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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

Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy

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

TEMPRANO

START

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

START
Published by François RAFFI

Updated: 11 September, 2015

INSIGHT START Study Group et al. N Engl J Med. 2015 Aug 27;373(9):795-807.

The Strategic Timing of Antiretroviral Therapy (START) study is a multicontinental randomised study designed to determine the risks and benefits of the immediate initiation of antiretroviral therapy in asymptomatic HIV positive patients who have CD4+ count > 500 cells/mm3 , as compared with deferring initiation until the CD4+ count is 350 cells/mm3 . Eligibility criteria were: HIV positivity, age ≥ 18 years, antiretroviral therapy naïve, no history of AIDS, general good health, two CD4+ counts >500 cells/mm3 at least 2 weeks apart within 60 days before enrollment. Patients were randomly assigned to 2 strategies for initiating antiretroviral therapy: immediate initiation and deferred initiation until the CD4+ count declined to 350 cells/mm3 or the development of an AIDS-related event or another condition that dictated the use of antiretroviral therapy (e.g., pregnancy). The primary composite end point was: serious AIDS-related event (death from AIDS, AIDS-defining event with the exception of nonfatal herpes simplex virus infection and esophageal candidiasis, and addition of Hodgkin's lymphoma) or serious non–AIDS-related event (cardiovascular disease, end-stage renal disease, decompensated liver disease, non–AIDS-defining cancer, and death from cause unrelated to AIDS). For the statistical analysis, the 2 study groups were compared according to the intention-to-treat principle. Time-to-event methods were used, including Kaplan–Meier survival curves and Cox proportional-hazards models, to compare the 2 groups for the primary end point, its 2 major components and death from any cause.

A total of 4,685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651/mm3 . On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval, 0.30 to 0.62; p < 0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; p < 0.001) and 0.61 (95% CI, 0.38 to 0.97; p = 0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count > 500 cells/mm3 . The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.

In conclusion, the initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count > 500 cells/mm3 provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells/mm3 .