Antiretroviral therapy at conception in pregnant women with HIV in Italy: Wide range of variability and frequent exposure to contraindicated drugs

Methods: Data from a large national surveillance study was used to describe antiretroviral regimens in pregnant women with HIV, with particular reference to the presence at conception of antiretroviral treatments contraindicated in pregnancy. Therapeutic changes during pregnancy were also analysed. Results: Among 334 women on antiretroviral treatment at conception, less than half (42.4%) reported current pregnancy as planned. A large number of different regimens (80) was observed. All the regimens included at least one nucleoside or nucleotide reverse transcriptase inhibitor. Non-nucleoside reverse transcriptase inhibitors and protease inhibitors were present in similar proportions (39.2% and 40.7%, respectively). The most commonly used drugs were lamivudine (83.2% of regimens), zidovudine (50.0%), stavudine (d4T; 38.0%), nevirapine (25.7%), didanosine (ddl; 17.7%) and nelfinavir (17.7%). Treament with efavirenz (13.5% of regimens) and ddI+d4T (9.6%) was markedly frequent. Use of efavirenz at conception was associated with a subsequent treatment change during pregnancy (odds ratio [OR]: 13.2.; 95% confidence interval [CI]: 3.2-53.8, P < 0.001). A similar but less strong association was found for ddI (OR: 1.8; 95% CI: 1.03-3.25, P=0.033), whereas being on nevirapine was associated with a lower risk (OR: 0.58; 95% CI: 0.38-0.81, P=0.013). Conclusions: Our data show that treatment at conception frequently represents the regimen previously selected for the treatment of the non-pregnant woman. The observed rates of exposure to contraindicated treatment should lead prescribing physicians to consider in HIV-positive women therapeutic choices that take into account the likelihood of an unplanned pregnancy. Such an approach is likely to reduce not only unintended exposures to contraindicated drugs, but also therapeutic changes during pregnancy

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

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

Combination antiretroviral therapy and duration of pregnancy

OBJECTIVE: To assess the association between type and timing of initiation of antiretroviral therapy in pregnancy and duration of pregnancy. DESIGN: Prospective study. METHODS: Data on 3920 mother-child pairs were examined (3015 mother-child pairs from the European Collaborative Study and 905 from the Swiss Mother + Child HIV Cohort Study). Factors examined included gestational age, antiretroviral therapy during pregnancy, maternal CD4 count, viral load, illicit drug use (IDU) and mode of delivery. Deliveries at less than 37 weeks were defined as premature. RESULTS: The prematurity rate was 17% and median gestational age 39 weeks. Twenty-three per cent (896 of 3920) of women received antiretroviral therapy during pregnancy: 64% (573 of 896) zidovudine monotherapy, 24% (215) combination therapy without protease inhibitors (PI) and 12% (108) combination therapy with PI. In multivariate analysis, adjusted for maternal CD4 count and IDU, odds ratio (OR) of prematurity was 2.60 [95% confidence interval (CI), 1.43-4.75] and 1.82 (95% CI, 1.13-2.92) for infants exposed to combination therapy with and without a PI, respectively, compared to no treatment. Exposure to monotherapy was not associated with prematurity, but severe immunosuppression and IDU in pregnancy were. Women on combination therapy from before pregnancy were twice as likely to deliver prematurely as those starting therapy in the third trimester (OR, 2.17; 95% CI, 1.03-4.58). CONCLUSIONS: Pregnancy issues should be discussed when making decisions about initiation of combination antiretroviral therapy for HIV-infected women. Elective caesarean section to reduce vertical transmission at 36 weeks rather than 38 weeks may be advisable in women on combination therapy with PI

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

Objective: 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 >= 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% Cl -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% Cl -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% Cl 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. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved

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

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