Opportunistic diseases diminish the clinical benefit of immediate antiretroviral therapy in HIV–tuberculosis co-infected adults with low CD4+ cell counts

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Abstract

Introduction:

HIV–tuberculosis (TB) co-infection remains an important cause of mortality in sub-Saharan Africa. Clinical trials have reported early (within 2 weeks of TB therapy) antiretroviral therapy (ART) reduces mortality among HIV–TB co-infected research participants with low CD4+ cell counts, but this has not been consistently observed. We aimed to evaluate the current WHO recommendations for ART in HIV–TB co-infected patients on mortality in routine clinical settings.

Methods:

We compared two cohorts before (2008–2010) and after (2012–2013) policy change on ART timing after TB and examined the effectiveness of early versus delayed ART on mortality in HIV–TB co-infected participants with CD4+ cell count 100 cells/μl or less. We used inverse probability censoring-weighted Cox models on baseline characteristics to balance the study arms and generated hazard ratios for mortality.

Results:

Of 356 participants with CD4+ cell counts 100 cells/μl or less, 180 were in the delayed ART cohorts whereas 176 were in the early ART cohorts. Their median age (32.5 versus 32 years) and baseline CD4+ cell counts (26.5 versus 26 cells/μl) respectively were similar. There was no difference in mortality rates of both cohorts. The risk of death increased in participants with a positive Cryptococcal antigen (CrAg) test in both the early ART cohort (aHR = 2.6, 95% CI 1.0–6.8; P = 0.045) and the delayed ART cohort (aHR = 4.2, 95% CI 1.9–9.0; P < 0.001

Conclusion:

Early ART in patients with HIV–TB co-infection was not associated with reduced risk of mortality in routine care. Asymptomatic Cryptococcal antigenaemia increased the risk of mortality in both cohorts.

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