Serena Dalzero

Antiretroviral treatment in pregnancy: a six-year perspective on recent trends in prescription patterns, viral load suppression, and pregnancy outcomes.

The aim of the study was to describe the recent trends in antiretroviral treatment in late pregnancy and the sociodemographic changes among pregnant women with HIV over the last 6 years. Data from the National Program on Surveillance on Antiretroviral Treatment in Pregnancy in Italy were grouped per calendar year, and changes in antiretroviral treatment, population characteristics, maternal immunovirologic status and newborn clinical parameters were analyzed. A total of 981 HIV-infected mothers who delivered between 2002 and 2008 were evaluated. The proportion of women receiving at least three antiretroviral drugs at delivery increased significantly from 63.0% in 2002 to 95.5% in 2007-2008, paralleled by a similar upward trend in the proportion of women who achieved complete viral suppression at third trimester (from 37.3 in 2002 to 80.9 in 2007-2008; p < 0.001). The co-formulation of zidovudine plus lamivudine remained the most common nucleoside backbone in pregnancy, even if a significant increase in the use of tenofovir plus emtricitabine was observed in more recent years. Starting from 2003, nevirapine prescription declined, paralleled by a significant rise in the use of protease inhibitors (PI), which were present in more than 60% of regimens administered in 2007-2008. Nelfinavir was progressively replaced by ritonavir-boosted PIs, mainly lopinavir. No significant changes in preterm delivery, Apgar score, birth weight, and birth defects were observed during the study period, and the rate of HIV transmission remained below 2%. These data demonstrate a significant evolution in the treatment of HIV in pregnancy. Constant improvements in the rates of HIV suppression were observed, probably driven by the adoption of stronger and more effective regimens and by the increasing options available for combination treatment.

Voluntary pregnancy termination among women with HIV in the HAART era (2002-2008): a case series from a national study.

Abstract There is limited information about the determinants of voluntary pregnancy termination (VPT) among women with HIV in the current context of wide access to highly active antiretroviral therapy (HAART). To investigate this issue, we analysed the characteristics of a series of VPTs which occurred in an ongoing observational national study of pregnant women with HIV between 2002 and 2008. Sixty-three cases of VPT were compared with 334 pregnancies not ending in a VPT concurrently reported from the same centres. VPTs showed significant associations with unplanned pregnancy (odds ratio [OR]: 24.3; 95% confidence interval [CI]: 5.8–101.2), previous pregnancies reported to the study (OR: 2.5; 95% CI: 1.30–4.82), lower CD4 counts (270 vs. 420 cells/mm3), and HIV-infected current partner (OR: 1.88; 95% CI: 0.97–3.63). Our data indicate that there is still the need to improve pregnancy planning among women with HIV, and strongly suggest that interventions aimed at improving pregnancy planning might also reduce the occurrence of VPT. Women with low CD4 counts and those with an HIV-infected partner represent two groups that should receive particular attention in preventive strategies.

Lipid Profile During Pregnancy in HIV-Infected Women

Abstract Purpose: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. Method: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (PIs) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. Results: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p .001), 60.8 mg/dL for total cholesterol (p .001), 13.7 mg/dL for HDL cholesterol (p .001), and 17.8 mg/dL for LDL cholesterol (p = .001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on PIs. The effect of PIs on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. Conclusion: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV.

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.

Pregnancy Outcomes in Women with Advanced HIV Infection in Italy

Pregnancy has been associated with a low risk of HIV disease progression. Most pregnancies with HIV currently involve women who have not experienced AIDS-defining events, and are clinically classified as Centers for Disease Control and Prevention (CDC) groups A or B. We evaluated the main maternal outcomes among pregnant women with more advanced HIV disease, defined by CDC-C disease stage. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. A total of 566 HIV-infected mothers, 515 in stage A or B (CDC-AB group) and 51 in stage C (CDC-C group) were evaluated. The two groups had similar baseline characteristics. No differences were found in the main maternal and neonatal outcomes. Most of the women achieved viral suppression at end of pregnancy (>1000 copies per milliliter: CDC-C: 17.2%; CDC-AB: 13.7%). One year after delivery, HIV replication (HIV-RNA >1000 copies per milliliter) was present in 11.5% of CDC-AB women and 30.0% CDC-C women. Despite lower initial CD4 counts (300 versus 481 cells per microliter), CDC-C women maintained stable CD4 levels during pregnancy, and 1 year after delivery, a significant increase in CD4 count from preconception values was observed in both groups (CDC-C: +72 cells per microliter, p=0.031; CDC-AB: +43 cells per microliter, p<0.001). Only one AIDS event occurred in a woman with a previous diagnosis of AIDS. In CDC-C women, pregnancy is not associated with an increased rate of adverse maternal or neonatal outcomes, and a good immunovirologic response can be expected. During postpartum care, women with more advanced HIV infection should receive particular care to prevent loss of virologic suppression.

