title: Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV.
abstract: BACKGROUND
  Antiretroviral treatments decrease HIV mother-to-child transmission through pre/post exposure prophylaxis and reduction of maternal viral load. We modeled in-utero and intra-partum HIV transmissions to investigate the preventive role of various antiretroviral treatments interventions.
  
  
  METHODS
  We analysed data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of mother-to-child transmission of HIV in Thailand. All infants were formula-fed. Non-linear mixed effect modeling was used to express the viral load evolution under antiretroviral treatments and the probability of transmission.
  
  
  RESULTS
  Median viral load was 4 log10 copies/mL (Interquartile range: 3.36-4.56) before antiretroviral treatments initiation. An Emax model described the viral load time-course during pregnancy. Half of the maximum effect of zidovudine (28% decrease) and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days, respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95% confidence interval: 1.34, 1.68] per log10 copies/mL increment), antiretroviral treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the nature of antiretroviral treatments were associated with in-utero transmission. Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]), baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm3 increment) and predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log10 copies/mL increment), single-dose nevirapine considerably reduced intra-partum transmission (OR = 0.32 [0.2, 0.51]).
  
  
  CONCLUSIONS
  These models determined the respective contributions of various antiretroviral strategies on prevention of mother-to-child transmission. This can help predict the efficacy of new antiretroviral treatments and/or prevention of mother-to-child transmission strategies particularly for women with no or late antenatal care who are at high risk of transmitting HIV to their offspring.
  
  
  BACKGROUND
  This analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. NCT00386230, NCT00398684, NCT00409591.
authors.affiliation: Department of Statistics, Kasetsart University, Bangkok, Thailand; Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; Ecole Doctorale de Santé Publique, Université Paris-Sud, Paris, France.
authors.forename: Patumrat
authors.initials: P
authors.lastname: Sripan
authors.affiliation: Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand; Institut d'Etudes Démographiques, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Coeur
authors.affiliation: Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; LASER Analytica, London, United Kingdom.
authors.forename: Billy
authors.initials: B
authors.lastname: Amzal
authors.affiliation: Department of Statistics, Kasetsart University, Bangkok, Thailand.
authors.forename: Lily
authors.initials: L
authors.lastname: Ingsrisawang
authors.affiliation: Department of Statistics, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Patrinee
authors.initials: P
authors.lastname: Traisathit
authors.affiliation: Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ngo-Giang-Huong
authors.affiliation: Boston Children's Hospital, Boston, MA, United States of America; Department of Pediatrics, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: McIntosh
authors.affiliation: Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.affiliation: Health Promotion Center Region 10, Chiang Mai, Thailand.
authors.forename: Suraphan
authors.initials: S
authors.lastname: Sangsawang
authors.affiliation: Nopparat Rajathanee Hospital, Bangkok, Thailand.
authors.forename: Boonsong
authors.initials: B
authors.lastname: Rawangban
authors.affiliation: Banglamung Hospital, Chonburi, Thailand.
authors.forename: Prateep
authors.initials: P
authors.lastname: Kanjanavikai
authors.affiliation: EAU08 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France; CIC1419 INSERM, Cochin-Necker, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
authors.affiliation: Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; Department of Medical Technology, Faculty of Associated Medical Science, Chiang Mai University, Chiang Mai, Thailand;  Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Gonzague
authors.initials: G
authors.lastname: Jourdain
authors.affiliation: Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France; Department of Medical Technology, Faculty of Associated Medical Science, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Marc
authors.initials: M
authors.lastname: Lallemant
authors.affiliation: EAU08 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France; CIC1419 INSERM, Cochin-Necker, Paris, France.
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
mesh_terms: D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008962:Models, Theoretical; D011247:Pregnancy; D019562:Viral Load