Cost-effectiveness of Routine Provider-Initiated Testing and Counseling for Children With Undiagnosed HIV in South Africa.

BACKGROUND: We compared the cost-effectiveness of pediatric provider-initiated HIV testing and counseling (PITC) vs no PITC in a range of clinical care settings in South Africa. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications Pediatric model to simulate a cohort of children, aged 2-10 years, presenting for care in 4 settings (outpatient, malnutrition, inpatient, tuberculosis clinic) with varying prevalence of undiagnosed HIV (1.0%, 15.0%, 17.5%, 50.0%, respectively). We compared "PITC" (routine testing offered to all patients; 97% acceptance and 71% linkage to care after HIV diagnosis) with no PITC. Model outcomes included life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs) from the health care system perspective and the proportion of children with HIV (CWH) diagnosed, on antiretroviral therapy (ART), and virally suppressed. We assumed a threshold of $3200/year of life saved (YLS) to determine cost-effectiveness. Sensitivity analyses varied the age distribution of children seeking care and costs for PITC, HIV care, and ART. RESULTS: PITC improved the proportion of CWH diagnosed (45.2% to 83.2%), on ART (40.8% to 80.4%), and virally suppressed (32.6% to 63.7%) at 1 year in all settings. PITC increased life expectancy by 0.1-0.7 years for children seeking care (including those with and without HIV). In all settings, the ICER of PITC vs no PITC was very similar, ranging from $710 to $1240/YLS. PITC remained cost-effective unless undiagnosed HIV prevalence was <0.2%. CONCLUSIONS: Routine testing improves HIV clinical outcomes and is cost-effective in South Africa if the prevalence of undiagnosed HIV among children exceeds 0.2%. These findings support current recommendations for PITC in outpatient, inpatient, tuberculosis, and malnutrition clinical settings.

PEPFAR's response to the convergence of the HIV and COVID-19 pandemics in Sub-Saharan Africa.

INTRODUCTION: The COVID-19 pandemic reached the African continent in less than three months from when the first cases were reported from mainland China. As COVID-19 preparedness and response plans were rapidly instituted across sub-Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID-19 pandemic would have in under-resourced settings with high burdens of PLHIV. The potential negative impact of COVID-19 in these countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality of PLHIV, requiring countries to leverage existing HIV care systems to propel COVID-19 responses, while safeguarding PLHIV and HIV programme gains. In anticipation of COVID-19-related disruptions, PEPFAR promptly established guidance to rapidly adapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID-19. This commentary reviews PEPFAR's COVID-19 technical guidance and provides country-specific examples of programme adaptions in sub-Saharan Africa. DISCUSSION: The COVID-19 pandemic may pose significant risks to the continuity of HIV services, especially in countries with high HIV prevalence and weak and over-burdened health systems. Although there is currently limited understanding of how COVID-19 affects PLHIV, it is imperative that public health systems and academic centres monitor the impact of COVID-19 on PLHIV. The general principles of the HIV programme adaptation guidance from PEPFAR prioritize protecting the gains in the HIV response while minimizing in-person home and facility visits and other direct contact when COVID-19 control measures are in effect. PEPFAR-supported clinical, laboratory, supply chain, community and data reporting systems can play an important role in mitigating the impact of COVID-19 in sub-Saharan Africa. CONCLUSIONS: As community transmission of COVID-19 continues and the number of country cases rise, fragile health systems may be strained. Utilizing the adaptive, data-driven programme approaches in facilities and communities established and supported by PEPFAR provides the opportunity to strengthen the COVID-19 response while protecting the immense gains spanning HIV prevention, testing and treatment reached thus far.

Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines.

BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens. METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain. INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. FUNDING: Bill & Melinda Gates Foundation.

Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries.

INTRODUCTION: Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. DISCUSSION: The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. CONCLUSIONS: GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets.

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa.

INTRODUCTION: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. METHODS: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. RESULTS: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. CONCLUSIONS: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy.

Building Sustainable Local Capacity for Global Health Research in West Africa.

BACKGROUND: Global health research in resource-limited countries has been largely sponsored and led by foreign institutions. Thus, these countries' training capacity and productivity in global health research is limited. Local participation at all levels of global health knowledge generation promotes equitable access to evidence-based solutions. Additionally, leadership inclusive of competent local professionals promotes best outcomes for local contextualization and implementation of successful global health solutions. Among the sub-Saharan African regions, West Africa in particular lags in research infrastructure, productivity, and impact in global health research. OBJECTIVE: In this paper, experts discuss strategies for scaling up West Africa's participation in global health evidence generation using examples from Ghana and Nigeria. METHODS: We conducted an online and professional network search to identify grants awarded for global health research and research education in Ghana and Nigeria. Principal investigators, global health educators, and representatives of funding institutions were invited to add their knowledge and expertise with regard to strengthening research capacity in West Africa. FINDINGS: While there has been some progress in obtaining foreign funding, foreign institutions still dominate local research. Local research funding opportunities in the 2 countries were found to be insufficient, disjointed, poorly sustained, and inadequately publicized, indicating weak infrastructure. As a result, research training programs produce graduates who ultimately fail to launch independent investigator careers because of lack of mentoring and poor infrastructural support. CONCLUSIONS: Research funding and training opportunities in Ghana and Nigeria remain inadequate. RECOMMENDATIONS: We recommend systems-level changes in mentoring, collaboration, and funding to drive the global health research agenda in these countries. Additionally, research training programs should be evaluated not only by numbers of individuals graduated but also by numbers of independent investigators and grants funded. Through equitable collaborations, infrastructure, and mentoring, West Africa can match the rest of Africa in impactful global health research.

