Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

Abstract

BACKGROUND Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause. RESULTS A total of 4685 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 cells per cubic millimeter. 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 [CI], 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 of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)

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

“…To evaluate the impact of the guideline change on outcome 4, days from presentation to treatment initiation, we estimated Cox proportional hazards regression models, controlling for all covariates listed above as well as sex and age. Person‐time was censored at transfer to another clinic outside the Hlabisa system or 180 days of follow‐up.…”

“…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.…”

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.…”

Speaker Abstracts

“…The clinical presentation is non-specific and laboratory confirmation may be inaccurate [1]. Timely and optimal identification and treatment of patients during the acute phase of HIV infection impact the long-term outcome of the individual and transmission [2]. Even though universal access to antiretroviral treatment (ART) exists in Mexico [3], entering to care and initiating treatment in public institutions faces important bureaucratic, regulatory and administrative hurdles.…”