Anna Bucceri

Polymerase chain reaction, virus isolation and antigen assay in HIV-1-antibody-positive mothers and their children

Diagnosis of perinatal HIV-1 infection is complicated by the persistence of maternal antibodies and the conflicting reports on polymerase chain reaction (PCR) reactivity in children born to HIV-1-seropositive mothers. We have compared PCR with other diagnostic methods for perinatal HIV-1 infection and have attempted also to identify maternal markers which correlate with risk of transmission. PCR was the most sensitive method for early diagnosis of perinatal transmission of HIV-1, but the PCR-positive children (n = 11) developed at least one additional sign of infection. The PCR-negative children (n = 76) were clinically healthy, virus isolation negative, and their serum was HIV-1-antigen-negative. All children who had become seronegative (n = 36) were both PCR- and isolation-negative. Antigenaemia in the mothers correlated significantly with higher risk of perinatal transmission of HIV-1, while no other parameters (clinical stage, lymphocyte subsets, PCR and isolation) showed such a correlation. This indicates that the level of virus expression may be of key importance for the risk of vertical transmission of HIV-1 infection.

Mode of delivery and gestational age influence perinatal HIV-1 transmission

Some data suggest that cesarean section reduces mother-to-child HIV-1 transmission. To assess the influence of mode of delivery and other maternal and infant factors on the rate of transmission, we analyzed the data of 1,624 children prospectively followed from birth. Of these, at the last visit 1,033 were > 18 months of age or would have been had they not died of HIV-related illness. Among the 975 first singleton children, 180 [18.5%; 95% confidence limits (CL), 16.1-20.9] acquired infection, as did 8 of 56 (14.3%; 95% CL, 5.1-23.5) second-born children. Multivariate stepwise analysis showed that vaginal delivery and development of symptoms in the mother were significantly and independently associated with a higher transmission rate (vaginal delivery; odds ratio, 1.69; 95% CL, 1.14-2.5; symptoms: odds ratio, 1.61; 95% CL, 1.12-2.3). In contrast, a history of maternal drug use, birth weight, breast-feeding (only 37 infants were breast-fed), and childs sex did not have a significant impact on viral transmission. The percentage of infected children was highest (30.7%) among very premature infants (< or = 32 weeks of gestation); this significant trend subsequently decreased to 11.9% at the week 42 (p < 0.001), suggesting a parallel reduction in peripartum transmission. The reduced rate of infection observed in infants born by cesarean section underlines the urgent need for randomized controlled trials to evaluate the protective role of surgical delivery in preventing perinatal HIV-1 transmission.

Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy The Italian Register for HIV Infection in Children*

OBJECTIVE To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine (ZDV) monotherapy in pregnancy. DESIGN Observational retrospective study of a prospectively recruited cohort. SETTING Italian Register for HIV Infection in Children. PATIENTS A group of 216 children perinatally infected with HIV-1, born in 1992-1997 and derived prospectively from birth: 38 children had mothers receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy. MAIN OUTCOME MEASURES The estimated probability of developing severe disease or severe immune suppression, survival probability [95% confidence interval (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatments (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral therapy before the onset of severe disease, severe immune suppression or death) were compared. RESULTS Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [57.3% (95% CI 40.9-74.3) versus 37.2% (95% CI 30.0-45.4); log-rank test 7.83, P = 0.005; adjusted hazard ratio 1.8 (95% CI 1.1-3.1)] or severe immune suppression [53.9% (95% CI 36.3-73.5) versus 37.5% (95% CI 30.0-46.2); log-rank test 5.58, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower survival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank test 4.23, P = 0.039; adjusted hazard ratio of death 1.9 (95% CI 1.1-3.6)]. CONCLUSIONS This epidemiological observation could stimulate virologic studies to elucidate whether this rapid progression depends on in utero infection or transmission of resistant virus. Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected.

