Link between the X4 phenotype in human immunodeficiency virus type 1-infected mothers and their children, despite the early presence of R5 in the child

Coreceptor use was determined for human immunodeficiency virus type 1 (HIV-1) isolates of various subtypes from 11 women during pregnancy and their infected children. Isolates from peripheral blood mononuclear cells (n = 79) and from plasma (n = 59) were available. The clinical and immunological stages of HIV-1 infection were recorded. Coreceptor use was tested on human cell lines expressing CD4 and different chemokine receptors. The R5 virus predominated, and only 9 isolates from 2 mothers used CXC chemokine receptor 4. All children carried the R5 virus at the time of diagnosis of HIV-1 infection. In 2 children of mothers carrying the X4 virus, the virus switched from R5 to X4 or to R5X4 by age 18 months (child no. 9) and age 48 months (child no. 10), whereas no children followed up to a similar age whose mothers were carrying the R5 virus experienced such a switch (). This points to a link between the P = .048 presence of X4 virus in the mother and the emergence of X4 virus in her child

Prevalence and risk factors of HSV-1 and HSV-2 antibodies in european HIV infected women

Objectives: To investigate the prevalence and risk factors of HSV-1 and HSV-2 antibodies in HIV infected women and the association between recurrent genital ulcerations and HIV disease progression in HSV-2 positive women. Methods: The presence of HSV antibodies was tested in 276 of the 487 women participating in a European cohort study of HIV infected women. Prevalence rate ratios described the association between HSV infection and its risk factors, using log binomial regression. Generalised estimating equations (GEE) analysis was performed to determine the impact of markers of HIV disease progression on recurrent genital ulcerations. Results: The prevalence of HSV-1 and HSV-2 antibodies was 76% (95% confidence interval (95% CI): 71-81) and 42% (95% CI: 36-50); 30% (95% CI: 24-35) of the women had antibodies against both HSV-1 and HSV-2. The prevalence of HSV-1 was 86% (95% CI: 80-92) in southern Europe compared with 69% (95% CI: 57-79) and 67% (95% CI: 55-77) in central and northern Europe (p=0.002). This geographical variation remained after adjustment for other risk factors. An increasing number of years of sexual activity (p=0.0002) and a history of prostitution (p=0.0001) were independently associated with HSV-2 prevalence. In HSV-2 positive women, symptomatic cases of HSV infection were minimal, but increased with decreasing CD4 count. Conclusion: In HIV infected women, the prevalence of HSV antibodies is high and symptomatic cases of HSV infection are minimal, but increase with decreasing CD4 count. HSV-2 but not HSV-1 was related to sexual behaviour (that is, a history of prostitution and the number of sexually active years) in this group of HIV infected women

Cesarean-section and Risk of Vertical Transmission of Hiv-1 Infection

Indirect evidence suggests that a significant proportion of vertical transmission of HIV infection occurs late in pregnancy or during delivery. Caesarean section, therefore, may protect the fetus from infection. We looked at 1254 HIV-infected mothers and their children and the effects of different modes of delivery on transmission risk. We also included a detailed assessment of confounding factors associated with transmission risk. Women who had caesarean sections were more advanced in their disease progression which may cause the protective effect of caesarean section to be underestimated. When this and other potential confounding factors were taken into account, caesarean section was estimated to halve the rate of transmission. This finding is important in the design of studies to evaluate treatments aimed at reducing mother-to-child transmission

Vertical transmission of HIV-1: Maternal immune status and obstetric factors

Objective: To estimate the effect of maternal factors and events around the time of delivery on HIV-1 vertical transmission risk. Design: Prospective study. Setting: Twenty-two obstetric and paediatric clinics in seven European countries. Patients or other participants: Mothers identified as HIV-infected before or at delivery and their children. Main outcome measure: Paediatric HIV infection. Results: By November 1995, 1846 mothers with 1945 children had been enrolled. The vertical transmission rate was 16.4% (95% confidence interval, 14.5-18.3). Parity, maternal age, race, mode of HIV acquisition, injecting drug use and sex of infant were not statistically significantly associated with risk of transmission, Children delivered vaginally were more likely to be infected than those delivered by Caesarean section. However, in vaginal deliveries the procedures used, duration of ruptured membranes or length of second-stage labour were not related to transmission. Transmission increased almost linearly with decreasing CD4 cell count, but there was no such trend for CD8 cell count. Women with CD4 cell counts below 200 x 10(6)/l were significantly more likely to deliver early (chi(2) for trend, 14.02; P < 0.001). Very premature infants were at increased risk of infection, but after about 35 weeks gestation the transmission rate remained stable, with no increase in late pregnancy. This trend was confirmed after allowing for maternal CD4 cell count. Conclusions: The rate of vertical transmission increases linearly with decreasing maternal CD4 cell count. Women with fewer than 200 x 10(6) CD4 cells/l have an increased risk of premature delivery, which would affect timing of interventions. The stable transmission rate after 35 weeks gestation suggests little acquisition of infection during late pregnancy

Perinatal Findings In Children Born To Hiv-infected Mothers

Objective To explore in children born to HIV-infected women, the association between a child's HIV infection status and birthweight, gestational age, congenital abnormalities and other perinatal findings. Design A prospective study of children born to women known to be HIV-infected at or before the time of delivery enrolled in the European Collaborative Study. Setting Nineteen European centres. Subjects A cohort of 853 children with known HIV infection status. Results There was no evidence for an HIV dysmorphic syndrome, and the frequency of congenital abnormalities was similar in infected and uninfected children with no consistent pattern of defects. Injecting drug use during pregnancy had the most marked effect on birthweight and gestational age. Multivariate analysis demonstrated a weak association between birthweight and the child's HIV infection status, but this could partly be explained by the confounding effect of maternal immunological HIV status. HIV infection in the infant was not associated with gestational age, and the mean and distribution of gestational age were similar for infected and noninfected children. Conclusions The finding that HIV-infected and noninfected children are of similar birthweight, the absence of a dysmorphic syndrome and no evidence of associated congenital abnormalities suggest that a substantial proportion of infection occurs late in pregnancy or at the time of delivery

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

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