Nello Blaser

Missed opportunities to prevent mother-to-child-transmission: systematic review and meta-analysis

Objectives:To determine magnitude and reasons of loss to program and poor antiretroviral prophylaxis coverage in prevention of mother-to-child transmission (PMTCT) programs in sub-Saharan Africa. Design:Systematic review and meta-analysis. Methods:We searched PubMed and Embase databases for PMTCT studies in sub-Saharan Africa published between January 2002 and March 2012. Outcomes were the percentage of pregnant women tested for HIV, initiating antiretroviral prophylaxis, having a CD4 cell count measured, and initiating antiretroviral combination therapy (cART) if eligible. In children outcomes were early infant diagnosis for HIV, and cART initiation. We combined data using random-effects meta-analysis and identified predictors of uptake of interventions. Results:Forty-four studies from 15 countries including 75 172 HIV-infected pregnant women were analyzed. HIV-testing uptake at antenatal care services was 94% [95% confidence intervals (CIs) 92–95%] for opt-out and 58% (95% CI 40–75%) for opt-in testing. Coverage with any antiretroviral prophylaxis was 70% (95% CI 64–76%) and 62% (95% CI 50–73%) of pregnant women eligible for cART received treatment. Sixty-four percent (95% CI 48–81%) of HIV exposed infants had early diagnosis performed and 55% (95% CI 36–74%) were tested between 12 and 18 months. Uptake of PMTCT interventions was improved if cART was provided at the antenatal clinic and if the male partner was involved. Conclusion:In sub-Saharan Africa, uptake of PMTCT interventions and early infant diagnosis is unsatisfactory. An integrated family-centered approach seems to improve retention.

Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models

BACKGROUND WHOs 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. METHODS We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. FINDINGS All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. INTERPRETATION The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. FUNDING Bill & Melinda Gates Foundation, WHO.

Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

Background:Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. Design:Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. Methods:Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. Results:POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US

Targeted Maximum Likelihood Estimation for Dynamic and Static Longitudinal Marginal Structural Working Models.

5 and US

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study

20 and detection limits between 1000 and 10 000 copies/ml, the ICER of POC-VL was US

Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis.

4010–US

Impact of viral load and the duration of primary infection on HIV transmission

9230 compared with clinical and US

Tracing of patients lost to follow-up and HIV transmission: mathematical modeling study based on 2 large ART programs in Malawi.

5960–US

Tuberculosis in Cape Town: An age-structured transmission model

25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US

The Cost-Effectiveness of Monitoring Strategies for Antiretroviral Therapy of HIV Infected Patients in Resource-Limited Settings: Software Tool.

2450–US