10) with 59% females. In total, 315 (98.1%) initiated same day ART. Four participants did not because of mental unpreparedness, one wanted to try herbal medicine and one was concerned about stigma. Participants reported health facility accessibility (99%,318/321), privacy (91%, 292/321) and quality of counselling by EC as excellent (40%,128/321). Same day ART was nearly universal. Participants’ satisfaction with health services delivery, the presence of EC, and infrastructural characteristics such as good privacy were cited as reasons favoring same day linkage to ART. The most cited reason for not starting same day ART was mental unpreparedness.

Research in rapidly evolving policy contexts can lead to the following ethical challenges for sponsors and researchers: the study’s standard of care can become different than what patients outside the study receive, there may be political or other pressure to move ahead with unproven interventions, and new findings or revised policies may decrease the relevance of ongoing studies. These ethical challenges are considerable, but not unprecedented. In this article, we review the case of a multinational, randomized, controlled perinatal HIV prevention trial, the “PROMISE” (Promoting Maternal Infant Survival Everywhere) study. PROMISE compared the relative efficacy and safety of interventions to prevent mother to child transmission of HIV. The sponsor engaged an independent international ethics panel to address controversy about the study’s standard of care and relevance as national and international guidelines changed. This ethics panel concluded that continuing the PROMISE trial as designed was ethically permissible because: (1) participants in all arms received interventions that were effective, and there was insufficient evidence about whether one intervention was more effective or safer than the other, and (2) data from PROMISE could be useful for a diverse range of stakeholders. In general, trials designed to inform rapidly evolving policy issues should develop mechanisms to revisit social value while recognizing that the value of research varies for diverse stakeholders with legitimate reasons to weigh evidence differently. We conclude by providing four reasons that trials may depart from the standard of care after a change in policy, while remaining ethically justifiable, and by suggesting how to improve existing trial oversight mechanisms to address evolving social value.

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.

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.

Background Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. Methods The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. Results Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7–36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4–34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. Conclusions Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.

Background: About 90% of unintended pregnancies are attributed to non-use of effective contraception – tubal ligation, or reversible effective contraception (REC) including injectables, oral pills, intra-uterine device (IUD), and implant. We assessed prevalence of unintended pregnancy and factors associated with using RECs, and Long-Acting-Reversible-Contraceptives (LARCs) – implants and IUDs, among women living with HIV (WLHIV) on antiretroviral therapy (ART).Methods: Cross-sectional analysis of US-PEPFAR PROMOTE cohort enrollment (December 2016 to June 2017) data, from Malawi, South Africa, Uganda, and Zimbabwe. Wilcoxon Rank Sum and Fisher’s exact tests were used to compare continuous and categorical variables. Separate outcome (REC and LARC) modified-Poisson regression models were used to estimate prevalence risk ratio (PRR) and corresponding 95% confidence interval (CI). Results: Of 1,987 enrolled WLHIV, 990 (49.8%) reported their last/current pregnancy was unintended; 1,027/1,254 (81.9%) non-pregnant women with child-bearing potential reported current use of effective contraception including 215/1,254 (17.1%) LARC users. Compared to Zimbabwe, REC rates were similar in South Africa, aPRR=0.97 (95% CI: 0.90-1.04), p=0.355, lower in Malawi, aPRR = 0.84 (95% CI: 0.78-0.91), pConclusions: We observed high rates of unintended pregnancy and considerable gaps in use of effective contraceptives particularly LARCs. Integrated HIV and reproductive health country-level efforts to improve effective contraceptive utilization should consider HIV load, and social factors regarding education, sexual activity, sexual partnerships, fertility desires, and economic independence.

