Statistical considerations for the HPTN 052 Study to evaluate the effectiveness of early versus delayed antiretroviral strategies to prevent the sexual transmission of HIV-1 in serodiscordant couples.
The HIV Prevention Trial Network (HPTN) 052 Study is a Phase III, two-arm, controlled, open-labeled, randomized clinical trial designed to determine whether early antiretroviral therapy (ART) can prevent the sexual transmission of human immunodeficiency virus type 1 (HIV-1). A total of 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative were enrolled in four continents, nine countries and thirteen study sites. The HIV-1-positive partner was randomly assigned to either of the two arms: "immediate" (early) therapy with ART initiated upon enrollment plus HIV primary care, or "delayed" therapy with HIV primary care but ART initiated when the index case would have two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm(3), or develop an AIDS-defining illness. In this paper, we describe several key statistical considerations for the design of this landmark study. Despite that the observed event rates were lower than expected, which might have compromised the study power, an early release of the trial results in May 2011 showed an overwhelming 96% risk reduction for the immediate therapy in the prevention of genetically linked HIV-1 incident transmissions. Nevertheless, the durability of its long-term effectiveness is yet to be assessed. The HPTN 052 Study is still ongoing and will not complete till 2015.
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. yqchen@fhcrc.org
Ying Qing
YQ
Chen
Benoit
B
Masse
Lei
L
Wang
San-San
SS
Ou
Xin
X
Li
Deborah
D
Donnell
Marybeth
M
McCauley
Theresa
T
Gamble
Heather J
HJ
Ribauldo
Myron S
MS
Cohen
Thomas R
TR
Fleming
D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D012747:Sexual Partners; D013997:Time Factors
D044966:Anti-Retroviral Agents