Background: We present the final results of the Temprano ANRS 12136 trial that assessed the benefits of early ART and/or early 6-month isoniazid prophylaxis (IPT, 300 mg/day) among HIV-infected adults with high CD4 counts and no WHO criteria for starting ART.
Methods: Temprano was a randomized 2×2 factorial superiority trial conducted in 9 HIV care centers in Côte d’Ivoire from March 2008 through January 2015. Inclusion criteria were: HIV-1 infection, age >18 years, CD4 nadir <800/ul, and no criteria for starting ART according to the most recent WHO guidelines. Participants were randomized to one of four arms: ART initiation according to WHO criteria (WHOART); immediate 6-month IPT plus ART initiation according to WHO criteria (WHOART-IPT); immediate ART initiation (EarlyART); immediate 6-month IPT plus immediate ART initiation (EarlyART-IPT). First-line ART consisted of tenofovir plus emtricitabine plus either efavirenz, zidovudine or lopinavir/ritonavir. The primary endpoint was severe HIV morbidity (AIDS-defining diseases, non-AIDS-defining malignancy, or non-AIDS-defining invasive bacterial diseases),or any-cause mortality at 30 months. The secondary endpoint was any other grade 3-4 defining morbidity. We used multivariate Cox proportional models to compare outcomes between the WHOART and EarlyART arms, and between the IPT and no IPT arms. We tested for interaction between earlyART and IPT.
Results: Of 2,076 patients randomized, 2,056 were included in the analysis (78% were women; 91% classified at WHO stage 1-2; median age 35 years; median CD4 nadir 465/ul; median HIV-1 viral load 4.7 log10 copies/ml). They were followed for 4,755 patient-years, during which 47 died, 175 experienced 204 episodes of severe morbidity (TB 85, invasive bacterial diseases 56, other AIDS-defining diseases 11, non-AIDS malignancy 5), 287 experienced 364 episodes of severe grade 3-4 morbidity (hematologic 256, hepatic 31 renal, 22, cardiovascular 9, others 46), and 44 (2.2%) were lost-to-follow up. There was no interaction between EarlyART and IPT. The risk of severe morbidity was 44% lower with EarlyART vs. WHOART (Table) and 35% lower with IPT vs. no IPT. EarlyART significantly decreased morbidity overall and when restricted to patients with baseline CD4 >500/ul. The risk of Grade 3-4 morbidity did not differ between strategies.
Conclusions: In Côte d’Ivoire, both immediate ART and IPT dramatically and independently decreased the risk of severe morbidity, and should be recommended as the standard of care for HIV.