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

Autor: 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
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Zdroj: PLoS ONE; May2015, Vol. 10 Issue 5, p1-16, 16p
Abstrakt: 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]). Conclusion: 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. Trial Registration: This analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. , , . [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index