Developing an implementation science research agenda to improve the treatment and care outcomes among adolescents living with HIV in sub-Saharan Africa

In February 2016, Project SOAR convened a Technical Advisory Network meeting, attended by more than 50 international and domestic thought leaders in adolescent HIV care research and a small group of youth from southern Africa who are living with HIV. To prepare the groundwork for the meeting, SOAR produced a background paper synthesizing the literature on HIV continuum of care outcomes among adolescents living with HIV (ALHIV) in sub-Saharan Africa, where most adolescent cases of HIV are concentrated. This report presents the findings from the literature review and highlights from the Technical Advisory Network meeting. The first section is a summary of the review’s findings, specifically what we know about ALHIV along the care continuum. The second section of the report summarizes the outcomes from the meeting, including a set of priority research questions for the larger HIV community, as well as for Project SOAR, to consider addressing as part of new or ongoing studies

Piloting very early infant diagnosis of HIV in Lesotho: Acceptability and feasibility among mothers, health workers and laboratory personnel.

INTRODUCTION: Mortality associated with in-utero HIV infection rises rapidly within weeks after birth. Very early infant diagnosis of HIV (VEID)-testing within 2 weeks of birth-followed by immediate initiation of antiretroviral therapy has potential to avert mortality associated with in-utero transmission. However, our understanding of acceptability and feasibility of VEID is limited. METHODS: VEID was piloted in an observational prospective cohort of HIV-positive pregnant women and their infants in 13 Lesotho health facilities. Between March-July 2016, semi-structured interviews were conducted with HIV-positive women attending 6-week or 14-week postnatal visits and health workers (HWs) in 8 study facilities in 3 districts as well as with district and central laboratory staff. Interview themes included acceptability of birth and subsequent HIV testing and early treatment, perceived VEID challenges, and HIV birth testing procedures and how well they were performed. RESULTS: Interviews were conducted with 20 women, 18 HWs and 9 district/central laboratory staff. Nearly all mothers perceived knowing their child\u27s HIV status at birth positively. Mothers and HWs did not indicate that birth testing affected subsequent acceptance of infant HIV testing or clinic attendance. HWs and laboratory staff reported weak follow-up systems for mothers with home deliveries, and concern regarding the increased workload associated with additional testing requirements. All groups reported turnaround time delays for EID, and that sometimes results were never received. CONCLUSIONS: Women, HWs, and laboratory staff found VEID acceptable and were supportive of national implementation of birth testing. However, they identified challenges within the EID system that could be exacerbated by adding a test to the diagnostic algorithm, such as delays in receiving test results, suggesting VEID may not be feasible in certain settings. Policymakers will need to consider whether adding birth testing or strengthening the current clinic and laboratory system is the most appropriate course of action

World Health Organization Generic Protocol to Assess Drug-Resistant HIV Among Children <18 Months of Age and Newly Diagnosed With HIV in Resource-Limited Countries

Increased use of nonnucleoside reverse transcriptase inhibitors (NNRTIs) in pregnant and breastfeeding women will result in fewer children infected with human immunodeficiency virus (HIV). However, among children infected despite prevention of mother-to-child transmission (PMTCT), a substantial proportion will acquire NNRTI-resistant HIV, potentially compromising response to NNRTI-based antiretroviral therapy (ART). In countries scaling up PMTCT and pediatric ART programs, it is crucial to assess the proportion of young children with drug-resistant HIV to improve health outcomes and support national and global decision making on optimal selection of pediatric first-line ART. This article summarizes a new World Health Organization surveillance protocol to assess resistance using remnant dried blood spot specimens from a representative sample of children aged <18 months being tested for early infant diagnosi

Improving estimates of children living with HIV from the Spectrum AIDS Impact Model

Objective: Estimated numbers of children living with HIV determine programmatic and treatment needs. We explain the changes made to the UNAIDS estimates between 2015 and 2016, and describe the challenges around these estimates. Methods: Estimates of children newly infected, living with HIV, and dying of AIDS are developed by country teams using Spectrum software. Spectrum files are available for 160 countries, which represent 98% of the global population. In 2016, the methods were updated to reflect the latest evidence on mother-to-child HIV transmission and improved assumptions on the age children initiate antiretroviral therapy. We report updated results using the 2016 model and validate these estimates against mother-to-child transmission rates and HIV prevalence from population-based surveys for the survey year. Results: The revised 2016 model estimates 27% fewer children living with HIV in 2014 than the 2015 model, primarily due to changes in the probability of mother-to-child transmission among women with incident HIV during pregnancy. The revised estimates were consistent with population-based surveys of HIV transmission and HIV prevalence among children aged 5–9 years, but were lower than surveys among children aged 10–14 years. Conclusions: The revised 2016 model is an improvement on previous models. Paediatric HIV models will continue to evolve as further improvements are made to the assumptions. Commodities forecasting and programme planning rely on these estimates, and increasing accuracy will be critical to enable effective scale-up and optimal use of resources. Efforts are needed to improve empirical measures of HIV prevalence, incidence, and mortality among children

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort

BACKGROUND: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. METHODS: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. RESULTS: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. CONCLUSIONS: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years

Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis

Article approval pendingEvidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39)

Timing of antiretroviral therapy and adverse pregnancy outcomes : a systematic review and meta-analysis

BACKGROUND: Although life-long combination antiretroviral therapy (ART) is recommended for all HIV-infected individuals, there are limited data on pregnancy outcome with ART initiation pre-conception. We assessed the safety of ART initiated pre-conception versus post-conception on adverse pregnancy outcome. METHODS: We conducted a systematic review of studies from low-, middle-, and high-income countries. We searched Cochrane Central Register of Controlled Trials, EMBASE, LILACS, MEDLINE for randomized trials, quasi-randomized trials and prospective cohort studies conducted between 01 January 1980 to 01 June 2016). Risk ratios were pooled using a random-effects model. FINDINGS: Eleven studies were included (N=19,189 mother-infant pairs). Women initiating ART pre-conception compared to post-conception were significantly more likely to deliver preterm (pooled risk ratio[RR]=1·20, 95% confidence interval[CI] 1·01-1·14, 10 studies), very preterm (RR=1·53, 95%CI 1·22-1·92, two studies), or have low birth weight (LBW) infants (RR=1·30, 95%CI 1·04-1·62, two studies). Data on neonatal mortality was limited. We found no increase in very LBW (RR=0.18, 95% CI 0.02-1.51, one study), small for gestational age (SGA) (RR = 1·13, 95% CI 0·94-1·35, two studies), severe SGA (RR=1·09, 95%CI 0·82-1·45, one study), stillbirth (RR= RR=1·30, 95% CI 0·99-1·69, two studies) or congenital anomalies (RR= RR=1·24, 95% CI 0·61-2·49, one study). INTERPRETATION: The benefits of ART for maternal health and prevention of perinatal transmission outweigh risks, but there remain limited, poor quality data on the extent/severity of these risks. We found elevated preterm delivery and low birth weight rates associated with pre-conception ART. As pre-conception ART rapidly increases globally, it will be critical to monitor for potential adverse pregnancy outcomes

Barriers to provider-initiated testing and counselling for children in a high HIV prevalence setting: a mixed methods study.

BACKGROUND: There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children. METHODS AND FINDINGS: Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive. CONCLUSIONS: The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed