Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 ≥ 400 cells/mm3.

TitleRandomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 ≥ 400 cells/mm3.
Publication TypeJournal Article
Year of Publication2017
AuthorsCurrier JS, Britto P, Hoffman RM, Brummel S, Masheto G, Joao E, Santos B, Aurpibul L, Losso M, Pierre MF, Weinberg A, Gnanashanmugam D, Chakhtoura N, Klingman K, Browning R, Coletti A, Mofenson L, Shapiro D, Pilotto J
Corporate Authors1077HS PROMISE Team
JournalPLoS One
Volume12
Issue5
Paginatione0176009
Date Published2017
ISSN1932-6203
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections, Humans, Postpartum Period, Viral Load
Abstract

BACKGROUND: Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials.

METHODS: Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat.

RESULTS: 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696 cells/mm3 (IQR 575-869), median ART exposure prior to delivery was 19 weeks (IQR 13-24) and 94% had entry HIV-1 RNA < 1000 copies/ml. After a median follow-up of 2.3 years, the primary composite endpoint rate was significantly lower than expected, and not significantly different between arms (continue arm 0.21 /100 person years(py); discontinue 0.31/100 py, Hazard ratio (HR) 0.68, 95% CI: 0.19, 2.40). WHO Stage 2 and 3 events were significantly reduced with continued ART (2.08/100 py vs. 4.36/100 py in the discontinue arm; HR 0.48, 95%CI: 0.33, 0.70). Toxicity rates did not differ significantly between arms. Among women randomized to continue ART, 189/827 (23%) had virologic failure; of the 155 with resistance testing, 103 (66%) failed without resistance to their current regimen, suggesting non-adherence.

CONCLUSIONS: Overall, serious clinical events were rare among young HIV-positive post-partum women with high CD4 cell counts. Continued ART was safe and was associated with a halving of the rate of WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent need to improve adherence in this population.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00955968.

DOI10.1371/journal.pone.0176009
Alternate JournalPLoS ONE
PubMed ID28489856
PubMed Central IDPMC5425014
Grant ListUM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069456 / AI / NIAID NIH HHS / United States
UM1 AI068632 / AI / NIAID NIH HHS / United States
UM1 AI069399 / AI / NIAID NIH HHS / United States
UM1 AI068616 / AI / NIAID NIH HHS / United States
UM1 AI106716 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States