Treatment of active tuberculosis in HIV-coinfected patients: A systematic review and meta-analysis.

Rationale: Patients with HIV-related tuberculosis (TB) have an increased risk of death, TB treatment failure, and relapse. There are several areas of uncertainty regarding the treatment of active TB in this situation including the ideal duration of rifamycin, the effect of dosing schedule, and the effect of antiretroviral therapy (ART). Methods: A systematic review and meta-analysis of randomized controlled trials and cohort studies addressing treatment of active TB in HIV-positive patients. Studies were included if the initial TB 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. Results: We searched Embase, Medline, and the Cochrane Central Register of Controlled Trials. After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens utilizing 2 months rifamycin [adjusted incidence rate ratios: 3.6 (95% confidence interval: 1.1, 11.7)], than with regimens utilizing rifamycin for at least 8 months. Compared to daily therapy in the initial phase, thrice weekly therapy initially was associated with higher rates of failure [aIRR: 4.0 (1.15, 10.4)] and relapse [aIRR: 4.8 (1.8, 12.8)]. There were trends toward higher relapse rates if rifamycins were used for only six months compared to eight months or more [aIRR: 2.4 (0.8, 7.4)], or if antiretroviral therapy was not used [aIRR: 3.5 (0.5, 26)]. (Table Presented) *Estimates of Incidence Rate Ratios (aIRR), derived from multivariate negative binomial regression. Estimates shown from final models which included these three factors, as well as age and proportion with initial drug resistance (any form). Duration of follow-up after treatment not significantly associated with relapse, while directly observed treatment, and percent drop-out (includes protocol violations, patient refusal or default, or not accounted for) – not significantly associated with any outcome. Therefore estimates for these covariates are not shown as they were not included in final models. + Significance in model from likelihood ratio test. Conclusion: This review raises serious concerns regarding the optimal duration and dosing schedule for the treatment of active TB in HIV-positive patients. These concerns cannot be properly addressed with the available evidence. The data suggest that longer duration of rifamycin therapy (at least 8 months) with daily dosing, with concurrent ART might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.

• Population(s)
  • General HIV+ population
• Engagement and Care Cascade
  • Treatment
• Co-infections
  • Tuberculosis