Background US and international agencies have signaled their commitment to containing the HIV epidemic via early case identification and linkage to antiretroviral therapy (ART) immediately upon diagnosis. We forecast outcomes of this approach if implemented in Washington DC. Methods Using a mathematical model of HIV case detection and treatment, we evaluate combinations of HIV screening and ART initiation strategies. We define current practice as no regular screening program and ART at ≤350/μl, and test and treat as annual screening and ART upon diagnosis. Outcomes include life expectancy of HIV-infected persons and changes in the population time with transmissible HIV RNA. Data, largely from DC, include undiagnosed HIV prevalence 0.6%, annual incidence 0.13%, 31% test offer, 60% acceptance, and 50% linkage to care. Input parameters, including optimized ART efficacy, are varied in sensitivity analyses. Results Projected life expectancies, from an initial mean age 41 years, for current practice, test and treat, and test and treat with optimized ART are 23.9, 25.0, and 25.6 years. Compared to current practice, test and treat leads to a 14.7% reduction in time spent with transmissible HIV RNA in the next 5 years; test and treat with optimized ART results in a 27.2% reduction. Conclusions An expanded HIV test and treat program in Washington DC will increase life expectancy of HIV-infected patients but will have a modest impact on HIV transmission over the next five years and is unlikely to halt the HIV epidemic. Summary The CEPAC model shows a test and treat strategy in Washington DC would result in a substantial clinical impact to HIV-infected individuals. Results suggest a need to temper expectations regarding the extent to which test and treat will control the epidemic.

Background Although 900,000 HIV-infected South Africans receive antiretroviral therapy (ART), the majority of South Africans with HIV remain undiagnosed. Methods We use a published simulation model of HIV case detection and treatment to examine three HIV screening scenarios, in addition to current practice: 1) one-time; 2) every five years; and 3) annually. South African model input data include: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including two sequential ART regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. Results HIV screening one-time, every five years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6 and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every five years. Screening every five years and annually each have incremental cost-effectiveness ratios of $1,570/quality-adjusted life year (QALY) and $1,720/QALY. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. Conclusions In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment.

BackgroundComputer simulation models can project long-term patient outcomes and inform health policy. We internally validated and then calibrated a model of HIV disease in children before initiation of antiretroviral therapy to provide a framework against which to compare the impact of pediatric HIV treatment strategies.MethodsWe developed a patient-level (Monte Carlo) model of HIV progression among untreated children <5 years of age, using the Cost-Effectiveness of Preventing AIDS Complications model framework: the CEPAC-Pediatric model. We populated the model with data on opportunistic infection and mortality risks from the International Epidemiologic Database to Evaluate AIDS (IeDEA), with mean CD4% at birth (42%) and mean CD4% decline (1.4%/month) from the Women and Infants’ Transmission Study (WITS). We internally validated the model by varying WITS-derived CD4% data, comparing the corresponding model-generated survival curves to empirical survival curves from IeDEA, and identifying best-fitting parameter sets as those with a root-mean square error (RMSE) <0.01. We then calibrated the model to other African settings by systematically varying immunologic and HIV mortality-related input parameters. Model-generated survival curves for children aged 0-60 months were compared, again using RMSE, to UNAIDS data from >1,300 untreated, HIV-infected African children. ResultsIn internal validation analyses, model-generated survival curves fit IeDEA data well; modeled and observed survival at 16 months of age were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4% parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4% was 45% at birth and declined by 6%/month (ages 0-3 months) and 0.3%/month (ages >3 months). In calibration analyses, increases in IeDEA-derived mortality risks were necessary to fit UNAIDS survival data. ConclusionsThe CEPAC-Pediatric model performed well in internal validation analyses. Increases in modeled mortality risks required to match UNAIDS data highlight the importance of pre-enrollment mortality in many pediatric cohort studies.

BackgroundWe examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART).MethodsWe used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY.ResultsFor patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving.ConclusionsDepending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.

BackgroundRoutine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.MethodsWe employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.ResultsEstimated HIV screening costs in the provider and counselor arms averaged $8.10 and $31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of $64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.ConclusionsThe cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services.