Pregnancy outcome among HIV positive and negative intravenous drug users

OBJECTIVE To analyze determinants of pregnancy outcome, among HIV infected and uninfected intravenous drug users. STUDY DESIGN A total of 315 pregnant current intravenous drug users, IVDU (151 HIV infected and 164 HIV uninfected subjects) were referred to the Center for Pregnant Drug Addicts of the Mangiagalli Clinic, Milan, Italy, for internatal care and delivery between 1985 and 1993. RESULTS HIV uninfected and infected mothers did not differ significantly according to type of pregnancy, gestational age at childbirth, mode of delivery, pregnancy outcome and newborn weight, height, head circumference, sex and Apgar at 1 and 5 min. Out of 133 children (born to HIV infected mothers) for whom HIV status was available, 20 (15%) were HIV infected or developed AIDS-related signs and symptoms during a 24 months follow-up. The distribution of HIV infected and non infected infants was not significantly different as regards maternal CD4 lymphocyte count, week of gestation at birth, mode of delivery, infant weight, height, head circumference and Apgar at 1 and 5 min. CONCLUSION Our data show that HIV infected women in the early stages of HIV infection are not at a higher risk of adverse course of pregnancy than HIV uninfected women. Vertical transmission rates were not associated to newborn characteristics.

Perinatal Outcome in HIV-Infected Pregnant Women

We have observed 74 HIV-seropositive and 48 HIV-seronegative drug-addicted women and 22 HIV-seropositive nondrug-addicted pregnant women during pregnancy and we report their perinatal outcome. 8 out of 96 HIV-seropositive patients had hematological signs of immunodeficiency and 2 of these patients were symptomatic belonging to CDC class III. We recorded 2 early and 3 late spontaneous abortions, no intrauterine fetal death and 3 neonatal deaths. Seropositive patients had 3 malformed babies, seronegative patients had 1. All these women had a high incidence of premature delivery and intrauterine fetal growth retardation: seropositive patients had a higher incidence of fetuses small for gestational age and a lower incidence of preterm delivery compared to seronegative patients, but the difference was not statistically significant. The incidence of malformation was comparable to the general population: 3 malformed babies were born to HIV-positive drug-addicted mothers, and 1 to a seronegative drug-addicted mother. These findings do not support the hypothesis of a direct detrimental effect of HIV on perinatal outcome. Consequences of fetal exposure to maternal HIV infection involve mostly postnatal life and development of acquired immunodeficiency.

Early invasive diagnostic techniques during pregnancy in HIV-infected women

Current counseling to HIV-infected pregnant women tends to discourage second trimester amniocentesis or other early prenatal invasive procedures because of the possible iatrogenic risk of mother-to-child transmission of the virus. This recommendation is based on scant epidemiological evidence deduced from studies conducted primarily before the widespread use of zidovudine for the prevention of perinatal transmission and mostly referring to antenatal sampling techniques performed in the last trimester of pregnancy. Tess et al. reported that six out of 15 women who underwent third trimester amniocentesis had infected newborns (OR, 4.1; 95% CI, 1.2–13.5) (1). Mandelbrot et al. discovered a 36% vertical transmission among 39 invasive procedures (26 amnioscopies and 13 amniocenteses or other needling maneuvers) while the Pediatric AIDS Clinical Trials Group protocol 076 reported that five out of nine non-treated women who underwent amniocentesis delivered an infected infant compared to none among five zidovudine-treated women (2, 3). However, in both these two latest studies gestational age at the time of the procedure was not indicated. Specific reports on antenatal sampling performed in the second trimester are yet to be made available. Thus, for the moment, there ap-

Treatment change in pregnancy is a significant risk factor for detectable HIV-1 RNA in plasma at end of pregnancy.

Abstract Purpose: To investigate the risk factors for an HIV-1 RNA plasma viral load above 400 copies/mL in the third trimester of pregnancy. Methods: Data from a large national study were used. The possible determinants were assessed in univariate analyses and in a multivariate logistic regression model in order to adjust for possible confounders. Results: Among 662 pregnancies followed between 2001 and 2008, 131 (19.8%) had an HIV-1 plasma copy number above 400/mL at the third trimester of pregnancy. In the multivariate analysis, the variables significantly associated with this occurrence were earlier calendar year (adjusted odds ratio [AOR] per additional calendar year, 0.70; 95% CI, 0.63–0.77; P < .001), lower CD4 count at enrollment (AOR per 100 cells lower, 1.18; 95% CI, 1.09–1.27; P < .001), HIV-1 RNA levels above 400 copies per mL at enrollment (AOR, 2.23; 95% CI, 1.50–3.33; P < .001), and treatment modification during pregnancy (AOR, 1.66; 95% CI, 1.07–2.57; P = .024). Conclusions: Treatment changes in pregnancy significantly increase the risk of an incomplete viral suppression at the end of pregnancy. In HIV-infected women of childbearing age, proper preconception care, which includes the preferential prescription of regimens with the best safety profile in pregnancy, is likely to prevent an incomplete viral suppression at the end of pregnancy.

