1. Extended pre-exposure prophylaxis with lopinavir–ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial
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Nicolas Nagot, Chipepo Kankasa, James K Tumwine, Nicolas Meda, G Justus Hofmeyr, Roselyne Vallo, Mwiya Mwiya, Mary Kwagala, Hugues Traore, Amwe Sunday, Mandisa Singata, Chafye Siuluta, Eric Some, David Rutagwera, Desire Neboua, Grace Ndeezi, Debra Jackson, Valérie Maréchal, Dorine Neveu, Ingunn M S Engebretsen, Carl Lombard, Stéphane Blanche, Halvor Sommerfelt, Claire Rekacewicz, Thorkild Tylleskär, Philippe Van de Perre, Valerie Marechal, Marianne Peries, Vincent Foulongne, Michel Segondy, Stephane Blanche, Jean-Marc Treluyer, Deborah Hirt, Charles Karamagi, Philippa Musoke, Proscovia M Mugaba, Joan Murungi, Hawa Nabuuma Muweesi, Evelyn Ninsiima, Simon Baryeija, Frederic Juma, Caleb Bwengye Kata, Stuart Katushabe, Rasmata Ouédraogo, Diarra Yé, Eric Somé, Hugues A Traoré, Christelle Nadembega, Justin Konaté, Arsène Zongo, Abass Ouédraogo, Désiré Néboua, Aissatou Bélemviré, Armel Bambara, Justine Boncoungou, Danielle Zoungrana, Cheryl Nikodem, Justus Hofmeyr, Kim Harper, David Sanders, Amwe Aku, Collins Okegbe-Eze, Xoliswa Williams, Nolundi Mshweshwe, Vatiswa Henge, Fikiswa Gomba, Tapiwa Gundu, Oswell Khondowe, Mildred Lusaka, Mary Chizyuka, Mary Phiri, Billies Imakando, Mwenechanya Musaku, Monica Kapasa, Gondwe Clement, Hilton Mwila Mwaba, Japhet Matoba, Katai Chola, Patricia Mwamutanda, Ingunn Engebretsen, Jørn Klungsøyr, Jan van den Broeck, Jörn Blume, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Pediatrics ,medicine.medical_specialty ,Anti-HIV Agents ,Population ,Breastfeeding ,Lopinavir/ritonavir ,HIV Infections ,030204 cardiovascular system & hematology ,Drug Administration Schedule ,Lopinavir ,law.invention ,03 medical and health sciences ,Pre-exposure prophylaxis ,0302 clinical medicine ,Randomized controlled trial ,Acquired immunodeficiency syndrome (AIDS) ,law ,medicine ,Humans ,030212 general & internal medicine ,education ,Africa South of the Sahara ,education.field_of_study ,Ritonavir ,business.industry ,Infant, Newborn ,Infant ,Obstetrics and Gynecology ,Lamivudine ,virus diseases ,General Medicine ,medicine.disease ,Infectious Disease Transmission, Vertical ,3. Good health ,Clinical trial ,Breast Feeding ,HIV-1 ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Drug Therapy, Combination ,Female ,Pre-Exposure Prophylaxis ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Breast feeding ,medicine.drug - Abstract
International audience; BACKGROUND: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding.METHODS: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263.FINDINGS: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group.INTERPRETATION: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding.FUNDING: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.
- Published
- 2016
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