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HIV-infected patients commonly use complementary and alternative medicine (CAM), but it is not known how often CAM is used as a complement or as a substitute for conventional HIV therapy.To evaluate the prevalence and factors associated with CAM use with potential for adverse effects and CAM substitution for conventional HIV medication.Cross-sectional survey of U.S. national probability sample of HIV-infected patients (2,466 adults) in care from December 1996 to July 1997.Any CAM use, CAM use with potential for adverse effects, and use of CAM as a substitute for conventional HIV therapy. Substitution was defined as replacement of some or all conventional HIV medications with CAM.Fifty-three percent of patients had recently used at least one type of CAM. One quarter of patients used CAM with the potential for adverse effects, and one-third had not discussed such use with their health care provider. Patients with a greater desire for medical information and involvement in medical decision making and with a negative attitude toward antiretrovirals were more likely to use CAM. Three percent of patients substituted CAM for conventional HIV therapy. They were more likely to desire involvement in medical decision-making (odds ratio, 1.8; 95% confidence interval, 1.0-3.2) and to have a negative attitude toward antiretrovirals (odds ratio, 7.8; 95% confidence interval, 3.0-19.0).Physicians should openly ask HIV-infected patients about CAM use to prevent adverse effects and to identify CAM substitution for conventional HIV therapy.