OBJECTIVE: To determine time from delivery to resumption of sexual activity and menses among HIV-infected women on antiretroviral treatment (ART) and HIV-uninfected women. METHODS: HIV-infected women on ART and HIV-uninfected women were recruited from five health facilities at delivery and followed prospectively for a maximum of 1 year in Blantyre, Malawi from January 2016 to September 2017. Sociodemographic, clinical, and laboratory data were collected at delivery and 1.5, 3, 6, 9, and 12 months. Descriptive, time to event Kaplan–Meier, and multivariable Cox proportional hazards analyses were conducted. RESULTS: Data on 878 women (460 [52.4%] HIV-uninfected and 418 [47.6%] HIV-infected, P=0.156) who attended at least one follow-up visit were analyzed. Among HIV-uninfected compared to HIV-infected women, respectively, the median number of days to resumption of sexual activity was 180 vs 181; to irregular menses was 82 vs 71; and to regular menses was 245 vs 366. In multivariable models, being married was associated with early resumption of sexual activity (hazard ratio [HR] 1.91, P

HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa and vertical transmission rates remain high despite established strategies for HIV prevention. During the MTN-041/MAMMA study, we explored the influence of grandmothers (mothers and mothers-in-law of pregnant and breastfeeding women) in eastern and southern Africa on the health-related decisions of pregnant and breastfeeding women and their potential to support use of HIV prevention products. To do this we used structured questionnaires and focus group discussions with three stakeholder groups: 1) grandmothers, 2) HIV-uninfected currently or recently pregnant or breastfeeding women and 3) male partners of currently or recently pregnant or breastfeeding women. A total of 23 focus group discussions comprising 68 grandmothers, 65 pregnant or breastfeeding women and 63 male partners were completed across four study sites. Grandmothers were described as important sources of information during pregnancy and breastfeeding playing both supportive and influencer roles due to personal maternal experience and generational knowledge. While pregnant and breastfeeding women were not keen to involve grandmothers in HIV prevention decision making, they were accepting of grandmothers’ involvement in a supportive role. Grandmothers expressed willingness to support pre-exposure prophylaxis use and agreed with the other two stakeholder groups that this decision should be made by women themselves or together with partners. These novel data indicate potential for grandmothers’ health related supportive roles to be extended to support decision-making and adherence to biomedical HIV prevention options, and possibly contribute to the decline in HIV acquisition among pregnant and breastfeeding women in these communities.

Background: HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa (SSA) and vertical transmission rates remain high despite established strategies for HIV prevention. Methods: We explored grandmothers’ (mothers/mothers-in-law) influence on pregnant and breastfeeding women’s health-related decisions and their potential to support use of HIV prevention products utilizing qualitative data collected from grandmothers, HIV-uninfected, currently/recently pregnant or breastfeeding women and male partners of currently/recently pregnant or breastfeeding women during the MTN-041/MAMMA study. Results: Grandmothers were described as important sources of information, playing both supportive and influencer roles, due to personal maternal experience and generational knowledge. Grandmothers expressed willingness to support pre-exposure prophylaxis (PrEP) use and agreed with other groups that this decision should be made by women themselves and/or with partners. Conclusion: With the right framing and approach, grandmothers’ supportive roles can optimise uptake and adherence to biomedical HIV prevention and reduce HIV acquisition among pregnant and breastfeeding women in these communities.

Background: Recent studies show that ART is associated with an adverse birth outcome in HIV-infected women.Aim: To compare rates of low birthweight (LBW) and preterm birth (PTB) between HIV-infecte...

Objectives We set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV. Design IMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858). Methods IMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir–maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented. Results Among 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value Conclusions Bone mineral density decline through week 74 postpartum was greater among breastfeeding HIV-infected women randomized to receive maternal TDF-ART during breastfeeding compared to those mothers whose infants received nevirapine prophylaxis.

