Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.
Adult
Alkynes
Anti-HIV Agents
/ adverse effects
Benzoxazines
/ adverse effects
Cyclopropanes
Drug Therapy, Combination
Female
HIV Infections
/ drug therapy
HIV Integrase Inhibitors
/ therapeutic use
Humans
Infant, Newborn
Infectious Disease Transmission, Vertical
/ prevention & control
Lamivudine
/ therapeutic use
Outcome Assessment, Health Care
Pregnancy
Pregnancy Complications, Infectious
/ drug therapy
Raltegravir Potassium
/ adverse effects
Viral Load
/ drug effects
Young Adult
Zidovudine
/ therapeutic use
Journal
The lancet. HIV
ISSN: 2352-3018
Titre abrégé: Lancet HIV
Pays: Netherlands
ID NLM: 101645355
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
27
11
2019
revised:
26
01
2020
accepted:
31
01
2020
entrez:
11
5
2020
pubmed:
11
5
2020
medline:
1
9
2020
Statut:
ppublish
Résumé
Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.
Sections du résumé
BACKGROUND
Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy.
METHODS
An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305.
FINDINGS
From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths.
INTERPRETATION
Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV.
FUNDING
Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.
Identifiants
pubmed: 32386720
pii: S2352-3018(20)30038-2
doi: 10.1016/S2352-3018(20)30038-2
pmc: PMC7323582
mid: NIHMS1593997
pii:
doi:
Substances chimiques
Alkynes
0
Anti-HIV Agents
0
Benzoxazines
0
Cyclopropanes
0
HIV Integrase Inhibitors
0
Lamivudine
2T8Q726O95
Raltegravir Potassium
43Y000U234
Zidovudine
4B9XT59T7S
efavirenz
JE6H2O27P8
Banques de données
ClinicalTrials.gov
['NCT01618305']
Types de publication
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e322-e331Subventions
Organisme : NICHD NIH HHS
ID : HHSN275201800001C
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068632
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH083308
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069453
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068616
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027757
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106716
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201800001I
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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