Patients with HIV and tuberculosis were more likely to develop acquired rifampicin resistance when treated with a thrice-weekly tuberculosis treatment compared with patients not coinfected with HIV, according to researchers from the National Institute for Research in Tuberculosis in India.
“[Antiretroviral therapy] reduces but does not eliminate the risk of [acquired rifampicin resistance] completely,” the researchers wrote in Clinical Infectious Diseases. “Daily TB treatment, prompt diagnosis of HIV and earlier [ART] initiation preserving immune function in HIV-infected TB patients, could potentially prevent amplification of drug resistance.”
The retrospective cross-protocol analysis included patients with newly diagnosed pulmonary TB who were enrolled in randomized clinical trials. The patients included 246 without HIV, 212 with HIV but not receiving ART and 116 patients with HIV and receiving ART. All of the patients had rifampicin-susceptible TB at baseline and received a TB treatment regimen that included thrice-weekly isoniazid and rifampicin for 6 months, with ethambutol and pyrazinamide in the first 2 months of therapy.
The rate of bacteriologic failure was 4% among patients without HIV. Among patients with HIV, the rates were 9% for those not receiving ART and 5% for those receiving ART. Patients with HIV were more likely to have an unfavorable response to treatment compared with patients without HIV (RR=5.1; 95% CI, 1.7-14.8). Among patients with HIV, the risk was 2.4 times more among those not receiving ART (95% CI, 1.2-4.7).
The 19 patients with HIV but not receiving ART who failed therapy all developed acquired rifampicin resistance. Three patients with HIV and receiving ART who failed therapy also developed acquired rifampicin resistance, as did one patient in the group of HIV-negative patients who failed therapy. For patients with HIV but not receiving ART, the relative risk of acquired rifampicin resistance was 21.1 (95% CI, 2.6-184) compared with HIV-negative patients. The relative risk was 8.2 (95% CI, 0.6-104) among patients with HIV receiving ART. Among patients with HIV, the risk for acquired rifampicin resistance was 2.6 more (95% CI, 0.9-7.4) among patients not receiving ART.
In a multiple logistic regression analysis, the researchers found that baseline isoniazid resistance and HIV were risk factors for acquired rifampicin resistance. Among patients with HIV, isoniazid resistance was a significant risk factor, as were lower CD4 count and higher sputum culture grade at baseline.
“The advanced stage of HIV in the [patients with HIV receiving ART], with possibly prolong period of immunodeficiency, could explain why [ART] initiation did not completely offset the tendency for emergence of acquired rifampicin resistance, even though it significantly improved overall TB outcomes,” the researchers wrote. “Hence, the WHO recommendation for early and concomitant initiation of [ART] for all [patients with HIV and TB], irrespective of CD4 counts, while reducing failures, may not fully protect against emergence of acquired rifampicin resistance.”
Disclosure: The researchers report no relevant financial disclosures.