National Institutes of Health investment in studies of HIV disclosure to children.

The goals of this manuscript will be to review current and past National Institutes of Health (NIH) funding on maternal and child HIV disclosure research and lay out current research gaps in these areas. Examples of work funded by NIH will highlight how the disclosure needs of families affected by HIV have changed over the past 30 years as well as highlight what we have learned. The review will include the recent NICHD RFA that focused specifically on disclosure of HIV status to children in low and middle-income country settings. A brief description of findings from these NIH-funded grants will be provided. The authors will then describe current research gaps and challenges as they relate to research on HIV disclosure both in the U.S. and internationally.

Preexposure prophylaxis for adolescents and young adults at risk for HIV infection: is an ounce of prevention worth a pound of cure?

An alarming proportion of incident human immunodeficiency virus (HIV) infections worldwide occur in youth. In the United States, 69% of all new infections among youth occurred in young men who have sex with men (YMSM). Recent studies show the promise of preexposure prophylaxis (PrEP) for preventing HIV infection, but research efforts suffer from disproportionately low representation of the youth who are most at risk. Youth-focused research is critical and should include behavioral, community, and biomedical interventions to create a comprehensive HIV prevention package. The many ethical, legal, and regulatory considerations in conducting HIV research among, and in providing care services to, youth must be addressed so that those at high risk and most likely to benefit can have unfettered access to safe and effective health-promoting interventions. YMSM and minority youth are at substantial HIV risk and urgently need effective HIV prevention tools for which the short and long-term benefits and risks have been carefully considered.

Viral load predicts new world health organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy, independent of CD4 T lymphocyte value.

BACKGROUND: Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. METHODS: The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. RESULTS: The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. CONCLUSIONS: Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

Increase in tuberculin skin test converters among health care workers after a change from Tubersol to Aplisol.

BACKGROUND: Comparability of the 2 commercially available tuberculin skin testing (TST) preparations, Aplisol (Parkdale Pharmaceuticals, Inc, Rochester, MI) and Tubersol (Aventis Pasteur, Inc, Swiftwater, PA), remains uncertain, particularly in groups that undergo repeated testing, such as health care workers. METHODS: Data from the annual tuberculosis screening program for health care workers at the Kennedy Krieger Institute in Baltimore, Maryland, were analyzed. Conversion rates during 1997-2003 in workers screened with Tubersol (n = 8897 screenings) were compared with 1203 workers who underwent screening with Aplisol in 2004. Repeat testing with Tubersol was examined in those who converted in 2004 with Aplisol. RESULTS: Annual TST conversion rates ranged from 0.3% to 0.9% between 1997 and 2003 using Tubersol. After switching to Aplisol in 2004, the TST conversion rate significantly increased to 2% (P < .001). Among 24 health care workers who were converters with Aplisol in 2004, only 6 of 23 (26%) were converters on repeat testing with Tubersol (1 declined retesting). None of the apparent converters (n = 24) had radiographic evidence of Mycobacterium tuberculosis infection, and there was no epidemiologic evidence of transmission. Reclassification based on Tubersol testing in 2004 resulted in conversion rates comparable with previous years. CONCLUSION: We conclude that the change from Tubersol to Aplisol resulted in falsely elevated conversion rates. Our results support the guidelines from the Centers for Disease Control and Prevention recommendations that 1 product should be used consistently in populations undergoing periodic testing.

Hospital and outpatient health services utilization among HIV-infected children in care 2000-2001.

BACKGROUND: The aging of the pediatric HIV cohort and advances in antiretroviral therapy for children may have resulted in recent changes in patterns of healthcare utilization. OBJECTIVES: The objectives of this study were to examine inpatient and outpatient HIV-related health service utilization in a multistate sample of HIV-infected children, and to assess sociodemographic and clinical correlates of utilization. DESIGN: Cohort study of pediatric patients with HIV. Demographic, clinical, and resource utilization data were collected from medical records for 2000 and 2001. SETTING: This study was conducted at 4 U.S. HIV primary pediatric and specialty care sites in different geographic regions. PATIENTS: Three hundred three HIV-positive children with at least one outpatient visit or CD4 test in either 2000 or 2001 were studied. MAIN OUTCOME MEASURES: Mean outcome measures were number of hospital admissions, mean length of hospital stay, and number of outpatient clinic/office visits. RESULTS: Hospitalization rates decreased significantly from 39.2 (95% confidence interval [CI], 28.4-50.1) to 25.3 (95% CI, 16.4-34.3) admissions per 100 patients between 2000 and 2001. Hospitalizations were higher among patients with greater immunosuppression, those 2 years and under, and those with AIDS, but were not significantly related to receipt of highly active antiretroviral therapy. Mean outpatient visits did not change significantly between 2000 and 2001 from 9.09 (95% CI, 8.3-9.9) to 9.06 (95% CI, 8.4-9.7) visits per child per year. Children 2 years and under, those on highly active antiretroviral therapy, those with AIDS, and those with Medicaid had significantly higher outpatient utilization. Those with higher HIV-1 RNA had higher outpatient utilization than those with less advanced disease. CONCLUSION: Inpatient utilization significantly decreased between 2000 and 2001, but outpatient utilization did not change over time. Compared with prior studies, utilization rates appear to be declining over time. Unlike adults, racial/ethnic or gender disparities in healthcare utilization are less pronounced for HIV-infected children.