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Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection

Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection

Antiretroviral therapy for the prevention of HIV-1 transmission

HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy

Review of the Efficacy, Safety, and Pharmacokinetics of Raltegravir in Pregnancy

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals

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Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial

Feasibility and efficacy of early lung cancer diagnosis with chest computed tomography in HIV-infected smokers

Patterns of Cardiovascular Mortality for HIV-Infected Adults in the United States: 1999 to 2013

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis

Outcomes of HIV-associated Hodgkin lymphoma in the era of antiretroviral therapy

CD4+ and CD8+ T-cell kinetics in aviremic HIV-infected patients developing Hodgkin or non-Hodgkin lymphoma

CD8 T-Cell Expansion and Inflammation Linked to CMV Coinfection in ART-treated HIV Infection

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Ongoing HIV Replication Replenishes Viral Reservoirs During Therapy

Incidence and progression of coronary artery calcium in HIV-infected and HIV-uninfected men

Transient elastography for the detection of hepatic fibrosis in HIV-monoinfected adults with elevated aminotransferases on antiretroviral therapy

Association of immune-activation and senescence markers with non-AIDS-defining comorbidities in HIV-suppressed patients

Effects of randomized rosuvastatin compared with placebo on bone and body composition among HIV-infected adults

Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy

Cancer Risk and Use of Protease Inhibitor or Nonnucleoside Reverse Transcriptase Inhibitor–Based Combination Antiretroviral Therapy The D:A:D Study

Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study

TEMPRANO

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The effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study

Course and Clinical Significance of CD8+ T-Cell Counts in a Large Cohort of HIV-Infected Individuals

Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients

HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007-12: impact on susceptibility to first-line strategies

Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals

Cross-sectional Comparison of the Prevalence of Age-Associated Comorbidities and Their Risk Factors Between HIV-Infected and Uninfected Individuals: The AGEhIV Cohort Study

CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study

Baseline HIV-1 resistance, virological outcomes, and emergent resistance in the SECOND-LINE trial: an exploratory analysis

Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial

Low Bone Mineral Density in Patients With Well-Suppressed HIV Infection: Association With Body Weight, Smoking, and Prior Advanced HIV Disease

Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial

A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans

Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial

Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1

TEMPRANO
Published by Anton POZNAK

Updated: 1 October, 2015

The TEMPRANO ANRS 12136 Study Group et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22.

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.