Treatment of Active Tuberculosis in HIV-Coinfected Patients

Treatment of Active Tuberculosis in HIV-Coinfected Patients: A Systematic Review and Meta-Analysis.

Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse. A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutin-containing regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta-regression was performed using negative binomial regression. After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1-11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase patients from 35 study arms), thrice-weekly therapy (patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5-10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8-12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with 8 months, or if antiretroviral therapy was not used. This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.

Treatment failure in tuberculosis can be due to true relapse (recurrence of TB with the initial strain) or reinfection (recurrence with a new strain). It is important to distinguish clearly between these two but that requires DNA fingerprinting. It was performed, incompletely, in only 4 of the 27 studies meeting the meta-analysis eligibility criteria. The most striking finding of this analysis is the paucity of adequately powered, well-designed, and well-executed randomized controlled trials on treatment of HIV-TB coinfection. With the mortality rate in HIV-infected patients 6 times higher than in HIV-negative patients, it is urgent to investigate strategies to align these. Daily therapy in the intensive phase (first 2 months) and longer duration of rifamycin treatment clearly were associated with lower rates of failure and/or relapse. Although receipt of antiretroviral therapy was associated with nonsignificantly lower rates of failure and relapse, the SAPIT trial makes clear that initiation of antiretroviral treatment should not wait until the end of tuberculosis treatment (see HIV This Week Issue 79).