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CDC HIV/AIDS/Viral Hepatitis/STD/TB Prevention News Update
CAMBODIA: Earlier Versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis
Francois-Xavier Blanc, MD, PhD; Thim Sok, MD; and others
October 31, 2011
New England Journal of Medicine Vol. 365; No. 16: P. 1471-1481

TB continues to be an important cause of mortality among HIV patients. However, robust data are lacking with respect to the time of initiating antiretroviral therapy (ART) in relation to the start of TB therapy, noted the authors of the current study.

The researchers tested the hypothesis that the timing of ART initiation would significantly affect mortality among ART- naive HIV patients newly diagnosed with TB whose CD4+ T-cell counts were 200 per cubic millimeter or lower. At five hospitals in Cambodia, patients began a six-month course of TB treatment and were randomly assigned to either earlier ART (two weeks after TB treatment initiation) or later ART (eight weeks after TB treatment began). The ART regimen was stavudine, lamivudine, and efavirenz. Survival was the primary end point.

In total, 661 patients were enrolled and followed for a median of 25 months. The median CD4 count was 25 per cubic millimeter, and median viral load 5.64 log10 copies per milliliter.

The risk of death was significantly reduced in patients receiving ART earlier, with 59 deaths among the 332 (18 percent) earlier-ART patients compared with 90 deaths among the 329 (27 percent) later-ART patients (hazard ratio, 0.62; 95 percent confidence interval; 0.44 to 0.86; P=0.006). The risk of TB-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (HR, 2.51; 95 percent CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5 percent of patients.

"Initiating ART two weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower," concluded the study authors.