The effects of cigarette smoking, treated tuberculosis, and isoniazid prophylaxis therapy on HIV disease progression and mortality.

摘要

HIV/AIDS is one of the most devastating scourges in human history, whose full impact is yet to be realized. By 2008, there were 33 million people living with HIV worldwide and 25 million AIDS-associated deaths. Sub-Saharan Africa is the most affected region carrying two-third of all global HIV/AIDS cases. The introduction of Highly Active Antiretroviral Therapy (HAART) in the mid 1990s revolutionizes the treatment for HIV/AIDS worldwide. With this major prognostic advance, interest to identify other potential areas to prevent HIV disease progression has developed. Cigarette smoking is more common among HIV-infected persons than in the general population. Its effect on HIV disease progression is a subject still under active research. Meanwhile, tuberculosis (TB) remains the major underlying cause of death in areas with the high burden of HIV/AIDS. The studies described in this dissertation assessed the role of cigarette smoking, treated TB and Isoniazid (INH) prophylaxis therapy on HIV disease progression and/or all-cause mortality.;The first study analyzed the effect of recent cigarette smoking on CD4' T cell count (CD4 count) and HIV viral load in two cohorts of HIV-infected persons with history of alcohol problems in Massachusetts, United States in the periods 1997-2001 and 2001-2006. After adjusting for confounders, the study did not find substantial changes in CD4 count or viral load associated with smoking. Using non-smokers as the reference group, the adjusted mean differences in CD4 count were: 8.19 (95% confidence interval (CI) -17.39, 33.77) for heavy smokers; -0.14 (95% CI -25.39, 5.10) for moderate smokers; and -2.64 (95% CI -28.29, 3.01) for light smokers. For viral load (measured as log10 plasma HIV RNA), the adjusted differences were: 0.03 (95% CI -0.12, 0.17) for heavy smokers; -0.06 (95% CI -0.20, 0.08) for moderate smokers; and 0.14 (95% CI -0.01, 0.28) for light smokers.;The second study examined whether HIV-infected patients who completed treatment for the first diagnosis of active TB had a higher mortality compared with HIV-infected patients who did not have a history of active TB, using a cohort of HIV-positive adults enrolled in a randomized trial for a TB vaccine in Tanzania. The study found a 2-fold increase in mortality among HIV-infected patients who completed treatment for active TB compared with HIV-infected patients who did not have a history of active TB (relative hazard (RH) = 2.36; 95% Confidence Interval (CI) 1.17, 4.74), but the mean change in CD4 count between the two groups was similar (mean differences = 7.24 cells/mL; 95% CI -10.27, 24.75).;The third study investigated the effectiveness of INH prophylaxis therapy on all-cause mortality and on the incidence of active TB among HIV-infected adults enrolled in a randomized trial of a TB vaccine in Tanzania. HIV-infected patients who completed a 6-months course of INH treatment had a 60% decrease in mortality compared with HIV-infected patients who did not complete 6 months of INH treatment (RH = 0.40; 95% CI: 0.22, 0.73). The incidence of active TB between the two groups was not substantially different (RH 1.23; 95% CI: 0.38, 4.00).