Introduction Men who have sex with men (MSM) and transgender women (TGW) in sub‐Saharan Africa (SSA) are profoundly affected by HIV with high HIV prevalence and incidence. This population also faces strong social stigma and legal barriers, potentially impeding participation in research. To date, few multi‐country longitudinal HIV research studies with MSM/TGW have been conducted in SSA. Primary objective of the HIV Prevention Trials Network (HPTN) 075 study was to assess feasibility of recruiting and retaining a multinational prospective cohort of MSM/TGW in SSA for HIV prevention research. Methods HPTN 075, conducted from 2015 to 2017, was designed to enroll 400 MSM/TGW at four sites in SSA (100 per site: Kisumu, Kenya; Blantyre, Malawi; Cape Town, South Africa; and Soweto, South Africa). The number of HIV‐positive persons was capped at 20 per site; HIV‐positive persons already in care were excluded from participation. The one‐year study included five biobehavioural assessments. Community‐based input and risk mitigation protocols were included in study design and conduct. Results Of 624 persons screened, 401 were enrolled. One in five participants was classified as transgender. Main reasons for ineligibility included: (a) being HIV positive after the cap was reached (29.6%); (b) not reporting anal intercourse with a man in the preceding three months (20.6%); and (c) being HIV positive and already in care (17.5%). Five (1.2%) participants died during the study (unrelated to study participation). 92.9% of the eligible participants (368/396) completed the final study visit and 86.1% participated in all visits. The main, overlapping reasons for early termination included being (a) unable to adhere to the visit schedule, predominantly because of relocation (46.4%), and (b) unable to contact the participant (32.1%). Participants reported strong motivation to participate and few participation barriers. Four participants reported social harms (loss of confidentiality and sexual harassment by study staff) that were successfully addressed. Conclusions HPTN 075 successfully enrolled a multinational sample of MSM/TGW in SSA in a prospective HIV prevention research study with a high retention rate and few documented social harms. This supports the feasibility of conducting large‐scale research trials in this population to address its urgent, unmet HIV prevention needs.

BACKGROUND. Adverse pregnancy outcomes such as preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) remain major global problems. We compared pregnancy outcomes among HIV-infected women receiving antiretroviral treatment (ART) and with CD4 ≥350 cells, and HIV-uninfected women to assess if disparities associated with HIV infection have been eliminated through use of ART. SETTING: Observational study conducted at five health facilities in Blantyre, Malawi during 2016–2017. METHODS. HIV-infected women receiving the national ART regimen (efavirenz+lamuvidine+tenfovir) and HIV-uninfected women were consented and enrolled at delivery. Data collected included sociodemographic and clinical; gestational age (GA); birth weight (BW); infant/maternal anthropometry; and laboratory results. We defined PTB as GA0·05). Of 231 SGA infants, 78·8% were proportionate and 21% were disproportionate. Of the 614 HIV-infected women on ART, 75% had undetectable virus at delivery. CONCLUSION. ART use has reduced the high rates of adverse pregnancy outcomes among HIV-infected women. However, the rates remain high irrespective of HIV infection and require appropriate interventions.

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.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.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; p0·0001). 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.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.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.

Hypertension is the leading risk factor for global disease burden. Self-management of high blood pressure (BP) through self-monitoring and self-titration of medications, has proved to be one successful and cost-effective tool to achieve better BP control in many high-income countries but not much is known about its potential in low- and middle-income countries (LMICs). We used semi-structured questionnaires and focus groups in three LMICs; Peru, Cameroon and Malawi to examine perceptions and attitudes of patients diagnosed with essential hypertension towards living with hypertension, BP measurement and treatment, patient–physician relationship and opinions about self-management of high blood pressure. Results in all three countries were comparable. Patients showed varied levels of health literacy related to hypertension. BP measurement habits were mostly affected by resources available and caregiver support. Treatment and adherence to it were primarily affected by cost. Most patients were welcoming of the idea of self-management but skeptical about the ability to do self-monitoring accurately and the safety involving self-titration of medications.

Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

This study examined HIV superinfection in HIV-infected women postpartum, and its association with mother-to-child transmission (MTCT).Plasma samples were obtained from HIV-infected women who transmitted HIV to their infants after 6 weeks of age (transmitters, n = 91) and HIV-infected women who did not transmit HIV to their infants (nontransmitters, n = 91). These women were originally enrolled in a randomized trial for prevention of MTCT of HIV in Malawi (Post-Exposure Prophylaxis of Infants trial in Malawi).Two HIV genomic regions (p24 and gp41) were analyzed by next-generation sequencing for HIV superinfection. HIV superinfection was established if the follow-up sample contained a new, phylogenetically distinct viral population. HIV superinfection and transmission risk were examined by multiple logistic regression, adjusted for Post-Exposure Prophylaxis of Infants study arm, baseline viral load, baseline CD4 cell count, time to resumption of sex, and breastfeeding duration.Transmitters had lower baseline CD4 cell counts (P = 0.001) and higher viral loads (P 0.0001) compared with nontransmitters. There were five cases of superinfection among transmitters (rate of superinfection = 4.7/100 person-years) compared with five cases among the nontransmitters (rate of superinfection = 4.4/100 person-years; P = 0.78). HIV superinfection was not associated with increased risk of postnatal MTCT of HIV after controlling for maternal age, baseline viral load, and CD4 cell count (adjusted odds ratio = 2.32, P = 0.30). Longer breastfeeding duration was independently associated with a lower risk of HIV superinfection after controlling for study arm and baseline viral load (P = 0.05).There was a significant level of HIV superinfection in women postpartum, but this was not associated with an increased risk of MTCT via breastfeeding.

Previous surveys of men who have sex with men (MSM) in Africa have not adequately profiled HIV status and risk factors by sex work status. MSM in Nairobi, Kenya, were recruited using respondent-driven sampling, completed a behavioral interview, and were tested for HIV and sexually transmitted infections. Overlapping recruitment among 273 male sex workers and 290 other MSM was common. Sex workers were more likely to report receptive anal sex with multiple partners (65.7% versus 18.0%, P < 0.001) and unprotected receptive anal intercourse (40.0% versus 22.8%, P = 0.005). Male sex workers were also more likely to be HIV infected (26.3% versus 12.2%, P = 0.007).

We conducted a respondent driven sampling survey to estimate HIV prevalence and risk behavior among female sex workers (FSWs) in Nairobi, Kenya. Women aged 18 years and older who reported selling sex to a man at least once in the past 3 months were eligible to participate. Consenting FSWs completed a behavioral questionnaire and were tested for HIV and sexually transmitted infections (STIs). Adjusted population-based prevalence and 95 % confidence intervals (CI) were estimated using RDS analysis tool. Factors significantly associated with HIV infection were assessed using log-binomial regression analysis. A total of 596 eligible participants were included in the analysis. Overall HIV prevalence was 29.5 % (95 % CI 24.7-34.9). Median age was 30 years (IQR 25-38 years); median duration of sex work was 12 years (IQR 8-17 years). The most frequent client-seeking venues were bars (76.6 %) and roadsides (29.3 %). The median number of clients per week was seven (IQR 4-18 clients). HIV testing was high with 86.6 % reported ever been tested for HIV and, of these, 63.1 % testing within the past 12 months. Of all women, 59.7 % perceived themselves at 'great risk' for HIV infection. Of HIV-positive women, 51.0 % were aware of their infection. In multivariable analysis, increasing age, inconsistent condom use with paying clients, and use of a male condom as a method of contraception were independently associated with unrecognized HIV infection. Prevalence among STIs was low, ranging from 0.9 % for syphilis, 1.1 % for gonorrhea, and 3.1 % for Chlamydia. The data suggest high prevalence of HIV among FSWs in Nairobi. Targeted and routine HIV and STI combination prevention strategies need to be scaled up or established to meet the needs of this population.

