A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

Abstract

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (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 per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (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). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Comparative assessment of five trials of universal HIV testing and treatment in sub‐Saharan Africa

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The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu‐Natal (South Africa)

“…Early antiretroviral treatment (ART) of HIV‐positive patients has been shown to prevent transmission of HIV 1, in addition to individual benefits in terms of reducing morbidity and mortality 2, 3. The universal test and treat (UTT) strategy was developed by extending this idea to the population level under the hypothesis that HIV testing of all adult members of a community, followed by immediate ART initiation of nearly all HIV‐positive individuals, regardless of immunological or clinical staging, will prevent onward transmission and reduce HIV incidence in the community.…”

Do HIV treatment eligibility expansions crowd out the sickest? Evidence from rural South Africa

“…This recommendation reversed earlier guidelines that limited treatment to patients with lower CD4 counts or severe illness 1. Although expanding eligibility is expected to reduce morbidity, mortality and transmission among patients with high CD4 2, 3, 4, 5, 6, 7, 8, it is possible that a large influx of newly eligible patients in a resource‐limited health system could crowd out sicker patients and reduce quality of care for all patients. As of September 2016, South Africa has joined three other countries in sub‐Saharan Africa in adopting the WHO ‘test‐and‐treat’ policy 9, 10, and additional resource‐limited countries are also considering expanding eligibility 11, 12.…”