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Kenneth A. Freedberg, MD, MSc; Julie A. Scharfstein, MS, ScD; George R. Seage III, DSc, MPH; Elena Losina, MS; Milton C. Weinstein, PhD; Donald E. Craven, MD; A. David Paltiel, PhD

JAMA. 1998;279:130-136.

Context.— Multiple options are now available for prophylaxis of opportunistic infections related to the acquired immunodeficiency syndrome (AIDS). However, because of differences in incidence rates as well as drug efficacy, toxicity, and costs, the role of different types of prophylaxis remains uncertain.

Objective.— To determine the clinical impact, cost, and cost-effectiveness of strategies for preventing opportunistic infections in patients with advanced human immunodeficiency virus (HIV) disease.

Design.— We developed a Markov simulation model to compare different strategies for prophylaxis of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) infection, fungal infections, and cytomegalovirus (CMV) disease in HIV-infected patients. Data for the model were derived from the Multicenter AIDS Cohort Study, randomized controlled trials, and the national AIDS Cost and Services Utilization Survey.

Main Outcome Measures.— Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) saved.

Results.— For patients with CD4 cell counts of 0.200 to 0.300x10⁹/L (200-300/µL) who receive no prophylaxis, we projected a quality-adjusted life expectancy of 39.08 months and average total lifetime costs of $40288. Prophylaxis for PCP and toxoplasmosis with trimethoprim-sulfamethoxazole for patients with CD4 cell counts of 0.200x10⁹/L (200/µL) or less increased quality-adjusted life expectancy to 42.56 months, implying an incremental cost of $16000 per QALY saved. Prophylaxis for MAC for patients with CD4 cell counts of 0.050x10⁹/L (50/µL) or less produced smaller gains in quality-adjusted life expectancy; incremental cost-effectiveness ratios were $35000 per QALY saved for azithromycin and $74000 per QALY saved for rifabutin. Oral ganciclovir for the prevention of CMV infection was the least cost-effective prophylaxis ($314000 per QALY saved). Results were most sensitive to the risk of developing an opportunistic infection, the impact of opportunistic infection history on long-term survival, and the cost of prophylaxis.

Conclusions.— The cost-effectiveness of prophylaxis against HIV-related opportunistic infections varies widely, but prophylaxis against PCP or toxoplasmosis and against MAC delivers the greatest comparative value. In an era of limited resources, these results can be used to set priorities and explore new alternatives for improving HIV patient care.

From the Clinical Economics Research Unit (Drs Freedberg and Scharfstein), Section of General Internal Medicine and the Clinical AIDS Program (Drs Freedberg and Craven), Department of Medicine and Evans Medical Foundation, Boston Medical Center; the Department of Epidemiology and Biostatistics (Drs Freedberg, Seage, and Craven and Ms Losina), Boston University School of Public Health, Boston University School of Medicine, Boston, Mass; the Departments of Health Policy and Management (Drs Freedberg and Weinstein) and Biostatistics (Drs Scharfstein and Weinstein), Harvard School of Public Health, Boston; and the Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn (Dr Paltiel).

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