Introduction
HIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. ...The World Health Organization recommends offering pre‐exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.
Methods
We used a standard Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)‐based oral PrEP safety in pregnant and breastfeeding HIV‐uninfected women.
Results and discussion
We identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP‐exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV‐uninfected women who use PrEP during pregnancy and/or lactation.
Conclusions
Expanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.
We estimated the effects of HIV stigma on mental health and treatment outcomes for youth with HIV (YWH).
Secondary analysis of data for YWH ages 15-24 years in Western Kenya.
Participants completed a ...longitudinal survey (baseline, months 6 and 12) assessing socio-demographics, antiretroviral therapy (ART) adherence, depressive symptoms (PHQ-9), and HIV stigma (10-item Wright scale). First viral load (VL) after enrollment was abstracted from records. We estimated risk of depressive symptoms (score > 4), nonadherence (missing ≥2 days of ART in a month), and detectable VL (≥50 copies/ml) for each standard deviation (SD) increase in HIV stigma score, adjusted for age and sex (and regimen in VL model). The generalizing estimating equation models included measures for the three visits.
Median age for the 1011 YWH was 18 years. At baseline, frequency of nonadherence, depressive symptoms and detectable VL was 21%, 21%, and 46%, respectively. Mean stigma score was 25 (SD = 7.0). Each SD stigma score increment was associated with higher risk of depressive symptoms {adjusted relative risk aRR 1.31 95% confidence interval (CI): 1.20-1.44}, nonadherence aRR 1.16 (CI: 1.05-1.27) and detectable VL aRR 1.20 (CI: 1.08-1.32). Experienced and anticipated stigma were associated with detectable VL aRR 1.16 (CI: 1.10-1.22) and aRR 1.23 (CI: 1.12-1.35), respectively. Internalized and perceived community stigma were associated with depressive symptoms aRR 1.31 (CI: 1.21-1.40) and aRR 1.24 (CI: 1.13-1.36), respectively.
Stigma was associated with depressive symptoms, nonadherence and detectable VL. Interventions to decrease stigma may improve virologic and mental health outcomes in YWH.
Disruptions of vaginal microbiota might increase women's susceptibility to HIV infection. Advances in molecular microbiology have enabled detailed examination of associations between vaginal bacteria ...and HIV acquisition. Therefore, this study aimed to evaluate the association between the concentrations of specific vaginal bacteria and increased risk of HIV acquisition in African women.
We did a nested case-control study of participants from eastern and southern Africa. Data from five cohorts of African women (female sex workers, pregnant and post-partum women, and women in serodiscordant relationships) were used to form a nested case-control analysis between women who acquired HIV infection versus those who remained seronegative. Deep sequence analysis of broad-range 16S rRNA gene PCR products was applied to a subset of 55 cases and 55 controls. From these data, 20 taxa were selected for bacterium-specific real-time PCR assays, which were examined in the full cohort as a four-category exposure (undetectable, first tertile, second tertile, and third tertile of concentrations). Conditional logistic regression was used to generate odds ratios (ORs) and 95% CIs. Regression models were stratified by cohort, and adjusted ORs (aORs) were generated from a multivariable model controlling for confounding variables. The Shannon Diversity Index was used to measure bacterial diversity. The primary analyses were the associations between bacterial concentrations and risk of HIV acquisition.
Between November, 2004, and August, 2014, we identified 87 women who acquired HIV infection (cases) and 262 controls who did not acquire HIV infection. Vaginal bacterial community diversity was higher in women who acquired HIV infection (median 1·3, IQR 0·4–2·3) than in seronegative controls (0·7, 0·1–1·5; p=0·03). Seven of the 20 taxa showed significant concentration-dependent associations with increased odds of HIV acquisition: Parvimonas species type 1 (first tertile aOR 1·67, 95% CI 0·61–4·57; second tertile 3·01, 1·13–7·99; third tertile 4·64, 1·73–12·46; p=0·005) and type 2 (first tertile 3·52, 1·63–7·61; second tertile 0·85, 0·36–2·02; third tertile 2·18, 1·01–4·72; p=0·004), Gemella asaccharolytica (first tertile 2·09, 1·01–4·36; second tertile 2·02, 0·98–4·17; third tertile 3·03, 1·46–6·30; p=0·010), Mycoplasma hominis (first tertile 1·46, 0·69–3·11; second tertile 1·40, 0·66–2·98; third tertile 2·76, 1·36–5·63; p=0·048), Leptotrichia/Sneathia (first tertile 2·04, 1·02–4·10; second tertile 1·45, 0·70–3·00; third tertile 2·59, 1·26–5·34; p=0·046), Eggerthella species type 1 (first tertile 1·79, 0·88–3·64; second tertile 2·62, 1·31–5·22; third tertile 1·53, 0·72–3·28; p=0·041), and vaginal Megasphaera species (first tertile 3·15, 1·45–6·81; second tertile 1·43, 0·65–3·14; third tertile 1·32, 0·57–3·05; p=0·038).
