In patients with HIV and multidrug-resistant tuberculosis, the use of antiretroviral therapy (ART) and more effective anti-tuberculosis drugs was associated with lower odds of death, according to the results of a study published in the Lancet.
Patients with HIV infection and receiving treatment for multidrug-resistant tuberculosis treatment are at increased risk for mortality, but the extent to which ART and tuberculosis medications affect this risk is not clear. Investigators therefore aimed to evaluate how these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis.
To do so, they employed an individual patient data meta-analysis of 11,920 adults aged ≥18 years with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between the years 1993 and 2016. Of these patients, 25% were HIV-positive and receiving ART, 7% were HIV-positive and not receiving ART, and 15% had extensively drug-resistant tuberculosis. By using the HIV-negative patients as a reference, the adjusted odds ratio of death was found to be 2.4 (95% CI, 2.0-2.9) for all patients with HIV infection, 1.8 (95% CI, 1.5-2.2) for HIV-positive patients receiving ART, and 4.2 (95% CI, 3.0-5.9) for HIV-positive patients with no or unknown ART. For those patients with HIV, the use of at least one World Health Organization Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death.
The investigators noted several limitations of their research, including the fact that 17% of patients were lost to follow-up. Although these patients were similar to those who were not lost to follow-up in terms of most clinical and treatment characteristics, the investigators report that “differential rates of death among patients with HIV after becoming lost could have introduced bias into our results.” Data on CD4 counts, ART regimen types, timing of ART initiation, treatment adherence, and precise time of disease onset were also unavailable; therefore, variability in these factors could not be analyzed and residual confounding in HIV-specific analyses might also be present. Missing data represents another limitation, but the investigators did employ a multiple imputation approach that reduces bias compared with complete case analysis. The study was also not designed to examine changes in the association between HIV and mortality over time, and children were excluded. Furthermore, inclusion of data was dependent on investigators’ willingness to participate, most of the data for HIV-positive patients came from South Africa, and studies published since the dataset was assembled were not included; hence, the results may not be generalizable to all settings.
According to the investigators, this study does indicate that ART and high-quality anti-tuberculosis drugs reduce deaths due to multidrug-resistant tuberculosis in adults living with HIV. They added that “a substantial proportion of deaths in patients with HIV occur early after initiation of treatment for multidrug-resistant tuberculosis, and odds of these early deaths are reduced by use of ART and Group A tuberculosis medications.”
Bisson GP, Bastos M, Campbell JR, et al. Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis. Lancet. 2020;396:402-411.