Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV

• Published in: PloS one Vol. 10; no. 5; p. e0126647
• Main Authors: Sripan, Patumrat, Le Coeur, Sophie, Amzal, Billy, Ingsrisawang, Lily, Traisathit, Patrinee, Ngo-Giang-Huong, Nicole, McIntosh, Kenneth, Cressey, Tim R, Sangsawang, Suraphan, Rawangban, Boonsong, Kanjanavikai, Prateep, Tréluyer, Jean-Marc, Jourdain, Gonzague, Lallemant, Marc, Urien, Saïk
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.05.2015; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Analysis; Antiretroviral agents; Antiretroviral drugs; CD4 antigen; Clinical trials; Collaboration; Confidence intervals; Data processing; Disease transmission; Dosage; Female; Gestational age; Gynecology and obstetrics; Health risks; Highly active antiretroviral therapy; HIV; HIV Infections - prevention & control; HIV Infections - transmission; Human health and pathology; Human immunodeficiency virus; Humans; Infant; Infants; Infectious Disease Transmission, Vertical; Infectious diseases; Life Sciences; Lopinavir; Mathematical models; Medical research; Modelling; Models, Theoretical; Nevirapine; Offspring; Pregnancy; Prevention; Prophylaxis; Ritonavir; Santé publique et épidémiologie; Statistical analysis; Viral Load; Womens health; Zidovudine; Vertical; Pregnancy; HIV Infections/prevention & control/transmission; Humans; Female; Infant; Models; Infectious Disease Transmission; Viral Load; Theoretical
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126647

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. 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. 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]). 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. This analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. NCT00386230, NCT00398684, NCT00409591.