Search

Rochelle Walensky and colleagues use a model-based analysis to examine which of the 2010 WHO antiretroviral therapy guidelines should be implemented first in resource-limited settings by ranking them according to survival, cost-effectiveness, and equity., Background The new 2010 World Health Organization (WHO) HIV treatment guidelines recommend earlier antiretroviral therapy (ART) initiation (CD4, Editors' Summary Background Since 1981, acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people, and about 33 million people (30 million of them in low- and middle-income countries) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections (so-called opportunistic infections). Early in the AIDS epidemic, most people with HIV died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART)—a combination of several powerful antiretroviral drugs—was developed. Now, in resource-rich countries, clinicians care for people with HIV by prescribing ART regimens tailored to each individual's needs. They also regularly measure the amount of virus in their patients' blood, test for antiretroviral-resistant viruses, and monitor the health of their patients' immune systems through regular CD4 cell counts. As a result, the life expectancy of patients with HIV in developed countries has dramatically improved. Why Was This Study Done? Initially, resource-limited countries could not afford to provide ART for their populations, and the life expectancy of HIV-positive people remained low. Now, through the concerted efforts of governments, the World Health Organization (WHO), and other international agencies, more than a third of the people in low- and middle-income countries who need ART are receiving it. However, many without access are still in need of ART, and ART programs in developing countries follow a public-health approach rather than an individualized approach. That is, drug regimens, clinical decision-making, and disease monitoring are all standardized and follow recommendations in the 2006 WHO ART guidelines. This year (2010), these guidelines were revised. The guidelines now recommend the following: earlier ART initiation—when the CD4 count falls below 350/µl of blood, instead of below 200/µl as in the 2006 guidelines; the provision of sequential ART regimens instead of a single regimen; and the replacement of the antiretroviral drug stavudine with tenofovir, a less toxic but more expensive drug, in first-line ART regimens. However, many resource-limited countries are still struggling to implement the 2006 guidelines, so which of these new recommendations should be prioritized? Here, the researchers use a mathematical model to address this question. What Did the Researchers Do and Find? The Cost Effectiveness of AIDS Complications (CEPAC)–International model simulates the natural history and treatment of HIV disease. The researchers entered South African clinical and cost data for HIV treatment into this model and then used it to project survival and costs in a hypothetical group of South African HIV-positive patients under alternative guideline prioritization scenarios. The reference strategy for the simulations (denoted as “stavudine/WHO/one-line”) assumed that patients (with a mean CD4 count of 375/µl) began a single stavudine-based ART regimen when they developed WHO stage III/IV HIV disease (i.e., when patients develop multiple opportunistic infections such as tuberculosis and pneumonia). When the new guideline recommendations were considered separately, ART initiation at CD4