Tags

Type your tag names separated by a space and hit enter

Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.
Lancet HIV. 2020 May; 7(5):e322-e331.LH

Abstract

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.

Authors+Show Affiliations

Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. Electronic address: esaujoao@gmail.com.Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Maternal and Pediatric Infectious Diseases Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil; Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil; Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil.Kilimanjaro Christian Medical University College, Moshi, Tanzania.Kilimanjaro Christian Medical University College, Moshi, Tanzania.Kilimanjaro Christian Medical University College, Moshi, Tanzania.Perinatal HIV Research Unit, University of the Witwatersrand, Johanesburg, South Africa.Perinatal HIV Research Unit, University of the Witwatersrand, Johanesburg, South Africa.Perinatal HIV Research Unit, University of the Witwatersrand, Johanesburg, South Africa.Hospital Geral de Nova Iguaçu, Nova Iguaçu, Brazil.Hospital Geral de Nova Iguaçu, Nova Iguaçu, Brazil.Fundacion Huesped, Buenos Aires, Argentina.Fundacion Huesped, Buenos Aires, Argentina.Bhumibol Adulyadej Hospital, Bangkok, Thailand.PHPT/IRD 174, Faculty of Associated Medical Sciences, Chiang Mai University and Chiangrai Prachanukroh Hospital, Chiang Mai, Thailand.Bhumibol Adulyadej Hospital, Bangkok, Thailand.Bhumibol Adulyadej Hospital, Bangkok, Thailand.Westat, Rockville, MD, USA.Westat, Rockville, MD, USA.University of Washington and Seattle Children's Hospital, Seattle, WA, USA.University of Southern California, Los Angeles, CA, USA.University of California San Diego, San Diego, CA, USA.US Agency for International Development, Washington, DC, USA.Boston University School of Medicine, Boston, MA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32386720

Citation

João, Esaú C., et al. "Raltegravir Versus Efavirenz in Antiretroviral-naive Pregnant Women Living With HIV (NICHD P1081): an Open-label, Randomised, Controlled, Phase 4 Trial." The Lancet. HIV, vol. 7, no. 5, 2020, pp. e322-e331.
João EC, Morrison RL, Shapiro DE, et al. Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial. Lancet HIV. 2020;7(5):e322-e331.
João, E. C., Morrison, R. L., Shapiro, D. E., Chakhtoura, N., Gouvèa, M. I. S., de Lourdes B Teixeira, M., Fuller, T. L., Mmbaga, B. T., Ngocho, J. S., Njau, B. N., Violari, A., Mathiba, R., Essack, Z., Pilotto, J. H. S., Moreira, L. F., Rolon, M. J., Cahn, P., Prommas, S., Cressey, T. R., ... Mirochnick, M. (2020). Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial. The Lancet. HIV, 7(5), e322-e331. https://doi.org/10.1016/S2352-3018(20)30038-2
João EC, et al. Raltegravir Versus Efavirenz in Antiretroviral-naive Pregnant Women Living With HIV (NICHD P1081): an Open-label, Randomised, Controlled, Phase 4 Trial. Lancet HIV. 2020;7(5):e322-e331. PubMed PMID: 32386720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial. AU - João,Esaú C, AU - Morrison,R Leavitt, AU - Shapiro,David E, AU - Chakhtoura,Nahida, AU - Gouvèa,Maria Isabel S, AU - de Lourdes B Teixeira,Maria, AU - Fuller,Trevon L, AU - Mmbaga,Blandina T, AU - Ngocho,James S, AU - Njau,Boniface N, AU - Violari,Avy, AU - Mathiba,Ruth, AU - Essack,Zaakirah, AU - Pilotto,Jose Henrique S, AU - Moreira,Luis Felipe, AU - Rolon,Maria Jose, AU - Cahn,Pedro, AU - Prommas,Sinart, AU - Cressey,Timothy R, AU - Chokephaibulkit,Kulkanya, AU - Werarak,Peerawong, AU - Laimon,Lauren, AU - Hennessy,Roslyn, AU - Frenkel,Lisa M, AU - Anthony,Patricia, AU - Best,Brookie M, AU - Siberry,George K, AU - Mirochnick,Mark, PY - 2019/11/27/received PY - 2020/01/26/revised PY - 2020/01/31/accepted PY - 2021/05/01/pmc-release PY - 2020/5/11/entrez PY - 2020/5/11/pubmed PY - 2020/5/11/medline SP - e322 EP - e331 JF - The lancet. HIV JO - Lancet HIV VL - 7 IS - 5 N2 - 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. SN - 2352-3018 UR - https://www.unboundmedicine.com/medline/citation/32386720/Raltegravir_versus_efavirenz_in_antiretroviral-naive_pregnant_women_living_with_HIV_(NICHD_P1081):_an_open-label,_randomised,_controlled,_phase_4_trial L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3018(20)30038-2 DB - PRIME DP - Unbound Medicine ER -