Population-based surveys with HIV testing in settings with low testing coverage provide opportunities for participants to learn their HIV status. Survey participants (15-64 years) in a 2007 nationally representative population-based HIV serologic survey in Kenya received a voucher to collect HIV test results at health facilities 6 weeks after blood draw. Logistic regression models were fitted to identify predictors of individual and couple collection of results. Of 15,853 adults consenting to blood draw, 7,222 (46.7%) collected HIV test results (46.5% men, 46.8% women). A third (39.5%) of HIV-infected adults who were unaware of their infection and 48.2% of those who had never been tested learned their HIV status during KAIS. Individual collection of HIV results was associated with older age, with the highest odds among adults aged 60-64 years (adjusted odds ratio [AOR], 1.6, 95% confidence interval [CI] 1.2-2.1); rural residence (AOR 1.8, 95%CI 1.2-2.6); and residence outside Nairobi, with the highest odds in the sparsely populated North Eastern province (AOR 8.0, 95%CI 2.9-21.8). Of 2,685 married/cohabiting couples, 18.5% collected results as a couple. Couples in Eastern province and in the second and middle wealth quintiles were more likely to collect results than those in Nairobi (AOR 3.2, 95%CI 1.1-9.4) and the lowest wealth quintile (second AOR 1.5, 95%CI 1.1-2.3; middle AOR 1.6, 95% CI 1.2-2.3, respectively. Many participants including those living with HIV learned their HIV status in KAIS. Future surveys need to address low uptake of results among youth, urban residents, couples and those with undiagnosed HIV infection.

Background: Control of hypertension in low- and middle-income countries (LMICs) is poor, often less than 10%. A strong body of evidence demonstrates that home blood pressure management lowers blood pressure, and recent guidelines from the National Institute for Clinical Health and Excellence recommends home blood pressure monitoring. However, the preponderance of data on the benefits of home blood pressure management comes from studies in high-income countries. Objective: The objective of the study is to examine whether an intervention of home blood pressure management is feasible in LMICs. Home blood pressure management is defined as self-monitoring of blood pressure and self-titration of antihypertensive medications. We will identify barriers and facilitators of home blood pressure management and explore unique contextual factors in LMICs that influence implementation of home blood pressure management. Methods: Participants will be recruited from 6 sites from 2015 to 2018. Patients and health care workers will be included. We will use mixed methods including focus groups, interviews, and standardized checklists. When possible, we will adapt materials from prior successful studies so that they are culturally and contextually appropriate. Results: This ongoing study is funded by the World Heart Federation. The information that is obtained will be used to develop a randomized clinical trial of home blood pressure management in LMICs. Conclusions: The data generated from this qualitative study will provide much needed information from patients and health care workers about barriers and facilitators of home blood pressure management and unique contextual factors that might influence implementation of home blood pressure management in LMICs. [JMIR Res Protoc 2017;6(10):e188]

INTRODUCTION: Continuous evaluation of child survival is needed in sub-Saharan Africa where HIV prevalence among women of reproductive age continues to be high. We examined mortality levels and trends over a period of approximately 20 years among HIV-unexposed and -exposed children in Blantyre Malawi. METHODS: Data from 5 prospective cohort studies conducted at a single research site from 1989 to 2009 were analyzed. In these studies children born to HIV-infected and -uninfected mothers were enrolled at birth and followed longitudinally for at least 2 years. Information on sociodemographic HIV infection status survival and associated risk factors was collected in all studies. Mortality rates were estimated using birth-cohort analyses stratified by maternal and infant HIV status. Multivariate Cox regression models were used to determine risk factors associated with mortality. RESULTS: The analysis included 8286 children. From 1989 to 1995 overall mortality rates (per 100 person-years) in these clinic-based cohorts remained comparable among HIV-uninfected children born to HIV-uninfected mothers (range 3.3-6.9) or to HIV-infected mothers (range 2.5-7.5). From 1989 to 2009 overall mortality remained high among all children born to HIV-infected mothers (range 6.3-19.3) and among children who themselves became infected (range 15.6-57.4 1994-2009). Only lower birth weight was consistently and significantly (P < 0.05) associated with higher child mortality. CONCLUSIONS: HIV infection among mothers and children contributed to high levels of child mortality in the African setting in the pretreatment era. In addition to services that prevent mother-to-child transmission of HIV other programs are needed to improve child survival by lowering HIV-unrelated mortality through innovative interventions that strengthen health infrastructure.

Abstract 33 Background: Enabled by collaboration and political stability, Malawi is a global leader for HIV research and implementation. We undertook this work to identify ways to leverage successes in HIV treatment and research for cancer and noncommunicable diseases (NCDs). Methods: Over more than two decades, investment from the National Institutes of Health (NIH) and other funders has allowed Malawi participation in international HIV networks. As these sought to address HIV-positive cancer, investment occurred to increase pathology, improve cancer registration, scale up cervical cancer screening, and improve nursing and pharmacy skills for chemotherapy administration. This allowed Malawi to participate in multinational clinical trials for HIV-positive Kaposi sarcoma treatment and cervical cancer prevention. Building on this, Malawi was one of six countries in 2014 to receive an NIH U54 consortium award for HIV-positive malignancies and was one of six countries added to the National Cancer Institute (NCI) AIDS Malignancy Consortium. In 2016, expanding beyond HIV-positive cancer, Malawi was one of three countries invited to join a new NCI–International Agency for Research on Cancer esophageal cancer consortium, one of five recipients of a new NCI Burkitt lymphoma award, and one of six recipients of a new NCI P20 grant for a regional center of research excellence for NCDs. Malawi is also one of 11 countries to convene a Lancet noncommunicable diseases and injury poverty commission for NCDs and injury. Finally, partners have improved surveillance and treatment for hypertension, diabetes, injury, and sickle cell anemia, in part, through a national Knowledge Translation Platform for HIV-NCD integration. With this support and funding, career development opportunities are embedded for Malawian NCD researchers. Results: Building on successes in HIV treatment and research, Malawi has become a global leader for cancer and NCD research and implementation. Conclusion: Continue developing a multilateral national platform for NCD research and implementation that is globally impactful and can lead to measurable outputs for individual cancer and NCD focus areas. Funding: National Institutes of Health. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

Objective: To identify factors associated with prevalent HIV in a national HIV survey in Kenya. Methods: The Kenya AIDS Indicator Survey was a nationally representative population-based sero-survey that examined demographic and behavioral factors and serologic testing for HIV, HSV-2 and syphilis in adults aged 15-64 years. We analyzed questionnaire and blood testing data to identify significant correlates of HIV infection among sexually active adults. Results: Of 10,957 eligible women and 8,883 men, we interviewed 10,239 (93%) women and 7,731 (87%) men. We collected blood specimens from 9,049 women and 6,804 men of which 6,447 women and 5,112 men were sexually active during the 12 months prior to the survey. HIV prevalence among sexually active adults was 7.4%. Factors independently associated with HIV among women were region (Nyanza vs Nairobi: adjusted OR [AOR] 1.6, 95%CI 1.1-2.3), number of lifetime sex partners (6-9 vs 0-1 partners: AOR 3.0, 95%CI 1.6-5.9), HSV-2 (AOR 6.5, 95%CI 4.9-8.8), marital status (widowed vs never married: AOR 2.7, 95%CI 1.5-4.8) and consistent condom use with last sex partner (AOR 2.3, 95%CI 1.6-3.4). Among men, correlates of HIV infection were 30-to-39-year-old age group (AOR 5.2, 95%CI 2.6-10.5), number of lifetime sex partners (10+ vs 0-1 partners, AOR 3.5, 95%CI 1.4-9.0), HSV-2 (AOR 4.7, 95%CI 3.2-6.8), syphilis (AOR 2.4, 95%CI 1.4-4.0), consistent condom use with last sex partner (AOR 2.1, 95% CI 1.5-3.1) and lack of circumcision (AOR 4.0, 95%CI 2.8 - 5.5). Conclusion: Kenya’s heterogeneous epidemic will require regional and gender-specific prevention approaches.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a known biologic cofactor for human immunodeficiency virus (HIV) transmission and acquisition. The Kenya AIDS Indicator Survey 2007 provided Kenyas first nationally representative estimate of HSV-2 prevalence and risk factors. METHODS: KAIS was a household serosurvey among women and men aged 15 to 64 years. The survey included a behavioral interview and serum testing for HSV-2 HIV and syphilis infections. Results were weighted for sampling design and nonresponse. RESULTS: Of 19840 eligible individuals 90% completed an interview and 80% consented to testing. In all 35% were infected with HSV-2 of which 42% were women and 26% were men. Between 15 and 24 years of age HSV-2 prevalence increased from 7% to 34% in women and 3% to 14% in men. Among couples 30% were HSV-2 concordant-positive 21% were discordant and 49% were concordant-negative. In all 81% of HIV-infected persons were coinfected with HSV-2. HIV prevalence was 16% among those with HSV-2 and 2% among those without HSV-2. Women with circumcised partners had an HSV-2 prevalence of 39% compared to 77% of women with uncircumcised partners. CONCLUSIONS: One-third of Kenyans were HSV-2 infected. HIV-1 infection age female sex and lack of male circumcision were population-level predictors for HSV-2 infection. Targeted prevention interventions are needed including an effective vaccine.

