The Temprano trial (ANRS 12136) was conducted in Ivory Coast (Sub-Saharan Africa) were the burden of HIV–associated tuberculosis is high. The trial had a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy, 6-month isoniazid preventive therapy, or both among HIV-infected adults with high CD4+ cell counts. Patients were eligible if they were 18 years of age or older, had HIV-1 or dual HIV-1 and HIV-2, CD4+ count < 800 cells/mm³, without having criteria for starting ART according to the most recent WHO guidelines. There was no chest radiography systematically performed before inclusion. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART + isoniazid preventive therapy, early ART (immediate ART initiation), or early ART + isoniazid preventive therapy. The primary end point was a composite of death of any cause, AIDS defining disease, non–AIDS-defining cancer, or non–AIDS-defining invasive bacterial disease. Patients were followed for 30 months. Cox proportional models were used to compare outcomes between the deferred-ART and early-ART strategies and between the isoniazid preventive therapy and no- isoniazid preventive therapy strategies.

Results: A total of 2,056 patients (41% with a baseline CD4+ count of ≥ 500 cells/mm³, and 38% with the baseline CD4+ count between 350-500 cells/mm³) were followed for 4,757 patient-years. A total of 204 primary end-point events were observed including 68 patients with a baseline CD4+ count > 500 cells/mm³ (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥ 500 cells/mm³, 0.56; 95% CI, 0.33 to 0.94) and was also lower with isoniazid preventive therapy than without isoniazid preventive therapy (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥ 500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). There was no significant interaction among the 2 strategies (ART versus no-ART and IPT vs no-IPT). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the 2 strategies.

In conclusion, in this study conducted in Ivory Coast, ART had a favorable benefit risk ratio in patients before CD4+ count reaches the current treatment threshold of 500 cells/mm³. Early antiretroviral therapy and 6 months of isoniazid preventive therapy independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and in patients with CD4+ counts ≥ 500 cells/mm³. Six months of isoniazid preventive therapy combined with early antiretroviral therapy led to improved outcome. Early antiretroviral therapy had a protective effect including not only tuberculosis but also invasive bacterial disease.