Date Published: May 3, 2011
Publisher: Public Library of Science
Author(s): Molly F. Franke, James M. Robins, Jules Mugabo, Felix Kaigamba, Lauren E. Cain, Julia G. Fleming, Megan B. Murray, Madhukar Pai
Abstract: Molly Franke, Megan Murray, and colleagues report that early cART reduces
mortality among HIV-infected adults with tuberculosis and improves retention in
care, regardless of CD4 count.
Partial Text: Until recently, there was a paucity of high-quality scientific evidence regarding the
optimal time to initiate combination antiretroviral therapy (cART) in adults with
HIV and tuberculosis (TB) disease. This uncertainty has posed a major challenge for
clinicians, who often defer cART in individuals initiating TB treatment because of
concern about immune reconstitution inflammatory syndrome (IRIS) –, the
possibility of drug interactions  and adverse side effects , and the risk of reduced adherence
due to a higher pill burden among individuals receiving concomitant treatment.
Deferral of cART is not without risk: higher mortality was observed among
HIV-infected TB patients who received cART either late in the course of TB treatment
or not at all –. In recognition of this clinical dilemma, a 2005 World
Health Organization (WHO) expert panel identified the assessment of the optimal time
to initiate cART as the top research priority related to antiretroviral therapy
(ART) for people living with HIV and TB .
We conclude that cART initiation after 15 d of TB treatment is more beneficial on an
absolute scale (measured by differences in survival probabilities) among individuals
with TB who have CD4 cell counts≤100 cells/µl, compared with later
initiation. Early cART may also improve survival, but less so in terms of absolute
risks, for individuals with CD4 cell counts≥200 cells/µl: the difference in
survival probabilities was smaller when CD4 cell counts were set to 200 and 300
cells/µl, and we may have lacked statistical power to detect small
differences. Given that individuals with CD4 cell counts≥200 cells/µl are
eligible for cART in most HIV programs, the higher survival probabilities observed
for individuals with a CD4 cell count of 200 cells/µl who initiated cART by
day 60, although not statistically significant, suggest that there is no reason to
defer cART past 60 d in this group. Early cART may also increase retention in care
for all individuals with CD4 cell counts≤350 cells/µl.