Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes

Anderson, Maija

Celentano, David

Chariyalertsak, Suwat

Chen, Ying Q

Cohen, Myron S

Eron, Joseph

Eshleman, Susan H

Essex, Max

Gallant, Joel

Gamble, Teresa

Godbole, Sheela V

Grinsztein, Beatriz

Hakin, James G

Havlir, Diane

Hoffman, Irving

Hosseinipour, Mina C

Kumarasamy, Nagalingeshwaran

Kumwenda, Johnstone

Makhema, Joseph

Mayer, Kenneth H

McCauley, Marybeth

Melo, Marineide Gonçalves de

Mills, Lisa A

Nielsen-Seines, Karin

Ou, San-San

Panchia, Ravindre

Pilotto, José Henrique

Piwowar-Manning, Estelle

Ribaudo, Heather J

Sanne, Ian

Swindells, Susan

Taha, T E

Wang, Lei

PubMed

Grinsztejn, Beatriz

Gamble, Theresa

Hakim, James G

Pilotto, Jose H S

de Melo, Marineide Gonçalves

Taha, Taha E

Nielsen-Saines, Karin

Carolina Digital Repository

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

Funding US National Institute of Allergy and Infectious DiseasesBackground Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality
and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce
progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral
treatment reduced HIV-1 transmission by 96%. We aimed to compare the eff ects of early and delayed initiation of
antiretroviral treatment on clinical outcomes.
Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled
HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral
treatment by use of permuted block randomisation, stratifi ed by site. Random assignment was unblinded. The
HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early
treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment
group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial
infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular
disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant
disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581.
Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned
early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group
after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to
the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the
delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197–249) cells per μL. Primary
clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed
antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52–1·03; p=0·074). New-onset AIDS events were recorded in
40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43–0·96;
p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28–0·89, p=0·018), and primary non-
AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary
outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5–27·5) versus 585 in
the delayed treatment group (29·2 per 100 person-years, 26·5–32·1; p=0·025). 26 people died, 11 who were allocated to
early antiretroviral treatment and 15 who were assigned to the delayed treatment group.
Interpretation Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of
primary and secondary outcomes. The clinical benefi ts recorded, combined with the striking reduction in HIV-1
transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment

RCAAP - Repositório Científico de Acesso Aberto de Portugal

http://dx.doi.org/10.1016/S1473-3099(13)70692-3

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

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