Temprano was a factorial 2×2 trial that assessed the benefits of early antiretroviral therapy (ART) and 6-month isoniazid prophylaxis (IPT) among HIV-infected adults in Côte d’Ivoire. Participants were randomly assigned to four groups (deferred-ART- No-IPT, deferred-ART-plus-IPT, early-ART-No-IPT, early ART-IPT). Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here we present the efficacy of IPT in reducing mortality in the long term.
Participants who completed the trial follow up were invited to participate in a post trial phase (PTP). The PTP endpoint was death in an intention-to-treat analysis. We used Cox proportional models to compare mortality between the IPT and No-IPT strategies from inclusion in Temprano to January 2015.
2,056 patients (mean baseline CD4 count 477/mm3) were followed for 9,404 patient-years (Temprano 4,757; PTP 4,647). A total of 86 deaths were observed (Temprano 47; PTP 39), 34 in patients randomized to IPT (six-year probability 4.1%, 95% CI 2.9 to 5.7) and 52 in those randomized to No-IPT (six-year probability 6.9%, 95% CI 5.1 to 9.2). The hazard ratio of death for IPT compared to No-IPT was 0.63 (95% CI, 0.41 to 0.97) after adjusting for the ART strategy (Early vs. Deferred), and 0.61 (95% CI, 0.39 to 0.94) after adjusting for the ART strategy, baseline CD4 count and other key factors.
In these African HIV-infected adults with high CD4 counts, 6-month IPT led to a 39% decrease in mortality, independently of ART initiation and baseline CD4 count.