When to start ART? A replication study of timing of antiretroviral therapy for HIV-1-associated Tuberculosis

In this paper, the research team conducted a replication study of Havlir and others’ 2011 study, “Timing of antiretroviral therapy for HIV-1 infection and tuberculosis.” The original study tackled the issue of optimal timing for ART initiation in HIV-TB co-infected patients by conducting a large multisite trial in 26 countries to determine the impact of earlier ART (within 2 weeks of the initiation of treatment for tuberculosis) on new AIDS-defining illness and death. The original authors find that earlier ART initiation reduces the rate of new AIDS-defining illness and death only for HIV positive TB patients with a CD4 count lower than 50.

In this replication study, the researcher team conducted a pure replication and measurement and estimation analyses. In general, the pure replication confirmed the main findings of the original paper. In addition, the research team found that earlier ART initiation is associated with a sharp increase in the incidence of TB-associated immune reconstitution inflammatory syndrome (IRIS). Furthermore, using mainly econometric approaches to increase the statistical power of the study and to estimate the treatment effect on patients who actually received earlier ART. The research team find that earlier ART initiation do not reduce the rate of new AIDS-defining illness and death even for HIV-positive TB patients with CD4 counts lower than 50.

Overall, the results of this replication do not provide strong support that earlier ART initiation reduces the rate of new AIDS-defining illness and death only for HIV-positive TB patients with CD4 counts lower than 50.