Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study
Background:
Randomized clinical trials examining the optimal time to initiate combination
antiretroviral therapy (cART) in HIV-infected adults with sputum
smear-positive tuberculosis (TB) disease have demonstrated improved survival
among those who initiate cART earlier during TB treatment. Since these
trials incorporated rigorous diagnostic criteria, it is unclear whether
these results are generalizable to the vast majority of HIV-infected
patients with TB, for whom standard diagnostic tools are unavailable. We
aimed to examine whether early cART initiation improved survival among
HIV-infected adults who were diagnosed with TB in a clinical setting.
Methods and Findings:
We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with
a CD4 count≤350 cells/µl and a TB diagnosis. We estimated the
effect of cART on survival using marginal structural models and simulated
2-y survival curves for the cohort under different cART strategies:
start
cART 15, 30, 60, or 180 d after TB treatment or never start cART. We
conducted secondary analyses with composite endpoints of (1) death, default,
or lost to follow-up and (2) death, hospitalization, or serious
opportunistic infection. Early cART initiation led to a survival benefit
that was most marked for individuals with low CD4 counts. For individuals
with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15
yielded 2-y survival probabilities of 0.82 (95% confidence interval:
[0.76, 0.89]) and 0.86 (95% confidence interval:
[0.80, 0.92]), respectively. These were significantly higher than
the probabilities computed under later start times. Results were similar for
the endpoint of death, hospitalization, or serious opportunistic infection.
cART initiation at day 15 versus later times was protective against death,
default, or loss to follow-up, regardless of CD4 count. As with any
observational study, the validity of these findings assumes that biases from
residual confounding by unmeasured factors and from model misspecification
are small.
Conclusions:
Early cART reduced mortality among individuals with low CD4 counts and
improved retention in care, regardless of CD4 count.
: Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study. PLoS Med 8(5): e32767. doi:10.1371/journal.pmed.1001029
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001029
Souhrn
Background:
Randomized clinical trials examining the optimal time to initiate combination
antiretroviral therapy (cART) in HIV-infected adults with sputum
smear-positive tuberculosis (TB) disease have demonstrated improved survival
among those who initiate cART earlier during TB treatment. Since these
trials incorporated rigorous diagnostic criteria, it is unclear whether
these results are generalizable to the vast majority of HIV-infected
patients with TB, for whom standard diagnostic tools are unavailable. We
aimed to examine whether early cART initiation improved survival among
HIV-infected adults who were diagnosed with TB in a clinical setting.
Methods and Findings:
We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with
a CD4 count≤350 cells/µl and a TB diagnosis. We estimated the
effect of cART on survival using marginal structural models and simulated
2-y survival curves for the cohort under different cART strategies:
start
cART 15, 30, 60, or 180 d after TB treatment or never start cART. We
conducted secondary analyses with composite endpoints of (1) death, default,
or lost to follow-up and (2) death, hospitalization, or serious
opportunistic infection. Early cART initiation led to a survival benefit
that was most marked for individuals with low CD4 counts. For individuals
with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15
yielded 2-y survival probabilities of 0.82 (95% confidence interval:
[0.76, 0.89]) and 0.86 (95% confidence interval:
[0.80, 0.92]), respectively. These were significantly higher than
the probabilities computed under later start times. Results were similar for
the endpoint of death, hospitalization, or serious opportunistic infection.
cART initiation at day 15 versus later times was protective against death,
default, or loss to follow-up, regardless of CD4 count. As with any
observational study, the validity of these findings assumes that biases from
residual confounding by unmeasured factors and from model misspecification
are small.
Conclusions:
Early cART reduced mortality among individuals with low CD4 counts and
improved retention in care, regardless of CD4 count.
: Please see later in the article for the Editors' Summary
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