Differences in the vaginal microbial diversity and concentrations of key bacteria were associated with greater risk of HIV acquisition in women. Defining vaginal bacterial taxa associated with HIV risk could point to mechanisms that influence HIV susceptibility and provide important targets for future prevention research.
National Institute of Child Health and Human Development.
Introduction
Lack of viral suppression (VS) among pregnant and breastfeeding women living with HIV poses challenges for maternal and infant health, and viral load (VL) monitoring via centralized ...laboratory systems faces many barriers. We aimed to determine the impact of point‐of‐care (POC) VL and targeted drug resistance mutation (DRM) testing in improving VS among pregnant and postpartum women on antiretroviral therapy.
Methods
We conducted a pre/post‐intervention prospective cohort study among 820 pregnant women accessing HIV care at five public‐sector facilities in western Kenya from 2019 to 2022. The pre‐intervention or “control” group consisted of standard‐of‐care (SOC) centralized VL testing every 6 months and the post‐intervention or “intervention” group consisted of a combined strategy of POC VL every 3 months, targeted DRM testing, and clinical management support. The primary outcome was VS (VL ≤1000 copies/ml) at 6 months postpartum; secondary outcomes included uptake and turnaround times for VL testing and sustained VS.
Results
At 6 months postpartum, 321/328 (98%) of participants in the intervention group and 339/347 (98%) in the control group achieved VS (aRR 1.00, 95% confidence interval CI 0.98, 1.02). When assessing VS using a threshold of <40 copies/ml, VS proportions were lower overall (90−91%) but remained similar between groups. Among women with viraemia (VL>1000 copies/ml) who underwent successful DRM testing in the intervention group, all (46/46, 100%) had some DRMs and 20 (43%) had major DRMs (of which 80% were nucleos(t)ide reverse transcriptase inhibitor mutations). POC VL testing uptake was high (>89%) throughout pregnancy, delivery, and postpartum periods, with a median turnaround time of 1 day (IQR 1, 4) for POC VL in the intervention group and 7 days (IQR 5, 9) for SOC VL in the control group. Sustained VS throughout follow‐up was similar between groups with either POC or SOC VL testing (90−91% for <1000 copies/ml, 62–70% for <40 copies/ml).
Conclusions
Our combined strategy markedly decreased turnaround time but did not increase VS rates, which were already very high, or sustained VS among pregnant and postpartum women living with HIV. Further research on how best to utilize POC VL and DRM testing is needed to optimize sustained VS among this population.
Abstract
Background
Task shifting is a well-tested implementation strategy within low- and middle-income countries that addresses the shortage of trained mental health personnel. Task shifting can ...increase access to care for patients with mental illnesses. In Kenya, community health workers (CHWs) are a combination of community health assistants and community health volunteers and have played a crucial role on this front. In our study, we seek to assess the acceptability and feasibility of Group Interpersonal Psychotherapy (IPT-G) delivered by CHWs among depressed postpartum adolescents (PPAs) living with human immunodeficiency virus (HIV).
Method
The study used theoretical framework of behaviour change including: Capability, Opportunity and Motivation (COM-B model) to help understand behavioural changes due to IPT-G intervention delivered by the CHWs. 24 PPAs were administered IPT-G by trained CHWs from two health centres. A two-arm study design (IPT-G intervention and treatment as usual) with an intent to treat was used to assess the acceptability and feasibility of IPT-G. With purposeful sampling, participants who scored > 10 on the Edinburgh postnatal depression scale and who were 6–12 weeks postpartum were eligible for the study. Participants were equally distributed into two groups: one group for intervention and another as a wait-listed group. This was achieved by randomly allocating numerical numbers and separating those with odd numbers (intervention group) and even numbers (wait-listed group). Focus group discussions and in-depth interviews ascertained the experiences and perceptions of the PPAs and the CHWs during IP-G delivery process. In addition to weekly face-to-face continuous supportive supervision for the CHWs, the researchers also utilized phone calls, short messages services and WhatsApp instant messaging services.
