Treatment as prevention: a replication study on early antiretroviral therapy initiation and HIV-1 acquisition

Replication paper
Original publication: New England Journal of Medicine
Original researchers: Myron S Cohen, Ying Q Chen, Marybeth McCauley, Theresa Gamble, Mina C Hosseinipour, Nagalingeswaran Kumarasamy, James G Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose HS Pilotto, Sheela V Godbole, Sanjay Mehendale, Suwat Chariyalertsak, Breno R. Santos, Kenneth H. Mayer, Irving F. Hoffman, Susan H. Eshleman, Estelle Piwowar-Manning, Lei Wang, Joseph Makhema, Lisa A. Mills, Guy de Bruyn, Ian Sanne, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Heather Ribaudo, Vanessa Elharrar, David Burns, Taha E. Taha, Karin Nielsen-Saines, David Celentano, Max Essex, Thomas R. Fleming
Replication researchers: Eric Djimeu, Eleanor G Dickens
Current status: Completed Replication Study

The Original Study

Several observational studies have reported that the early use of antiretroviral therapy by patients diagnosed with HIV decreases rates of HIV acquisition among their sexual partners. This study evaluates the impact of early antiretroviral therapy on HIV acquisition among serodiscordant couples from nine countries. Specifically, half of 1,723 serodiscordant couples in which HIV-1-infected participants had a CD4 count of 350 to 550 cells per cubic millimeter were randomly assigned to receive antiretroviral therapy immediately (early therapy) while the other half received antiretroviral therapy after a decline in their CD4 count (250 cells per cubic millimeter) or after the onset of HIV-1-related symptoms (delayed therapy). The primary outcome of interest was the link between HIV-1 transmission and HIV-1 negative partners. In order to determine the impact of early therapy, the authors used the Kaplan–Meier method to calculate event-free probabilities and person-year analysis for incidence rate for a given year. They also used Cox regression to estimate relative risks and adjusted for potential prognostic factors. Finally, they used chi-square tests to compare the frequencies of adverse events. The study concluded that early initiation of antiretroviral therapy reduces rates of sexual transmission of HIV-1 and clinical events in HIV negative partners.

The Replication

Early antiretroviral therapy (ART) of an HIV-1-infected individual has been shown to lower the risk of transmitting HIV to his or her uninfected partner, as first shown in the study known as HPTN052 published by Cohen and colleagues (2011). It had been a common practice to delay ART until an individual’s CD4 count fell below a specific level; however, based on the HPTN052 study and other studies, the World Health Organization recommended that anyone infected with HIV-1 should begin ART as soon as possible, after diagnosis. This paper presents a replication study of the HPTN052 study by Cohen and colleagues using the data shared by the original authors. Applying the methods described in the original paper, this paper conducts a pure replication and follows with additional robustness checks to test the strength of the conclusions of the original paper.