Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy

Background. Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. Methods. Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. Results. Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001 - 2003. The overall MTCT rate in this period was 2.87% ( 95% confidence interval [CI], 2.11% - 3.81%), but it was 0.99% ( 95% CI, 0.32% - 2.30%) during 2001 - 2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1;)and elective Caesarean section (AOR, 0.33;). Detection of maternal HIV RNA was significantly Pp. 003 Pp. 04 associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03 - 0.33), compared with vaginal delivery or emergency Caesarean section. Conclusions. Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important

Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women

Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life (P < .001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring

Increasing likelihood of further live births in HIV-infected women in recent years

Objective To examine how the subsequent childbearing of HIV-infected mothers enrolled in the European Collaborative Study (ECS) has changed over time and identify factors predictive of further childbearing. Design Prospective cohort study. Setting Centres in nine European countries included in the ECS, enrolled between end 1986 and November 2003. Population HIV-infected women (3911): 3693 with only one and 218 with subsequent live births. Methods Univariable and multivariable logistic regression analyses to obtain odds ratios (OR) and 95% confidence intervals (CI). Kaplan-Meier (KM) analyses to estimate cumulative proportions of women having a subsequent live birth. Main outcome measures Subsequent live birth. Results In multivariable analysis adjusting for time period, ethnicity, maternal age and parity, black women were more likely [adjusted odds ratio (AOR) 2.45; 95% CI, 1.75-3.43], and women > 30 years less likely (AOR 0.54, 0.37-0.80), to have a subsequent live birth. Time to subsequent live birth significantly shortened over time, with an estimated 2% of women having a subsequent live birth within 24 months of enrolment pre-1989 versus 14% in 2000-2003 (P < 0.001). Estimated time to subsequent live birth was shorter for black than for white women (P < 0.001). Conclusions The likelihood of subsequent live births substantially increased after 1995 and birth intervals were shorter in women on HAART and among black women. Numbers are currently too small to address the issue of advantages and disadvantages in the management of subsequent deliverie

Mode of delivery in HIV-infected pregnant women and prevention of mother-to-child transmission: changing practices in Western Europe

Objectives The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother-to-child transmission (MTCT). Methods The ECS is a cohort study in which HIV-infected pregnant women are enrolled and their infants prospectively followed. Data on 5238 mother\u2013child pairs (MCPs) enrolled in Western European ECS sites between 1985 and 2007 were analysed. Results The elective CS rate increased from 16% in 1985\u20131993 to 67% in 1999\u20132001, declining to 51% by 2005\u20132007. In 2002\u20132004, 10% of infants were delivered vaginally, increasing to 34% by 2005\u2013 2007. During the HAART era, women in Belgium, the United Kingdom and the Netherlands were less likely to deliver by elective CS than those in Italy and Spain [adjusted odds ratio (AOR) 0.07; 95% confidence interval (CI) 0.04\u20130.12]. The MTCT rate in 2005\u20132007 was 1%. Among MCPs with maternal HIV RNAo400 HIV-1 RNA copies/mL (n 5 960), elective CS was associated with 80% decreased MTCT risk (AOR 0.20; 95% CI 0.05\u20130.65) adjusting for HAART and prematurity. Two infants born to 559 women with viral loads o50 copies/mL were infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04\u20131.29). Conclusions Our findings suggest that elective CS prevents MTCT even at low maternal viral loads, but the study was insufficiently powered to enable a conclusion to be drawn as to whether this applies for viral loads o50 copies/mL. Diverging mode of delivery patterns in Europe reflect uncertainties regarding the risk\u2013benefit balance of elective CS for women on successful HAART