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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

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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

Human Immunodeficiency Virus Infection Does Not Worsen Prognosis of Liver Transplantation for Hepatocellular Carcinoma

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



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

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

Updated: 13 July, 2016

Hosseinipour MC et al. Lancet. 2016 Mar 19;387(10024):1198-209.
Mortality within the first 6 months after initiating ART is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy (IPT) is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. The aim was to assess whether empirical tuberculosis treatment (ETT) would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. A multicountry open-label randomised clinical trial compared ETT with IPT in HIV-positive outpatients initiating ART with CD4 cell counts < 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests ≤ 2-5 times the upper limit of normal, a creatinine clearance > 30 mL/min, and a Karnofsky score > 30. Participants were randomly assigned (1:1) to either ART and ETT or ART and IPT. The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of ART and tuberculosis treatment. This trial is registered with, number NCT01380080. Between Oct 31, 2011, and June 9, 2014, were enrolled 850 participants: 424 were randomised to receive ETT and 426 to the IPT group. The median CD4 cell count at baseline was 18 cells per μL (IQR 9–32). At week 24, 22 (5.2%) participants from each group died or were of unknown status (95% CI 3·5–7·8 for ETT group and 3·4–7·8 for IPT ; absolute risk difference of –0·06% (95% CI –3·05 to 2·94). All primary endpoints were deaths except for 2 unknown vital status events in the ETT. The time to the primary event did not differ between groups. Causes of death included HIV-associated infections (17 in ETT group, 11 in IPT group), non-HIV diagnoses (5 in IPT group), renal toxicity attributed to tenofovir (1 in IPT group), unknown in 6 cases (2 in ETT group, 4 in IPT group), and motor vehicle accident (1 in IPT group). The most common HIV-associated causes of death were cryptococcal meningitis (n=4), Kaposi's sarcoma (n=3), and extrapulmonary tuberculosis (n=3). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the ETT group and 46 (11%) participants in the IPT group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the ETT group and 97 (23%) participants in the IPT group. By week 24, the ETT group had a higher rate of death or AIDS progression than the IPT group (72 [17%] vs 53 [13%]; p=0·06) and the time to death or AIDS progression was more rapid in the ETT group. This result was mainly due to an increased incidence of tuberculosis (31 participants in the ETT group and 18 participants in the IPT group; p=0·01), including both pulmonary and extrapulmonary disease. The time to confirmed or probable tuberculosis in the ETT group was also more rapid. The ETT group also had more premature discontinuations of tuberculosis drugs by week 24 (47 vs 18). A viral load < 400 copies per mL was achieved by 84% of participants in the ETT group and 85% participants in the IPT group. The median CD4 change at 24 weeks was 96 (IQR 55–147) in the ETT group and 102 (60–159) in the IPT group (p=0·25 by Wilcoxon test). Tuberculosis-immune reconstitution inflammatory syndrome cases were reported in 19 (2%) participants (9 in the ETT group and 10 in the IPT group). In conclusion, empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating ART. In patients with advanced HIV disease in settings where tuberculosis incidence is high, the low mortality rate of the trial supports urgent implementation of systematic tuberculosis screening and isoniazid preventive therapy before ART initiation.