A Global Research Agenda for Pediatric HIV.

BACKGROUND: Despite progress, 2016 still saw 160,000 new infections and 120,000 AIDS-related deaths among children. Evidence gaps on how to best diagnose, treat, and deliver services to children living with HIV remain. A global research prioritization exercise was undertaken by WHO and CIPHER to focus research efforts in the context of diminishing resources. METHODS: The Child Health and Nutrition Research Initiative methodology was adapted and used, as described by Irvine et al. Outcomes were reviewed by an expert group and 5 priority themes identified for testing, antiretroviral treatment, and service delivery, accounting for existing policies, published literature and ongoing research. RESULTS: A total of 749 questions were submitted by 269 individuals from 62 countries. For HIV testing, priority themes included strategies and interventions to improve access, uptake and linkage to care, including with novel diagnostic tools and entry points beyond antenatal care. For treatment, priorities included strategies to improve adherence, short- and long-term outcomes and management of coinfections, optimal drug formulations, and early ART. For service delivery, priorities included strategies or interventions to improve access, uptake and retention in care, including psychosocial and family support and approaches to HIV disclosure and reduction of stigma and discrimination. CONCLUSIONS: This is the largest Child Health and Nutrition Research Initiative exercise undertaken in HIV. The results provide guidance to focus future research in pediatric HIV for impact. Global commitment to support priority research, adequate investment, and strong leadership is urgently needed to improve the health and well-being of children living with and affected by HIV.

HIV birth testing and linkage to care for HIV-infected infants.

: On 5-6 May 2016, the division of AIDS of the National Institute of Allergy and Infectious Diseases convened a workshop on 'HIV Birth Testing and Linkage to Care for HIV Infected Infants.' The goal of the workshop was to evaluate birth testing for early infant diagnosis (EID) of HIV, delineate technological resources for advancing a point-of-care (POC) HIV test implementable at birth and chart out the implementation hurdles for initiating early antiretroviral therapy to HIV-infected infants diagnosed at birth. The workshop addressed research and regulatory needs involved in the optimization of POC EID testing and challenges associated with implementation of EID, focusing on testing at birth. Scientific gaps and areas of intervention to accelerate and scale-up EID initiatives and birth testing were identified. These include discussion of the evidence supporting an early mortality peak among HIV-infected infant and justifying a role for birth HIV testing, including POC testing; evaluation of the current POC EID technology pipeline and test performance characteristics required for effective programmatic uptake; mathematical modeling of different testing scenarios and solutions with inclusion of birth testing; the adoption of setting-specific EID testing algorithms to achieve efficient linkage to care including early antiretroviral therapy initiation; the development of appropriate quality assurance programs to ensure accuracy of test results and enable sustainability of the testing program. Addressing these gaps and answering these challenges will be important in helping improve outcomes for HIV-infected infants and accelerate achieving the Joint United Nations Program for HIV and AIDS 90-90-90 targets in children.

Improving Retention in Care Among Pregnant Women and Mothers Living With HIV: Lessons From INSPIRE and Implications for Future WHO Guidance and Monitoring.

Identifying women living with HIV, initiating them on lifelong antiretroviral treatment (ART), and retaining them in care are among the important challenges facing this generation of health care managers and public health researchers. Implementation research attempts to solve a wide range of implementation problems by trying to understand and work within real-world conditions to find solutions that have a measureable impact on the outcomes of interest. Implementation research is distinct from clinical research in many ways yet demands similar standards of conceptual thinking and discipline to generate robust evidence that can be, to some extent, generalized to inform policy and service delivery. In 2011, the World Health Organization (WHO), with funding from Global Affairs Canada, began support to 6 implementation research projects in Malawi, Nigeria, and Zimbabwe. All focused on evaluating approaches for improving rates of retention in care among pregnant women and mothers living with HIV and ensuring their continuation of ART. This reflected the priority given by ministries of health, program implementers, and researchers in each country to the importance of women living with HIV returning to health facilities for routine care, adherence to ART, and improved health outcomes. Five of the studies were cluster randomized controlled trials, and 1 adopted a matched cohort design. Here, we summarize some of the main findings and key lessons learned. We also consider some of the broader implications, remaining knowledge gaps, and how implementation research is integral to, and essential for, global guideline development and to inform HIV/AIDS strategies.