Background Respondent-driven sampling (RDS) is used in a variety of settings to study hard-to-reach populations at risk for HIV and sexually transmitted infections. However, practices leading to successful recruitment among diverse populations in low-resource settings are seldom reported. We implemented the first, integrated, bio-behavioural surveillance survey among men who have sex with men, female sex workers and people who injected drugs in Nairobi, Kenya. Methods The survey period was June 2010 to March 2011, with a target sample size of 600 participants per key populations. Formative research was initially conducted to assess feasibility of the survey. Weekly monitoring reports of respondent characteristics and recruitment chain graphs from NetDraw illustrated patterns and helped to fill recruitment gaps. Results RDS worked well with men who have sex with men and female sex workers with recruitment initiating at a desirable pace that was maintained throughout the survey. Networks of people who injected drugs were well-integrated, but recruitment was slower than the men who have sex with men and female sex workers surveys. Conclusion By closely monitoring RDS implementation and conducting formative research, RDS studies can effectively develop and adapt strategies to improve recruitment and improve adherence to the underlying RDS theory and assumptions.

Objectives The authors used data from the Kenya AIDS Indicator Survey (KAIS) 2007 to determine the prevalence of syphilis and associated risk factors among adults aged 15–64 years. Methods KAIS was a nationally representative population-based sero-survey that examined demographic and behavioural indicators and serological testing for syphilis, HIV and herpes simplex virus type 2 (HSV-2) in adults aged 15–64 years. The authors analysed data from 8935 women and 6727 men with complete syphilis results. Logistic regression models stratified by sex were used to assess potential factors associated with syphilis sero-prevalence. Results Overall, 262 adults tested positive for syphilis (1.8%, 95% CI 1.5% to 2.1%); sero-prevalence was similar among women and men (1.7%, 95% CI 1.3% to 2.0% and 1.9%, 95% CI 1.5% to 2.3%, respectively). Syphilis prevalence was the highest among men with HIV (6.4%, 95% CI 3.1% to 9.7%) and HSV-2 (4.5%, 95% CI 3.4% to 5.7%) infection. Independent risk factors for syphilis included HIV (men only, adjusted OR (AOR) 3.4, 95% CI 1.6% to 7.1%), HSV-2 (women, AOR 3.5, 95% CI 2.1% to 5.8%; men AOR 2.2, 95% CI 1.3% to 3.7%), lack of male circumcision (AOR 2.2, 95% CI 1.3% to 3.7%), poorest or poorer versus richest wealth index (women, AOR 2.0, 95% CI 1.0% to 4.2%; men AOR 2.5, 95% CI 1.4% to 4.9%) and no primary versus secondary or more education in men (AOR 4.8, 95% CI 2.0% to 11.7%). Conclusions Syphilis prevalence in the general population in Kenya is relatively low and eradication could be possible but would require intensified syphilis prevention and control efforts, including routine screening in HIV, sexually transmitted infection and antenatal care clinics as well as in family planning and male circumcision settings.