Factors influencing gestational age-adjusted birthweight in a national series of 600 newborns from mothers with HIV

Abstract Background: Few studies have assessed the determinants of birthweight in newborns from HIV-positive mothers in analyses that adjusted for different gestational age at delivery. Method: We calculated gestational age-adjusted birthweight Z-score values in a national series of 600 newborns from women with HIV and in 600 newborns from HIV-negative women matched for gender and gestational age. The determinants of Z-score values in newborns from HIV-positive mothers were assessed in univariate and multivariate regression analyses. Results: Compared to newborns from HIV-negative women, newborns from HIV-positive women had significantly lower absolute birthweight (2799 vs. 2887 g; p = .007) and birthweight Z score (−0.430 vs. −0.222; p < .001). Among newborns from mothers with HIV, the maternal characteristics associated with significantly lower Z-score values in univariate analyses were recent substance use (Z-score difference [ZSD] 0.612, 95% CI 0.359−0.864, p < .001), smoking >10 cigarettes/day (ZSD 0.323, 95% CI 0.129−0.518, p = .001), absence of pregnancies in the past (ZSD 0.200, 95% CI 0.050−0.349, p = .009), no antiretroviral treatment in the past (ZSD 0.186, 95% CI 0.044−0.327, p = .010), and Caucasian ethnicity compared to Hispanic (ZSD 0.248, 95% CI 0.022−0.475, p = .032). Body mass index (BMI) at conception and maternal glycemia levels during pregnancy were also significantly related to birthweight Z scores. Glycemia, BMI, and recent substance use maintained a significant association with Z-score values in multivariate analyses. In the multivariate analysis, the only factors significantly associated with Z-score values below the 10th percentile were recent substance use (adjusted odds ratio [AOR] 3.17, 95% CI 1.15−8.74) and smoking (AOR 2.26, 95% CI 1.13−4.49). Discussion: We identified several factors associated with gestational age-adjusted birthweight in newborns from women with HIV. Smoking and substance use have a significant negative impact on intrauterine growth, which adds to an independent HIV-related effect on birthweight. Prevention and information on this issue should be reinforced in women with HIV of childbearing age to reduce the risk of negative outcomes in their offspring.

Pregnancy outcomes and antiretroviral treatment in a national cohort of pregnant women with HIV: overall rates and differences according to nationality.

We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001–06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women.

Glucose Plasma Levels and Pregnancy Outcomes in Women with HIV

Abstract Background: There is limited information on the relation between glucose levels in pregnancy and adverse perinatal outcomes in HIV-infected pregnant women. Objective: To evaluate the potential impact of fasting glucose levels on pregnancy outcomes in a large sample of pregnant women with HIV from a national study, adjusting for potential confounders. Methods: Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. The main outcomes evaluated in univariate and multivariable analyses were birthweight for gestational age >90th percentile (large for gestational age [LGA]), nonelective cesarean delivery, and preterm delivery. Glucose measurements were considered both as continuous and as categorical variables, following the HAPO study definition. Results: Overall, 1,032 cases were eligible for the analysis. In multivariable analyses, a birthweight >90th percentile was associated with increasing fasting plasma glucose levels (adjusted odds ratio [AOR] per unitary (mg/dL) increase, 1.04; 95% CI, 1.01–1.06; P = .005), a higher body mass index, and parity of 1 or higher. A lower risk of LGA was associated with smoking and African ethnicity. A higher fasting plasma glucose category was significantly associated with LGA occurrence, and AORs for the glucose categories of 90–94 mg/ dL and 95–99 mg/dL were 3.34 (95% CI, 1.09–10.22) and 6.26 (95% CI, 1.82–21.58), respectively. Fasting plasma glucose showed no association with nonelective cesar-ean section [OR per unitary increase, 1.00; 95% CI, 0.98–1.02] or preterm delivery [OR per unitary increase, 1.00; 95% CI, 0.99–1.02]. Conclusions: In pregnant women with HIV, glucose values below the threshold usually defining hyperglycemia are associated with an increased risk of delivering LGA infants. Other conditions may independently contribute to adverse perinatal outcomes in women with HIV and should be considered to identify pregnancies at risk.