American Journal of Epidemiology Copyright © 1995 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved Vol. 142, No. 12 Printed in U.S.A. Estimated Timing of Mother-to-Child Human Immunodeficiency Virus Type 1 (HIV-1) Transmission by Use of a Markov Model C. Rouzioux, 1 D. Costagliola, 2 M. Burgard, 1 S. Blanche, 3 M. J. Mayaux, 4 C. Griscelli, 3 A.-J. Valleron, 2 and the HIV Infection in Newborns French Collaborative Study Group 5 It has been shown that mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission can occur both during pregnancy and at delivery, but the respective frequencies in these periods are unknown. Moreover, it is difficult to determine the timing of mother-to-child HIV-1 transmission by direct sampling. The use of an elaborate statistical method is therefore necessary. The authors studied 495 consecutive infants born between May 1988 and August 1991 who were included, at birth, in the French Prospective Study on Pediatric HIV Infection. At least one blood sample was obtained from every infant during the first 14 days of life. All samples obtained within 3 months of birth were tested by at least two of the following methods: viral culture, polymerase chain reaction (PCR), and antigenemia, as well as by Western blot test. Data for the 95 infected infants (those seropositive at 18 months and those who died of HIV disease before this age), and who were exclusively bottle-fed, were analyzed in a Markov model to estimate the timing of viral transmission, the time from birth to the emergence of detectable virus, and the time from birth to seroconversion. The model indicated that one-third of the infants were infected in utero, less than 2 months before delivery (95th percentile). In the remaining 65% of cases (95% confidence interval (Cl) 22-92), the date of infection was estimated as the day of birth. The estimated median period between birth and the emergence of viral markers was 10 days (95% Cl 6-14) and the 95th percentile was estimated at 56 days. These results support the view that HIV infection can be diagnosed during the first 3 months of life. The authors conclude that mother-to-child HIV-1 transmission appears to occur late in pregnancy or at delivery. Am J Epidemiol 1995;142:1330-7. cohort studies; HIV-1; Markov models; mother-to-child transmission; statistics The mother-to-child human immunodeficiency vi- rus type 1 (HIV-1) transmission rate has been esti- Received for publication June 6, 1994, and in final form March 30, 1995. Abbreviations: AIDS, acquired immunodeficiency syndrome; anti-HIV-1, antibody to human immunodeficiency virus type 1; HIV-1, human immunodeficiency virus type 1; PBMC, peripheral blood mononuclear cells; PCR, polymerase chain reaction. 1 Laboratoire de Virologie, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75015 Paris, France. (Correspondence to Prof. C. Rouzioux at this address.) 2 B 3 E, INSERM U 263 et SC4, Universite Pierre et Marie Curie, Faculte de Medecine Saint-Antoine, Paris, France. 3 Unite d'lmmunologie-Hematologie, Hopital Necker-Enfants Malades, Paris, France. 4 INSERM U 292, Hopital du Kremlin-Bicetre, Le Kremlin-Bicetre, France. 5 The following persons are participants in the HIV Infection in Newborns French Collaborative Study: M. C. Allemon, D. Armengaud, J. M. Babinet, P. Balde, F. Ben Fadel, R. Bensadoun, D. Berterotiere, M. Boddaert, Y. Bompard, C. Botto, A. M. Brunner, J. A. Cacault, C. Carlus-Moncomble, N. Ciraru-Vigneron, C. Cohen, A. M. Colin-Gorki, C. Courpotin, C. Crumiere, M. C. Dallot, M. Dandine, A. De Crepy, M. Debons, M. Debre, M. F. Denavit, A. Devidas, M. Dumontel, G. Firtion, C. Floch, C. Francoual, J. Furioli, A. Gantzer, F. Granier, F. Guillot, B. Heller, C. Huraux-Rendu, P. Labrune, E. Lachassine, A. Lacroix, M. Lanza, H. Lajalle, B. Le Lorier, A. Leblanc, F. Lebrun, C. Lejeune, J. Mamou, A. May, F. Mazi, A. Meyer, G. Mouchnino, P. Narcy, G. Noseda, C. Pascal, B. mated at between 10 and 39 percent in epidemiologic studies (1). The timing of transmission is unknown, yet it is crucial to know for effective prevention. Lentiviruses, including HIV-1, replicate and can be detected in the blood throughout the course of the infection; HIV-1 is continuously present in the form of complete infectious virions in the plasma and as pro- viruses integrated in host lymphocyte DNA. This means that the fetus of an infected woman is, in theory, continuously exposed to the virus. Early trans- mission has been suggested by reports of HIV-1 DNA detection in aborted fetuses and fetal tissues taken during the first 6 months of pregnancy (2, 3), while other studies have pointed to later transmission in utero or during delivery (4, 5). HIV-1 is detectable at birth in only about 40 percent of infected infants (6,7), suggesting that infection occurs close to or during delivery in the remaining cases. Firstborn twins are more frequently infected than their siblings, which Pautard, M. Robin, M. Ronzier, J. L. Ropert, M. C. Rousset, A. Saillant, G. Scart, H. Seaume, D. Seguy, P. Talon, M. Tardieu, J. Terris, L. Valdes, F. Veber, J. Vedrenne, M. Vial, A. Vinas, N. Vincent, and P. Wipff. 1330