Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

Autor: Constance, Delaugerre, Marie-Laure, Chaix, Stephane, Blanche, Josiane, Warszawski, Dorine, Cornet, Catherine, Dollfus, Veronique, Schneider, Marianne, Burgard, Albert, Faye, Laurent, Mandelbrot, Roland, Tubiana, Christine, Rouzioux, S, Tilouche
Přispěvatelé: BMC, Ed., Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Virologie [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), Service d'immuno-hématologie pédiatrique [CHU Necker], Santé reproductive, sexualité, infection à VIH - épidémiologie, démographie, sciences sociales, Institut national d'études démographiques (INED)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de gynécologie obstétrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Louis Mourier - AP-HP [Colombes], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANRS French Perinatal Cohort, Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut national d'études démographiques ( INED ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pédiatrie et oncologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service de virologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hopital Louis Mourier - AP-HP [Colombes], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Pediatrics
MESH: Chemoprevention
HIV Infections
MESH : Genotype
Drug resistance
MESH: Genotype
MESH: HIV-1
0302 clinical medicine
MESH: Pregnancy
Pregnancy
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH : Chemoprevention
MESH : Female
030212 general & internal medicine
MESH : DNA
Viral
Pregnancy Complications
Infectious
MESH : Infectious Disease Transmission
Vertical
MESH: Treatment Outcome
0303 health sciences
education.field_of_study
Maternal Transmission
MESH : Prognosis
MESH: Drug Resistance
Viral
MESH: Infant
Newborn
MESH : Infant
MESH: HIV Infections
Prognosis
MESH: Infant
3. Good health
MESH : Antiviral Agents
MESH: Infectious Disease Transmission
Vertical
MESH : Drug Resistance
Viral
[ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Infectious Diseases
Treatment Outcome
MESH: RNA
Viral
Cohort
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
RNA
Viral
Female
MESH : HIV-1
lcsh:Immunologic diseases. Allergy
MESH: Antiviral Agents
medicine.medical_specialty
Genotype
Population
MESH : Treatment Outcome
Biology
MESH : Infant
Newborn
Antiviral Agents
Chemoprevention
MESH: Prognosis
03 medical and health sciences
Pharmacotherapy
Virology
Drug Resistance
Viral
medicine
MESH : HIV Infections
Humans
MESH : RNA
Viral
MESH: Pregnancy Complications
Infectious
education
Genotyping
MESH: Humans
030306 microbiology
Research
MESH : Humans
Infant
Newborn
Infant
medicine.disease
Reverse transcriptase
Infectious Disease Transmission
Vertical
MESH: DNA
Viral
MESH : Pregnancy
MESH : Pregnancy Complications
Infectious
Immunology
DNA
Viral
HIV-1
lcsh:RC581-607
MESH: Female
Zdroj: Retrovirology
Retrovirology, BioMed Central, 2009, 6 (1), pp.85. ⟨10.1186/1742-4690-6-85⟩
Retrovirology, BioMed Central, 2009, 6 (1), pp.85. 〈10.1186/1742-4690-6-85〉
Retrovirology, Vol 6, Iss 1, p 85 (2009)
ISSN: 1742-4690
DOI: 10.1186/1742-4690-6-85⟩
Popis: Background Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns. Patients and Methods We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing. Results Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%): drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10) and neonatal lymphocytes (2/8) suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped. Conclusion This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%), drug resistance was archived in the cellular reservoir and persisted during infancy, with or without antiretroviral treatment. This finding stresses the need for effective antiretroviral treatment of pregnant women.
Databáze: OpenAIRE
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