Results
The CHWs found the intervention useful for their own knowledge and skill-set. With regards to participation, 21 out of the 24 adolescents attended all sessions. Most of the adolescents reported an improvement in their interpersonal relationships with reduced distress and lessening of HIV-related stigma. Primary healthcare workers embraced the intervention by accommodating the sessions in their routine clinic activities.
Conclusion
Our study demonstrates the possible benefits of task shifting in addressing mental health problems within low-resource settings in Kenya, and IPT-G is demonstrated to be both acceptable and feasible by health workers and adolescents receiving care.
Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial ...constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting.
A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviral-naïve individuals initiating free highly active antiretroviral therapy (HAART) in the form of fixed-dose combination pills (d4T, 3TC, and nevirapine) were randomized to one of four arms: counseling (three counseling sessions around HAART initiation), alarm (pocket electronic pill reminder carried for 6 months), counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence <80% (hazard ratio HR = 0.71; 95% confidence interval CI 0.49-1.01; p = 0.055) and 59% less likely to experience viral failure (HIV-1 RNA ≥5,000 copies/ml) (HR 0.41; 95% CI 0.21-0.81; p = 0.01) compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence (HR 0.93; 95% CI 0.65-1.32; p = 0.7) or viral failure (HR 0.99; 95% CI 0.53-1.84; p = 1.0) compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution.
Intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure during 18-month follow-up, while use of an alarm device had no effect. As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV.
Despite increased treatment availability, HIV-infected individuals continue to start antiretroviral therapy (ART) late in disease progression, increasing early mortality risk.
Nested prospective ...cohort study within a randomized clinical trial of adult patients initiating ART at clinics in urban Nairobi and rural Maseno, Kenya, between 2013-2014. We estimated mortality incidence rates following ART initiation and used Cox proportional hazards regression to identify predictors of mortality within 12 months of ART initiation. Analyses were stratified by clinic site to examine differences in mortality correlates and risk by location.
Among 811 participants initiated on ART, the mortality incidence rate within a year of initiating ART was 7.44 per 100 person-years (95% CI 5.71, 9.69). Among 207 Maseno and 612 Nairobi participants initiated on ART, the mortality incidence rates (per 100 person-years) were 12.78 (95% CI 8.49, 19.23) and 5.72 (95% CI 4.05, 8.09). Maseno had a 2.20-fold greater risk of mortality than Nairobi (95% CI 1.29, 3.76; P = 0.004). This association remained adjusted hazard ratio (HR) = 2.09 (95% CI 1.17, 3.74); P = 0.013 when adjusting for age, gender, education, pre-treatment drug resistance (PDR), and CD4 count, but not when adjusting for BMI. In unadjusted analyses, other predictors (P<0.05) of mortality included male gender (HR = 1.74), age (HR = 1.04 for 1-year increase), fewer years of education (HR = 0.92 for 1-year increase), unemployment (HR = 1.89), low body mass index (BMI<18.5 m/kg2; HR = 4.99), CD4 count <100 (HR = 11.67) and 100-199 (HR = 3.40) vs. 200-350 cells/μL, and pre-treatment drug resistance (PDR; HR = 2.49). The increased mortality risk associated with older age, males, and greater education remained when adjusted for location, age, education and PDR, but not when adjusted for BMI and CD4 count. PDR remained associated with increased mortality risk when adjusted for location, age, gender, education, and BMI, but not when adjusted for CD4 count. CD4 and BMI associations with increased mortality risk persisted in multivariable analyses. Despite similar baseline CD4 counts across locations, mortality risk associated with low CD4 count, low BMI, and PDR was greater in Maseno than Nairobi in stratified analyses.
High short-term post-ART mortality was observed, partially due to low CD4 count and BMI at presentation, especially in the rural setting. Male gender, older age, and markers of lower socioeconomic status were also associated with greater mortality risk. Engaging patients earlier in HIV infection remains critical. PDR may influence short-term mortality and further studies to optimize management will be important in settings with increasing PDR.
Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear.
Children were recruited from hospital and health centers providing HIV ...care and treatment in Nairobi, Kenya.
Cognitive, behavioral, and motor outcomes were assessed in children with HIV and early ART (<1 year), children with HIV and late ART (1.5-6 years), and children HIV-unexposed uninfected (CHUU). Domain z scores and odds neurobehavioral impairment (≤15th percentile in CHUU) were compared in adjusted analyses.
