Background
For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events.
Methods
In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12βweeks of starting ATT, and were followed for 12βmonths after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART.
Findings
A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4βweeks (early ART) and 62 after 8-12βweeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (pβ=β0.045). Kaplan Meier disease progression free survival at 12βmonths was 79% for early versus 64% for the delayed ART arm (pβ=β0.05). Rates of adverse events were similar.
Interpretation
Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability.
Trial registration
CTRI/2011/12/002260