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To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic, economically disadvantaged HIV-positive population.A two-group randomized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach.Current smokers from a large, inner city HIV/AIDS care center were recruited and randomized to receive either usual care or a cellular telephone intervention. The usual care group received brief physician advice to quit smoking, targeted self-help written materials and nicotine replacement therapy. The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components. Smoking-related outcomes were assessed at a 3-month follow-up.The trial had 95 participants and 77 (81.0%) completed the 3-month follow-up assessment. Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3% for the usual care group and 36.8% for the cellular telephone group; participants who received the cellular telephone intervention were 3.6 times (95% confidence interval, 1.3-9.9) more likely to quit smoking compared with participants who received usual care (P = 0.0059).These results suggest that individuals living with HIV/AIDS are receptive to, and can be helped by, smoking cessation treatment. In addition, smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS, such as counseling delivered by cellular telephone, can significantly increase smoking abstinence rates over that achieved by usual care.