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

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

The mother-to-child HIV transmission epidemic in Europe: evolving in the East and established in the West

OBJECTIVES: To carry out an epidemiological analysis of the emerging epidemic in an Eastern European country and to compare the approach to prevention of mother-to-child transmission (MTCT) with that in Western Europe. DESIGN: Prospective cohort study established in 1985 in Western Europe and extended to Ukraine in 2000. METHODS: Data on 5967 HIV-infected pregnant women and their infants (1251 from Ukraine and 4716 from Western/Central Europe) was analysed. Factors associated with transmission were identified with logistic regression. RESULTS: HIV-infection among pregnant women enrolled in Western European centres has shifted from being largely injecting drug use (IDU)-related to heterosexually-acquired; in Ukraine IDU also gradually declined with women increasingly identified without specific risk factors. In Ukraine in 2000-2004 most (80%) women received single dose nevirapine (sdNVP) and/or short-course zidovudine prophylaxis [MTCT rate 4.2%; 95% confidence interval (CI), 1.8-8.0 for sdNVP with short-course zidovudine]; 2% (n = 27) received antenatal HAART and 33% (n = 418) delivered by elective caesarean section (CS); in Western European centres 72% of women received HAART (MTCT rate 1.0%; 95% CI, 0.4-1.9) and 66% delivered by elective CS during the same period. CONCLUSIONS: Our findings indicate distinct differences in the epidemics in pregnant women across Europe. The evolution of the MTCT epidemic in Ukraine does not appear to be following the same pattern as that in Western Europe in the 1980s and 1990s. Although uptake of preventive MTCT prophylaxis has been rapid in both Western Europe and Ukraine, substantial challenges remain in the more resource-constrained setting in Eastern Europe

Levels and patterns of HIV RNA viral load in untreated pregnant women.

none101OBJECTIVE: To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race. METHODS: Data on > or = 1 antenatal HIV RNA measurements were available for 333 untreated HIV-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested random effects term accounting for measurement variability within women and period of sample collection. RESULTS: The change in HIV RNA over pregnancy varied significantly by race (p=0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies/ml/week in white women (95% CI -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% CI -0.005, 0.037) was not statistically significant. At delivery, HIV RNA levels in black women were 0.45 log(10) copies/ml higher (95% CI 0.08, 0.83) than in white women. CONCLUSIONS: Our findings suggest that HIV RNA dynamics over pregnancy differ by race, although other interpretations cannot be excluded, due to potential for unmeasured confounding.mixedGIAQUINTO C; RAMPON O; D'ELIA R; DE ROSSI A; GROSCH-WÖRNER I; MOK J; DE JOSÉ MI; LARRÚ MARTÍNEZ B; PEÑA JM; GONZALEZ GARCIA J; ARRIBAS LOPEZ JR; GARCIA-RODRIGUEZ MC; ASENSI-BOTET F; OTERO MC; PÉREZ-TAMARIT D; SCHERPBIER HJ; KREYENBROEK M; GODFRIED MH; NELLEN FJ; BOER K; EHRNST A; BOHLIN AB; LINDGREN S; ANZÉN B; LIDMAN K; LEVY J; BARLOW P; MANIGART Y; HAINAUT M; GOETGHEBUER T; FERRAZIN A; VISCOLI C; DEMARIA A; BENTIVOGLIO G; S. FERRERO; GOTTA C; MÛR A; PAYÀ A; LÓPEZ-VILCHEZ MA; CARRERAS R; VALERIUS NH; ROSENFELDT V; JIMENEZ J; COLL O; SUY A; PEREZ JM; FORTUNY C; BOGUÑA J; CASELLAS CARO M; CANET Y; RAVIZZA M; GUERRA B; LANARI M; BIANCHI S; BOVICELLI L; PRATI E; DUSE M; SCARAVELLI G; STEGAGNO M; DE SANTIS M; SAVASI V; FIORE S; CRIVELLI M; FERRAZZI E; VIGANÒ A; GIACOMET V; CERINI C; RAIMONDI C; ZUCCOTTI G; RAVAGNI PROBIZER F; MACCABRUNI A; BUCCERI A; RANCILIO L; ALBERICO S; RABUSIN M; BERNARDON M; TAYLOR GP; LYALL EG; PENN Z; BUFFOLANO W; TISEO R; MARTINELLI P; SANSONE M; MARUOTTI G; AGANGI A; TIBALDI C; MARINI S; MASUELLI G; BENEDETTO C; NIEMIEÇ T; MARCZYNSKA M; DOBOSZ S; POPIELSKA J; OLDAKOWSKA A; MALYUTA R; SEMENENKO I; PILIPENKO T; POSOKHOVA S; KALEEVA T; STELMAH A; KISELEVA GGiaquinto, C; Rampon, O; D'Elia, R; DE ROSSI, A; GROSCH WÖRNER, I; Mok, J; DE JOSÉ, Mi; LARRÚ MARTÍNEZ, B; Peña, Jm; GONZALEZ GARCIA, J; ARRIBAS LOPEZ, Jr; GARCIA RODRIGUEZ, Mc; ASENSI BOTET, F; Otero, Mc; PÉREZ TAMARIT, D; Scherpbier, Hj; Kreyenbroek, M; Godfried, Mh; Nellen, Fj; Boer, K; Ehrnst, A; Bohlin, Ab; Lindgren, S; Anzén, B; Lidman, K; Levy, J; Barlow, P; Manigart, Y; Hainaut, M; Goetghebuer, T; Ferrazin, A; Viscoli, Claudio; DE MARIA, Andrea; Bentivoglio, Giorgio; Ferrero, Simone; Gotta, C; Mûr, A; Payà, A; LÓPEZ VILCHEZ, Ma; Carreras, R; Valerius, Nh; Rosenfeldt, V; Jimenez, J; Coll, O; Suy, A; Perez, Jm; Fortuny, C; Boguña, J; CASELLAS CARO, M; Canet, Y; Ravizza, M; Guerra, B; Lanari, M; Bianchi, S; Bovicelli, L; Prati, E; Duse, M; Scaravelli, G; Stegagno, M; DE SANTIS, M; Savasi, V; Fiore, S; Crivelli, M; Ferrazzi, E; Viganò, A; Giacomet, V; Cerini, C; Raimondi, C; Zuccotti, G; RAVAGNI PROBIZER, F; Maccabruni, A; Bucceri, A; Rancilio, L; Alberico, S; Rabusin, M; Bernardon, M; Taylor, Gp; Lyall, Eg; Penn, Z; Buffolano, W; Tiseo, R; Martinelli, P; Sansone, M; Maruotti, G; Agangi, A; Tibaldi, C; Marini, S; Masuelli, G; Benedetto, C; Niemieç, T; Marczynska, M; Dobosz, S; Popielska, J; Oldakowska, A; Malyuta, R; Semenenko, I; Pilipenko, T; Posokhova, S; Kaleeva, T; Stelmah, A; Kiseleva, G