published data using a computer simulation model of HIV disease

When to start antiretroviral therapy in resource-limited settings.

The results of international clinical trials that are assessing when to initiate antiretroviral therapy will not be available for several years. The authors set out to inform HIV treatment decisions about the optimal CD4 threshold at which to initiate antiretroviral therapy in South Africa while awaiting the results of these trials by carrying out cost-effectiveness analysis of published data using a computer simulation model of HIV disease. The data were from randomized trials and observational cohorts in South Africa and the target population was HIV-infected patients in South Africa over a 5-year time horizon and over lifetime. The perspective was modified societal. The interventions considered were: no treatment, antiretroviral therapy initiated at a CD4 count less than 0.250 x 10(9) cells/L, and antiretroviral therapy initiated at a CD4 count less than 0.350 x 10(9) cells/L. The outcome measures were morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved. Initiating antiretroviral therapy at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%. This model does not consider the possible benefits of initiating antiretroviral therapy at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission. Earlier initiation of antiretroviral therapy in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended.