Background The combination of tenofovir and emtricitabine (TDF/FTC) shows promise as HIV pre-exposure prophylaxis (PrEP). We sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, risk of resistance and toxicity, behavioral disinhibition, and drug costs. Methods We adapted a computer simulation of HIV acquisition, detection, and care to model PrEP in high-risk (1.6% average annual HIV incidence) men who have sex with men (MSM) in the United States. Base case assumptions included: 50% PrEP efficacy and $753 monthly TDF/FTC costs. We used sensitivity analyses to examine the stability of results and to identify critical input parameters. Results In a cohort with mean age 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased average life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted, quality-adjusted life-years or QALYs). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio (ICER) of $298,000 per QALY gained. Markedly larger reductions in lifetime infection risk (from 43.5% to 5.8%) were observed assuming greater (90%) PrEP efficacy. More favorable ICERs were obtained by targeting younger, higher-incidence populations and with improvements in the efficacy and cost of PrEP. Conclusions PrEP could substantially reduce HIV transmission in high-risk populations in the United States. Although it is unlikely to confer sufficient benefits to justify current TDF/FTC costs, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger or higher-risk populations. Given recent disappointments in HIV prevention and vaccine development, further study of PrEP-based HIV prevention is warranted.

BackgroundAlthough loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa.Methodology/Principal FindingsWe assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived ≥10 kilometers from the testing center (RR = 1.37; 95% CI: 1.11–1.71), had a history of tuberculosis treatment (RR = 1.26; 95% CI: 1.00–1.58), or were referred for testing by a health care provider rather than self-referred (RR = 1.61; 95% CI: 1.22–2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors.Conclusions/SignificanceNearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.

Objective To evaluate the clinical impact and cost-effectiveness of HLA-B*5701 testing to guide selection of first-line HIV regimens in the United States. Design Cost-effectiveness analysis using a simulation model of HIV disease. The prevalence of HLA-B*5701 and the probabilities of confirmed and unconfirmed severe systemic hypersensitivity reaction (HSR) among patients taking abacavir testing HLA-B*5701 positive and negative were from the PREDICT-1 trial. The monthly costs of abacavir and tenofovir-based regimens were $1,135 and $1,139; similar virologic efficacy was assumed and this assumption was varied in sensitivity analysis. Subjects Simulated cohort of patients initiating HIV therapy. Interventions 1) first-line abacavir, lamivudine, and efavirenz without pre-treatment HLA-B*5701 testing; 2) the same regimen with HLA-B*5701 testing; 3) first-line tenofovir, emtricitabine, and efavirenz. Main Outcome Measures Quality-adjusted life expectancy (QALYs) and lifetime medical costs discounted at 3% p.a., cost-effectiveness ratios ($/QALY). Results Abacavir-based treatment without HLA-B*5701 testing resulted in a projected 30.93 years life expectancy, 16.23 discounted QALYs, and $472,200 discounted lifetime cost per person. HLA-B*5701 testing added 0.04 quality-adjusted months at an incremental cost of $110, resulting in a cost-effectiveness ratio of $36,700/QALY compared to no testing. Initiating treatment with a tenofovir-based regimen increased costs without improving QALYs. HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA*B5701. Conclusions Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment.

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.