A systematic review of interventions to improve postpartum retention of women in PMTCT and ART care.

INTRODUCTION: The World Health Organization recommends lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV. Effective transitioning from maternal and child health to ART services, and long-term retention in ART care postpartum is crucial to the successful implementation of lifelong ART for pregnant women. This systematic review aims to determine which interventions improve (1) retention within prevention of mother-to-child HIV transmission (PMTCT) programmes after birth, (2) transitioning from PMTCT to general ART programmes in the postpartum period, and (3) retention of postpartum women in general ART programmes. METHODS: We searched Medline, Embase, ISI Web of Knowledge, the regional World Health Organization databases and conference abstracts for data published between 2002 and 2015. The quality of all included studies was assessed using the GRADE criteria. RESULTS AND DISCUSSION: After screening 8324 records, we identified ten studies for inclusion in this review, all of which were from sub-Saharan Africa except for one from the United Kingdom. Two randomized trials found that phone calls and/or text messages improved early (six to ten weeks) postpartum retention in PMTCT. One cluster-randomized trial and three cohort studies found an inconsistent impact of different levels of integration between antenatal care/PMTCT and ART care on postpartum retention. The inconsistent results of the four identified studies on care integration are likely due to low study quality, and heterogeneity in intervention design and outcome measures. Several randomized trials on postpartum retention in HIV care are currently under way. CONCLUSIONS: Overall, the evidence base for interventions to improve postpartum retention in HIV care is weak. Nevertheless, there is some evidence that phone-based interventions can improve retention in PMTCT in the first one to three months postpartum.

Pediatric treatment 2.0: ensuring a holistic response to caring for HIV-exposed and infected children.

Treatment 2.0 is an initiative launched by UNAIDS and WHO in 2011 to catalyze the next phase of treatment scale-up for HIV. The initiative defines strategic activities in 5 key areas, drugs, diagnostics, commodity costs, service delivery and community engagement in an effort to simplify treatment, expand access and maximize program efficiency. For adults, many of these activities have already been turned into treatment policies. The recent WHO recommendation to use a universal first line regimen regardless of gender, pregnancy and TB status is a treatment simplification very much in line with Treatment 2.0. But despite that fact that Treatment 2.0 encompasses all people living with HIV, we have not seen the same evolution in policy development for children. In this paper we discuss how Treatment 2.0 principles can be adapted for the pediatric population. There are several intrinsic challenges. The need for distinct treatment regimens in children of different ages makes it hard to define a one size fits all approach. In addition, the fact that many providers are reluctant to treat children without the advice of specialists can hamper decentralization of service delivery. But at the same time, there are opportunities that can be availed now and in the future to scale up pediatric treatment along the lines of Treatment 2.0. We examine each of the five pillars of Treatment 2.0 from a pediatric perspective and present eight specific action points that would result in simplification of pediatric treatment and scale up of HIV services for children.

Early treatment of HIV: implications for resource-limited settings.

PURPOSE OF REVIEW: We review the current literature supporting adoption of higher CD4 thresholds for initiation of antiretroviral treatment and survey progress in adoption of early treatment policies in resource-limited settings. We highlight some of the challenges and opportunities implementation of early treatment will bring. RECENT FINDINGS: The initial success of combination antiretroviral treatment resulted in the recommendation to treat early all individuals with HIV. However, the gradual realization that antiretroviral treatment was associated with toxicity led to a more tempered approach. Recent cohort studies and some clinical trials have shown that delaying treatment is associated with increased morbidity and mortality. SUMMARY: Early treatment is routinely practiced in developed countries. Now, early treatment is being adopted as a strategy in many resource-limited settings. The implications of this policy shift are not known, but we predict early treatment will have important consequences for the health system, the individual, and the community. Whereas these consequences will bring significant challenges, the increased numbers of HIV-infected individuals on treatment will result in many new opportunities - antiretroviral treatment will become less expensive, systems to deliver chronic care will be strengthened, and the policy shift will focus greater attention on pregnant women and children. Finally, some authors postulate that early treatment may impact HIV transmission.

Recombinant glycoprotein vaccines for human immunodeficiency virus-infected children and their effects on viral quasispecies.

In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease.