High risk of rifampicin resistance with HIV in 3-group Indian study
HIV-positive people not taking antiretroviral therapy (ART) had a 21 times higher risk of acquiring resistance to rifampicin than did HIV-negative people taking the same anti-TB regimen in an Indian study. Taking ART lowered but did not eliminate the increased resistance risk.
Resistance to rifampicin, a key first-line anti-TB agent, is a dangerous step on the road to multidrug-resistant TB. Because the impact of HIV infection and ART on emergence of resistance to rifampicin remains poorly understood, researchers working with India’s National Institute for Research in Tuberculosis conducted a three-way comparison.
This cross-sectional study involved people with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis. All study participants were enrolled in one of four clinical trials between 1999 and 2013 at the National Institute for Research in Tuberculosis in Chennai. All took more than 80% of their medications.
For 2 months, study participants took rifampicin plus isoniazid, pyrazinamide, and ethambutol three times weekly. They continued rifampicin and isoniazid for another 4 months. Antiretroviral-treated people were taking efavirenz-based regimens.
The study involved 246 HIV-negative people with TB, 212 HIV-positive people not taking ART, and 116 HIV-positive people taking ART. Median initial CD4 counts in the no-ART and ART groups were 150 and 93 cells/µL, and respective viral loads were 147,000 and 266,000 copies/mL.
Compared with HIV-negative TB patients, the no-ART group had a doubled risk of TB treatment failure (relative risk [RR] 2.1, 95% confidence interval 1.7 to 14.8, P < 0.0001). The ART group also had a doubled risk of TB treatment failure, but the difference from the HIV-negative group was not statistically significant (RR 2.1, 95% CI 0.9 to 5.2, P = 0.3).
Compared with HIV-negative patients, the no-ART HIV group had a 21 times higher risk of acquiring rifampicin resistance (RR 21.1, 95% CI 2.6 to 184, P < 0.001). The ART group had an 8 times higher risk of acquiring rifampicin resistance, although that difference fell short of statistical significance (RR 8.2, 95% CI 0.6 to 104, P = 0.07). Rifampicin resistance risk was higher in people who already had resistance to isoniazid when treatment began.
The researchers suggest that “the advanced stage of HIV in the HIV+TB+HAART group (higher viral load and lower CD4 count), with possibly prolonged period of immunodeficiency, could explain why HAART initiation did not completely offset the tendency for emergence of acquired rifampicin resistance, even though it significantly improved overall tuberculosis outcomes.”
The investigators propose that “daily tuberculosis treatment, prompt diagnosis of HIV, and earlier HAART initiation preserving immune function in HIV-infected tuberculosis patients could potentially prevent amplification of drug resistance.”
Source: Gopalan Narendran, Pradeep Aravindan Menon, Perumal Venkatesan, Krishnamoorthy Vijay, Chandrasekaran Padmapriyadarsini, Santhanakrishnan Ramesh Kumar, Kannabiran Perumal Bhavani, Lakshmanan Sekar, Sivaramakrishnan Narayan Gomathi, Chockalingam Chandrasekhar, Satagopan Kumar, Rathinam Sridhar, Soumya Swaminathan, Gopalan Narendran, Pradeep Aravindan Menon, Perumal Venkatesan, Krishnamoorthy Vijay, Chandrasekaran Padmapriyadarsini, Santhanakrishnan Ramesh Kumar, Kannabiran Perumal Bhavani, Lakshmanan Sekar, Sivaramakrishnan Narayan Gomathi, Chockalingam Chandrasekhar, Satagopan Kumar, Rathinam Sridhar, Soumya Swaminathan. Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy. Clinical Infectious Diseases. 2014; 59: 1798-1804.
Source: IAS
