Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy.

BACKGROUND: Risk factors for acquired rifampicin resistance (ARR) in human immunodeficiency virus (HIV)/tuberculosis coinfection, in the highly active antiretroviral therapy (HAART) era, needs evaluation. We studied the impact of HIV and HAART on ARR among patients taking thrice-weekly antituberculosis therapy. METHODS: This cross-protocol analysis included patients with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis, with and without HIV, enrolled in clinical trials (who took >80% of medication) at the National Institute for Research in Tuberculosis between 1999 and 2013. All patients received rifampicin and isoniazid for 6 months reinforced with pyrazinamide and ethambutol in the first 2 months, given thrice-weekly throughout the study along with HAART in one of the groups. Outcomes were categorized and multivariate logistic regression analysis performed to identify risk factors for ARR. RESULTS: The per-protocol results included patients with tuberculosis: 246 HIV-uninfected patients (HIV(-)TB(+)), 212 HIV patients not on HAART (non-HAART), and 116 HIV-infected patients on HAART. Median CD4 counts of the latter 2 groups were 150 and 93 cells/µL, respectively, and the median viral loads were 147 000 and 266 000 copies/mL, respectively. Compared with HIV(-)TB(+), the relative risks (RRs) for an unfavorable response in the coinfected, non-HAART and HAART groups were 2.1 (95% confidence interval [CI], 1.7-14.8; P<.0001) and 2.1 (95% CI, .9-5.2; P=.3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6-184; P<.001) and 8.2 (95% CI, .6-104; P=.07), respectively. CONCLUSIONS: HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR.

Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIV patients with culture confirmed pulmonary tuberculosis in India and the potential role of IL-6 in prediction.

BACKGROUND: The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. METHODS: HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. RESULTS: Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14-47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7-16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9-23). Two patients died due to CNS TB-IRIS. Lower CD4(+) T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. CONCLUSION: Paradoxical TB-IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions.