Optimal Time to Initiate Antiretroviral Therapy After Pulmonary Tuberculosis Treatment in Pediatric Patients

These study findings support the World Health Organization’s recommendation to initiate antiretroviral therapy in HIV-positive pediatric patients within 2 weeks of initiating treatment for pulmonary tuberculosis.

The initiation of antiretroviral therapy (ART) less than 2 weeks after initiating treatment for pulmonary tuberculosis (TB) infection does not increase the risk of mortality in ART-naive pediatric patients with HIV infection, according to study findings published in Clinical Infectious Diseases.

Researchers conducted a retrospective study to assess the risk of mortality associated with the timing of ART initiation in in children and adolescents (age range, 0-19 years) with HIV-associated pulmonary TB infection. Data were obtained from electronic medical records, and all included patients were naive to ART. The primary outcome was all-cause mortality.

A total of 774 patients were included in the analysis and divided into 4 groups on the basis ART initiation time following pulmonary TB treatment initiation. The 4 groups included patients who initiated ART either never (n=44; group 1), within 2 weeks (n=266; group 2), between 2 weeks and 2 months (n=398; group 3), or more than 2 months (n=66; group 4) after initiating treatment for pulmonary TB infection.

This retrospective study demonstrated no increase in mortality among CALHIV initiating ART less than two-weeks from TB treatment initiation.

The researchers used Cox proportional hazards regression models to assess the results, with adjustments for patient age, BMI z-score, geographic location, time period of pulmonary TB treatment initiation, certainty of TB diagnosis, and CD4+ cell counts. The interval between pulmonary TB treatment initiation and ART initiation was included in the analysis as a time-dependent variable.

The adjusted analysis comprised 71% of the total patient population and 2178 years of follow-up time. At 1 year, the risk of mortality was significantly increased among patients in group 1 (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.03-6.94) compared with those in group 3. Further analysis showed that the risk of mortality did not significantly differ between patients in group 2 (aHR, 1.02; 95% CI, 0.55-1.89) vs those in group 3.

Study limitations include missing data, residual confounding, potential survival bias, and changes in health policy during the study period that may have altered the recommended time of ART initiation.

According to the researchers, “This retrospective study demonstrated no increase in mortality among CALHIV [children and adolescents living with HIV] initiating ART less than two-weeks from TB treatment initiation.

References:

Kay A, Reyes JM, Devezin T, et al. Optimal timing of antiretroviral therapy initiation in children and adolescents with HIV-associated pulmonary tuberculosis. Clin Infect Dis. Published online September 13, 2022. doi:10.1093/cid/ciac765