Children with HIV initiated ART at median ages 0.4 (early ART) and 3.5 years (late ART). Children were assessed at median ages 6.9 (CHUU, N = 61), 6.9 (early ART, N = 54), and 13.5 (late ART; N = 27) years. Children with late ART vs. children with early ART had significantly lower z scores in 7 domains, specifically global cognition, short-term memory, visuospatial processing, learning, nonverbal test performance, executive function, and motor skills (adjusted mean differences, -0.42 to -0.62, P values ≤ 0.05), and had higher odds impairment in 7 domains (adjusted odds ratios aORs, 2.87 to 16.22, P values ≤ 0.05). Children with early ART vs. CHUU had lower z scores in 5 domains (global cognition, short-term memory, delayed memory, processing speed, and behavioral regulation adjusted mean differences, -0.32 to -0.88, P values < 0.05) and higher impairment for 2 domains (short-term memory aOR, 3.88 and behavioral regulation aOR 3.46, P values < 0.05). Children with late ART vs. CHUU had lower z scores in 8 domains (adjusted mean differences, -0.57 to -1.05, P values ≤ 0.05), and higher impairment in 7 domains (aORs 1.98 to 2.32, P values ≤ 0.05).
Early ART in the first year of life attenuates but does not eliminate the neurodevelopmental compromise of HIV.
Objective
HIV stigma and discrimination is widespread in sub‐Saharan Africa and is associated with poor clinical outcomes. Schools play a critical role in the life of youth and have been identified ...as a potentially stigmatising environment. We sought to explore school HIV stigma drivers, facilitators, manifestations and outcomes among youth living with HIV (YLH) as well as potential stigma reduction interventions in Kenya.
Methods
Semi‐structured in‐depth qualitative interviews with 28 school‐attending YLH aged 14–19 years and 24 caregivers of YLH were analysed using directed content analysis. Results were summarised using the Health and Stigma Framework.
Results
Drivers and facilitators of HIV stigma in the school environment included misconceptions about HIV transmission, HIV treatment outcomes and long‐term overall health of people living with HIV. HIV stigma manifested largely as gossip, isolation and loss of friendships. Fear of HIV stigma or experienced stigma resulted in poor adherence to antiretroviral treatment—particularly among YLH in boarding schools—and poor mental health. Stigma also impacted school choice (boarding vs. day school) and prevented HIV disclosure to schools which was necessary for optimal support for care. Proposed interventions to address HIV stigma in schools included HIV education, psychosocial support for YLH, support for HIV disclosure to schools while ensuring confidentiality and building YLH resilience.
Conclusion
There is an urgent need to develop interventions to address HIV stigma in schools to ensure optimised health and social outcomes for YLH. Future studies to understand the most effective and efficient interventions are needed.
Introduction
Understanding the cost of strategies to reach and deliver pre‐exposure prophylaxis (PrEP) to priority populations is essential to assess the cost‐effectiveness and budget impact of HIV ...prevention programmes. Providing PrEP through maternal and child health and family planning clinics offers a promising strategy to reach women in high HIV burden settings. We estimated incremental costs and explored the cost drivers of integrating PrEP delivery into routine maternal and child health and family planning services in Kenya.
Methods
We conducted a costing study from the provider perspective within the PrEP Implementation for Young Women and Adolescents programme in western Kenya. We identified all within‐ and above‐facility activities supporting PrEP delivery and measured clinical service time using time‐and‐motion studies. We obtained input costs from programme budgets, expenditure records and staff interviews. We estimated changes in costs if creatinine testing were postponed from initiation to first follow‐up visit and if PrEP were prioritized to clients at high HIV risk using a behavioural risk assessment tool. We also projected costs under Ministry of Health (MOH) implementation assuming MOH salaries and programme supervision. We estimated annual numbers of PrEP visits from programme data ed from 16 facilities between November 2017 and June 2018. We report the cost per client‐month of PrEP dispensed in 2017 USD.
Results
For an annual programme output of 24,005 screenings, 4198 PrEP initiations and 4427 follow‐up visits, the average cost per client‐month of PrEP dispensed in the study was $26.52. Personnel, drugs and laboratory tests comprised 43%, 25% and 14% of programme costs respectively. Postponing creatinine testing and prioritizing PrEP delivery to clients at high HIV risk reduced total programme costs by 8% and 14% respectively. In the MOH scenario assuming no changes in outputs, the projected cost per client‐month of PrEP dispensed decreased to $16.54 and total programme costs decreased by 38%.
Conclusions
Incremental PrEP costs are sensitive to the service delivery strategy used to engage priority populations. Postponing creatinine testing and prioritizing PrEP delivery to clients at high HIV risk may reduce costs. Context‐specific cost data are crucial to assess the cost‐effectiveness and affordability of PrEP delivery models.
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