Associations between HIV Antiretroviral Therapy and the Prevalence and Incidence of Pregnancy in Rakai, Uganda

Background. Use of antiretroviral therapy (ART) may be associated with higher pregnancy rates. Methods. The prevalence and incidence of pregnancy was assessed in 712 HIV+ pre-ART women of reproductive age (WRA) (15–45) and 244 HIV+ WRA initiating ART. Prevalence rate ratios (PRR), incidence rate ratios (IRR), and 95% confidence interval (CI) were assessed. Results. The incidence of pregnancy was 13.1/100 py among women in pre-ART care compared to 24.6/100 py among women on ART (IRR = 0.54; 95% CI 0.37, 0.81, p < 0.0017). The prevalence of pregnancy at ART initiation was 12.0% with CD4 counts 100–250 compared with 3.2% with CD4 <100 (PRR = 3.24, CI 1.51–6.93), and the incidence of pregnancy while on ART was highest in women with a good immunologic response. Desire for more children was a very important factor in fertility. Conclusion. ART was associated with increased pregnancy rates in HIV+ women, particularly those with higher CD4 counts and good immunologic response to therapy, suggesting a need to strengthen reproductive health services for both women and their partners that could address their fertility decisions/intentions particularly after ART initiation

From policy to practice: exploring the implementation of antiretroviral therapy access and retention policies between 2013 and 2016 in six sub-Saharan African countries

Background: Understanding the implementation of 2013 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at the facility level provides important lessons for the roll-out of future HIV policies. Methods: A national policy review was conducted in six sub-Saharan African countries to map the inclusion of the 2013 WHO HIV treatment recommendations. Twenty indicators of policy adoption were selected to measure ART access (n = 12) and retention (n = 8). Two sequential cross-sectional surveys were conducted in facilities between 2013/2015 (round 1) and 2015/2016 (round 2) from ten health and demographic surveillance sites in Kenya, Malawi, South Africa, Tanzania, Uganda and Zimbabwe. Using standardised questionnaires, facility managers were interviewed. Descriptive analyses were used to assess the change in the proportion of facilities that implemented these policy indicators between rounds. Results: Although, expansion of ART access was explicitly stated in all countries’ policies, most lacked policies that enhanced retention. Overall, 145 facilities were included in both rounds. The proportion of facilities that initiated ART at CD4 counts of 500 or less cells/μL increased between round 1 and 2 from 12 to 68%, and facilities initiating patients on 2013 WHO recommended ART regimen increased from 42 to 87%. There were no changes in the proportion of facilities reporting stock-outs of first-line ART in the past year (18 to 11%) nor in the provision of three-month supply of ART (43 to 38%). None of the facilities provided community-based ART delivery. Conclusion: The increase in ART initiation CD4 threshold in most countries, and substantial improvements made in the provision of WHO recommended first-line ART regimens demonstrates that rapid adoption of WHO recommendations is possible. However, improved logistics and resources and/or changes in policy are required to further minimise ART stock-outs and allow lay cadres to dispense ART in the community. Increased efforts are needed to offer longer durations between clinic visits, a strategy purported to improve retention. These changes will be important as countries move to implement the revised 2015 WHO guidelines to initiate all HIV positive people onto ART regardless of their immune statu

The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA):Data on mortality, by HIV status and stage on the HIV care continuum, among the general population in seven longitudinal studies between 1989 and 2014

Timely progression of people living with HIV (PLHIV) from the point of infection through the pathway from diagnosis to treatment is important in ensuring effective care and treatment of HIV and preventing HIV-related deaths and onwards transmission of infection. Reliable, population-based estimates of new infections are difficult to obtain for the generalised epidemics in sub-Saharan Africa. Mortality data indicate disease burden and, if disaggregated along the continuum from diagnosis to treatment, can also reflect the coverage and quality of different HIV services. Neither routine statistics nor observational clinical studies can estimate mortality prior to linkage to care nor following disengagement from care. For this, population-based data are required.The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa brings together studies in Kenya, Malawi, South Africa, Tanzania, Uganda, and Zimbabwe. Eight studies have the necessary data to estimate mortality by HIV status, and seven can estimate mortality at different stages of the HIV care continuum. This data note describes a harmonised dataset containing anonymised individual-level information on survival by HIV status for adults aged 15 and above. Among PLHIV, the dataset provides information on survival during different periods: prior to diagnosis of infection; following diagnosis but before linkage to care; in pre-antiretroviral treatment (ART) care; in the first six months after ART initiation; among people continuously on ART for 6+ months; and among people who have ever interrupted ART

Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial

BACKGROUND:  If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS:  Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects. RESULTS:  Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040). CONCLUSIONS:  Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low. CLINICAL TRIALS REGISTRATION:  ISRCTN58046240

Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial

Background Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. Methods and Findings Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. Conclusions In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation

Data resource profile: network for analysing longitudinal population-based HIV/AIDS data on Africa (ALPHA Network)

The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network, http://alpha.lshtm.ac.uk/) brings together ten population-based HIV surveillance sites in eastern and southern Africa, and is coordinated by the London School of Hygiene and Tropical Medicine (LSHTM). It was established in 2005 and aims to (i) broaden the evidence base on HIV epidemiology for informing policy, (ii) strengthen the analytical capacity for HIV research, and (iii) foster collaboration between network members. All study sites, some starting in the late 1980s and early 1990s, conduct demographic surveillance in populations that range from approximately 20 to 220 thousand individuals. In addition, they conduct population-based surveys with HIV testing, and verbal autopsy interviews with relatives of deceased residents. ALPHA Network datasets have been used for studying HIV incidence, sexual behaviour and the effects of HIV on mortality, fertility, and household composition. One of the network’s substantive focus areas is the monitoring of AIDS mortality and HIV services coverage in the era of antiretroviral therapy. Service use data are retrospectively recorded in interviews and supplemented by information from record linkage with medical facilities in the surveillance areas. Data access is at the discretion of each of the participating sites, but can be coordinated by the network

A Single-Blind randomized controlled trial to evaluate the effect of extended counseling on uptake of pre-antiretroviral care in eastern uganda

<p>Abstract</p> <p>Background</p> <p>Many newly screened people living with HIV (PLHIV) in Sub-Saharan Africa do not understand the importance of regular pre-antiretroviral (ARV) care because most of them have been counseled by staff who lack basic counseling skills. This results in low uptake of pre-ARV care and late treatment initiation in resource-poor settings. The effect of providing post-test counseling by staff equipped with basic counseling skills, combined with home visits by community support agents on uptake of pre-ARV care for newly diagnosed PLHIV was evaluated through a randomized intervention trial in Uganda.</p> <p>Methods</p> <p>An intervention trial was performed consisting of post-test counseling by trained counselors, combined with monthly home visits by community support agents for continued counseling to newly screened PLHIV in Iganga district, Uganda between July 2009 and June 2010, Participants (N = 400) from three public recruitment centres were randomized to receive either the intervention, or the standard care (the existing post-test counseling by ARV clinic staff who lack basic training in counseling skills), the control arm. The outcome measure was the proportion of newly screened and counseled PLHIV in either arm who had been to their nearest health center for clinical check-up in the subsequent three months +2 months. Treatment was randomly assigned using computer-generated random numbers. The statistical significance of differences between the two study arms was assessed using chi-square and t-tests for categorical and quantitative data respectively. Risk ratios and 95% confidence intervals were used to assess the effect of the intervention.</p> <p>Results</p> <p>Participants in the intervention arm were 80% more likely to accept (take up) pre-ARV care compared to those in the control arm (RR 1.8, 95% CI 1.4-2.1). No adverse events were reported.</p> <p>Conclusions</p> <p>Provision of post-test counseling by staff trained in basic counseling skills, combined with home visits by community support agents had a significant effect on uptake of pre-ARV care and appears to be a cost-effective way to increase the prerequisites for timely ARV initiation.</p> <p>Trial registration</p> <p>The trial was registered by Current Controlled Trials Ltd C/OBioMed Central Ltd as <a href="http://www.controlled-trials.com/ISRCTN94133652">ISRCTN94133652</a> and received financial support from Sida and logistical support from the European Commission.</p

Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Background International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population. Findings Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4–7·3) of transmissions occurred within lakeside areas, 89·2% (86·0–91·8) within inland areas, 1·3% (0·6–2·6) from lakeside to inland areas, and 3·7% (2·3–5·8) from inland to lakeside areas. Interpretation Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics. Funding The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention