Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy (ART) in sub-Saharan Africa. Patients typically attend clinics every 1–3 months for clinical assessment, with clinic costs being comparable with costs of drugs themselves, CD4 counts are measured every 6 months, yet patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes a transition to more cost-effective ART deliver is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (“viral load”) provides a direct measure of current treatment effect. Viral load informed differentiated care is a means of tailoring care whereby those with suppressed viral load have less frequent clinical visits and attention is paid to those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach in many countries to measure viral load is by collecting dried blood spot (DBS) samples for testing in regional laboratories, although there have been concerns over the sensitivity/specificity of DBS to define treatment failure and the delay in receiving results. We use modelling to synthesize available evidence and evaluate the cost-effectiveness of viral load-informed differentiated care, account for limitations of DBS. We find that viral load-informed differentiated care using DBS is expected to be cost-effective and is recommended as the strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of future availability of point-of-care (POC) viral load tests.

Background Responses to ART among HIV-infected children in resource-limited settings have recently been reported, but outcomes vary. We sought to derive pooled estimates of the 12-month rate of virologic suppression (HIV RNA<400 copies/ml) and gain in CD4 cell percentage (ΔCD4%) for children initiating ART in resource-limited settings. Methods We conducted a systematic review and meta-analysis of published reports of HIV RNA and CD4 outcomes for treatment-naïve children (0–17 years) using the Medline, EMBASE, and LILACS electronic databases and the Cochrane Clinical Trials Register. Pooled estimates of the reported proportion with RNA<400/ml and ΔCD4% after 12 months of ART were derived using patient-level estimates and fixed- and random-effects models. To approximate “intention-to-treat” analyses, in sensitivity analyses, children with missing 12-month data were assumed to have RNA>400/ml or ΔCD4% of zero. Results Using patient-level estimates after 12-months of ART, the pooled proportion with virologic suppression was 70% (95%CI: 67–73); the pooled ΔCD4% was 13.7% (95%CI: 11.8–15.7). Results from the fixed- and random-effects models were similar. In approximated “intention-to-treat” analyses, the pooled estimates fell to 53% with virologic suppression (95%CI: 50–55) and to a ΔCD4% of 8.5% (95%CI: 5.5–11.4). Conclusions Pooled estimates of reported virologic and immunologic benefits after 12 months of ART among HIV-infected children in resource-limited settings are comparable to those observed among children in developed settings. Consistency in reporting on reasons for missing data will aid in the evaluation of ART outcomes in resource-limited settings.

Background Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa. Methods We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number ( R e ) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an R e of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters ( R e values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections. Findings When R e was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94%, increased health-care costs by 33%, and was cost-effective (ICER $340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When R e was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which R e was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced. Interpretation In South Africa, strategies involving household contact trac...

Many colleges and universities in the United States are attempting to continue undergraduate onsite learning and residential living during the COVID-19 pandemic. Modeling the outcomes, cost, and cost-effectiveness of mitigation strategies, such as social distancing, masking, and laboratory testing, can inform these efforts.

Summary Although dendritic cells are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with Zika Virus (ZIKV). Using highly-purified myeloid dendritic cells isolated from individuals with naturally-acquired acute infection, we here show that ZIKV induces profound perturbations of transcriptional signatures relative to healthy donors. Interestingly, we noted a remarkable downregulation of antiviral Interferon-stimulated genes and innate immune sensors, suggesting that ZIKV can actively suppress Interferon-dependent immune responses. In contrast, several host factors known to support ZIKV infection were strongly upregulated during natural ZIKV infection; these transcripts included AXL, the main entry receptor for ZIKV, SOCS3, a negative regulator of ISG expression, and IDO-1, a recognized inducer of regulatory T cell responses. Thus, during in vivo infection, ZIKV can transform the transcriptome of dendritic cells in favor of the virus to render these cells highly conducive to ZIKV infection.

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Key Points Question What are the projected clinical outcomes and costs associated with strategies for reducing severe acute respiratory syndrome coronavirus 2 infections among people experiencing sheltered homelessness? Findings In this decision analytic model, daily symptom screening with polymerase chain reaction (PCR) testing of individuals who had positive symptom screening paired with nonhospital care site management of people with mild to moderate coronavirus disease 2019 (COVID-19) was associated with a substantial decrease in infections and lowered costs over 4 months compared with no intervention across a wide range of epidemic scenarios. In a surging epidemic, adding periodic universal PCR testing to symptom screening and nonhospital care site management was associated with improved clinical outcomes at modestly increased costs. Meaning In this study, daily symptom screening with PCR testing of individuals who had positive symptom screening and use of alternative care sites for COVID-19 management among individuals experiencing sheltered homelessness were associated with substantially reduced new cases and costs compared with other strategies.