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 zidovudinel; 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% Cl, 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. (c) 2006 Lippincott Williams & Wilkins.

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 deliveries.

ObjectiveTo describe changes over a 15-year period in characteristics and management of HIV-infected pregnant women in Europe. DesignProspective study. MethodsAnalysis of prospective data on 2876 pregnant HIV-infected women and their 3076 infants. Factors examined included maternal socio-demographic, immunological and virological characteristics, antiretroviral therapy and pregnancy outcome. ResultsAmong women enrolled, the proportion with heterosexual acquisition of infection has increased significantly from 59% (201/342) in 1985–1987 to 69% (327/471) after 1997 while the proportion acquiring HIV through injecting drug use has declined. Overall median CD4 cell count was 440 × 106/l and 41% of women had undetectable viral load at delivery. In 1995 28% (72/256) of mother–child pairs received the full 076 regimen to reduce risk of vertical transmission, rising significantly to 89% (116/130) by 1999. Use of triple therapy started in pregnancy has increased significantly from < 1% (1/153) in 1997 to 44% (47/107) in 1999. Exposure to antiretroviral therapy was not associated with prevalence or pattern of congenital abnormalities (P = 0.88) but was associated with reversible anaemia in the infant (P < 0.002). The elective cesarean section rate has increased from 10% in 1992 to 71% in 1999/2000. The vertical transmission rate declined from 15.5% by 1994 to 2.6% after 1998. In multivariate analysis, adjusting for maternal CD4 cell count, risk of vertical transmission was reduced by 66% (95% confidence interval, 37–82%) with the full 076 regimen and by 60% (95% confidence interval, 33–73%) with elective cesarean section delivery. ConclusionsChanges in treatment of adult HIV disease have affected the management of infected pregnant women. Despite therapeutic and surgical interventions, vertical transmission still occurs.

Objective: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV.Design: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis.Methods: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded.Results: The primary analysis included 4721 deliveries with duration of ruptured membranes less than or equal to 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01).Conclusions: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes. (C) 2001 Lippincott Williams & Wilkins.

ObjectiveTo assess the association between type and timing of initiation of antiretroviral therapy in pregnancy and duration of pregnancy. DesignProspective study. MethodsData 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. ResultsThe 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). ConclusionsPregnancy 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.

In order to analyse temporal trends in vertical transmission rates of human immunodeficiency virus (HIV) and determinant of congenital HIV infection in Italy, we have considered data from a network of hospitals co-operating in the Italian Collaborative Study on HIV infection in pregnancy, conducted between 1988 and 1995, A total of 1040 women entered the study. The HIV-1 status of the babies was known in 848 cases (81.5%). Transmission rates were highest in the period 1988-1991, then tended to decrease and in 1995 the rate was 9.7 per 100 children (this finding, however, was based on only six infected children and the trend was not statistically significant). Considering the overall series, the risk of vertical HIV transmission was higher in women with low CD4 count in pregnancy [odds ratio (OR) <400 versus greater than or equal to 400 1.8, 95% confidence interval (CI) 1.1-2.9], In comparison with vaginal delivery the risk of transmission was 0.3 (95% CI 0.1-0.5) and 0.6 (95% CI 0.3-1.2) respectively for elective and emergency delivery, In comparison with women who delivered at term (greater than or equal to 37 gestation weeks) the OR of HIV infection of the babies for the whole series was 2.2 (95% CI 1.3-3.6) in women who delivered preterm, Similar findings emerged when the analysis was conducted considering, separately, subjects observed in the period 1988-1991 and 1992-1995, The frequency of Caesarean section increased from 26.5% of deliveries in 1988-1991 to 36.2% in 1992-1995. Consequently, most temporal differences disappeared after standardization for mode of delivery, but the rate in 1995 was still lower than in 1988-1994.

Objective: Prophylactic zidovudine during pregnancy and labour reduces maternal viral load and, with neonatal therapy, has been shown to reduce vertical transmission. However, zidovudine may have additional effects. Advanced HIV disease is associated with premature delivery, which in turn results in increased vertical transmission. Data from the European Collaborative Study (ECS) were analysed to investigate whether zidovudine could be associated with decreased prematurity risk and/or with a reduced frequency of low birthweight.Methods: HIV-infected pregnant women enrolled in the ECS were followed prospectively according to a standard protocol. Gestational age was assessed by ultrasound, prematurity was defined as delivery before 37 weeks and the cut-off for low birthweight was 2500 g. We calculated odds ratios (OR) to estimate the effect of zidovudine on the risk of premature or low birthweight delivery.Results: In 2299 mothers, zidovudine taken to reduce the risk of vertical transmission decreased the odds of premature delivery by a quarter (OR = 0.76, 95% confidence interval (CI) 0.53-1.09), and the odds of low birthweight by nearly half (OR = 0.55, 95% CI 0.39-0.79). Allowing for CD4 count and mode of delivery did not greatly alter these OR values. A multivariate analysis suggested that prophylactic zidovudine and prematurity were independently associated with risk of transmission.Conclusion: Our findings suggest an additional health benefit of zidovudine. Even ii most vertical transmission occurs around the time of delivery, therapy earlier in pregnancy could have an indirect effect on transmission rates through delaying delivery. This hypothesis needs to be confirmed or refuted by more appropriate studies.

Background Results from observational studies suggest that caesarean-section delivery may reduce the risk of mother-to-child transmission of HIV-1 infection in comparison with vaginal delivery. We carried out a randomised clinical trial to address this issue and to assess the extent of postdelivery complications.Methods Eligible women were between 34 and 36 weeks of pregnancy, with a confirmed diagnosis of HIV-1 infection, and without an indication for caesarean-section delivery or a contraindication to this mode of delivery. Women were randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or vaginal delivery. An infant was classified as uninfected if he or she became negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR or culture on at least two occasions, with no clinical, immunological, or viral evidence of infection. From 1993, to March, 1998, 436 women were randomised.Findings We present the results of an analysis updated to November, 1998, with data on the infection status of 370 infants. Three (1.8%) of 170 infants born to women assigned caesarean-section delivery were infected, compared with 21 (10.5%) of 200 born to women assigned vaginal delivery (p<0.001). Seven (3.4%) of 203 infants of women who actually gave birth by caesarean section were infected compared with 15 (10.2%) of 167 born vaginally (p=0.009). There were few postpartum complications and no serious adverse events in either group.Interpretation Our findings provide evidence that elective caesarean-section delivery significantly lowers the risk of mother-to-child transmission of HIV-1 infection without a significantly increased risk of complications for the mother.

Objective: To examine immunological markers in HIV-infected pregnant women. Design: Women enrolled in the European Collaborative Study and the Swiss HIV Pregnancy Cohort were followed throughout pregnancy according to similar clinical and immunological protocols. Information was recorded at various times during pregnancy and, in some centres, also 6 weeks and 6 months post-partum. Method: Locally-weighted linear regression analysis was used to investigate changes in markers of cellular and humoral immune function during pregnancy and immediately post-partum, taking into account the serial measurement data structure. Women who received zidovudine during pregnancy were excluded. Results: Four hundred and thirty-eight women had two or more measurements during pregnancy or within 6 months of delivery. Twenty-four per cent (106) of the women reported injecting drugs during pregnancy. Mean CD4 and CD8 cell counts declined to a low level 6 months before delivery, increased gradually until delivery and rose sharply to a peak level 3 months post-partum. In contrast, CD4 and CD8 percentages were stable during pregnancy, and increased slightly thereafter. The same pattern was evident for transmitting women, those delivered by Cesarean section, and women who injected drugs during pregnancy, and there was no evidence for an association with immunosuppression. Total immunoglobulin (Ig) G levels declined gradually throughout pregnancy until delivery, and increased in the 6 month post-partum period. Total IgM and IgA levels remained stable throughout pregnancy. Conclusions: These findings suggest that pregnancy does not accelerate HIV progression, but in view of the intrinsic variability in serial CD4 counts, caution should be exercised when assessing changes in immunological markers in individual pregnant women.

OBJECTIVE: To investigate epidemiologic, clinical and pathologic aspects of various grades of vulvar intraepithelial neoplasia (VIN).STUDY DESIGN: A retrospective, multicenter study of 370 cases of vulvar intraepithelial neoplasia (VIN) wits performed by the Italian Study Group on Vulvar Disease.RESULTS: Of the 370 cases, 148 were VIN 1 (40.0%), 53 were VIN 2 (14.3%), and 169 were VIN 3 (45.7%). The mean age of the patients was 52.6 years. During the study period an increase in the rate of human papillomavirus-associated VIN was observed. In addition, while VIN 1 and 2 were associated mostly with squamous cell hyperplasia, VIN 3 was almost equally associated with lichen sclerosus and squamous cell hyperplasia; the difference was statistically significant. Intraepithelial or invasive squamous neoplasia of the lower genital tract was associated in 22% of the cases (82/370).CONCLUSION The results of the investigation, although not allowing firm conclusions due to the retrospective and multicentered nature of the study, demonstrate the extreme heterogeneity of VIN lesions.

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 200×106/l were significantly more likely to deliver early (&khgr;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 200×106 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.

Brugnoni, D.; Prati, E.; Malacarne, F.; Gorla, R.; Airò, P.; Cataneo, R. Author Information

Peripheral blood lymphoid cell expansions with an unusual CD3+, CD4+, CD8dim+/-, CD11b+, CD57+ immunophenotype have recently been reported. They frequently have the morphology of large granular lymphocytes (LGL) and can be either monoclonal or polyclonal. Their significance is still unclear and no association with hematological neoplasms has been described. We report the case of a patient with a monoclonal expansion of LGL associated with a B-cell-derived hairy cell leukemia. The two lymphoid clones were not physically associated since T-LGL were found in the peripheral blood and hairy cells were detected in the bone marrow and kidney.