Rate, Predictors, and Consequences of Late Antenatal Booking in a National Cohort Study of Pregnant Women With HIV in Italy

Abstract Objective: To evaluate the prevalence and consequences of late antenatal booking (13 or more weeks gestation) in a national observational study of pregnant women with HIV. Methods: The clinical and demographic characteristics associated with late booking were evaluated in univariate analyses using the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. The associations that were found were re-evaluated in multivariable logistic regression models. Main outcomes were preterm delivery, low birthweight, nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV plasma viral load at third trimester, delivery complications, and gender-adjusted and gestational age-adjusted Z scores for birthweight. Results: Rate of late booking among 1,643 pregnancies was 32.9%. This condition was associated with younger age, African provenance, diagnosis of HIV during pregnancy, and less antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%, P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of delivery were more common with late booking (8.2% vs 5.0%, P = .013). Multivariable analyses confirmed an independent role of late booking in predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7; 95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8; P = .005). Conclusions: Late antenatal booking was associated with detectable HIV RNA in late pregnancy and with complications of delivery. Measures should be taken to ensure an earlier entry into antenatal care, particularly for African women, and to facilitate access to counselling and antenatal services. These measures can significantly improve pregnancy management and reduce morbidity and complications in pregnant women with HIV.

Pregnancy Outcomes in HIV-Infected Women of Advanced Maternal Age

Abstract Background: There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age.Methods: Data from a national observational study in Italy were used to evaluate the risk of nonelective cesarean section, preterm delivery, low birthweight, major birth defects, and small gestational age-adjusted birthweight according to maternal age (<35 and ≥35 years, respectively).Results: Among 1,375 pregnancies with live births, 82.4% of deliveries were elective cesarean sections, 15.8% were nonelective cesarean sections, and 1.8% were vaginal deliveries. Rates of nonelective cesarean section were similar among mothers ≥35 and <35 years (odds ratio [OR], 1.22; 95% CI, 0.90–1.65;P = .19). Preterm delivery and low birthweight were significantly more common among women ≥35 years in univariate but not in multivariate analyses. Newborns from women ≥35 and <35 years showed no differences inZ scores of birthweight, with a similar occurrence of birthweight <10th percentile (12.1% vs 12.0%; OR, 1.02; 95% CI, 0.71–1.46;P = .93). The overall rate of birth defects was 3.4% (95% CI, 2.4–4.4), with no differences by maternal age (≥35 years, 3.5%; <35 years, 3.3%; OR, 1.05; 95% CI, 0.56–1.98;P = .88).Discussion: In this study of pregnant women with HIV, older women were at higher risk of some adverse pregnancy outcomes, such as preterm delivery and low birthweight. The association, however, did not persist in multivariable analyses, suggesting a role of some predisposing factors associated with older age.

Declining HCV seroprevalence in pregnant women with HIV

We assessed recent trends in hepatitis C virus (HCV) prevalence in pregnant women with HIV using data from a large national study. Based on 1240 pregnancies, we observed a 3.4-fold decline in HCV seroprevalence in pregnant women with HIV between 2001 (29.3%) and 2008 (8.6%). This decline was the net result of two components: a progressively declining HCV seroprevalence in non-African women (from 35.7% in 2001 to 16.7% in 2008), sustained by a parallel reduction in history of injecting drug use (IDU) in this population, and a significantly growing presence (from 21.2% in 2001 to 48.6% in 2008) of women of African origin, at very low risk of being HCV-infected [average HCV prevalence 1%, adjusted odds ratio (aOR) for HCV 0.09, 95% CI 0.03-0.29]. Previous IDU was the stronger determinant of HCV co-infection in pregnant women with HIV (aOR 30.9, 95% CI 18.8-51.1). The observed trend is expected to translate into a reduced number of cases of vertical HCV transmission.

HPV Infection in a Cohort of HIV-Positive Men and Women: Prevalence of Oncogenic Genotypes and Predictors of Mucosal Damage at Genital and Oral Sites.

The aim of this study was to assess the prevalence of HPV infection and determinants of abnormal cytology in HIV-positive patients. In a cross-sectional study, patients of both sexes, asymptomatic for HPV, underwent anorectal (men)/cervical (women) and oral swabs. Cytology and HPV-PCR detection/genotyping (high- and low-risk genotypes, HR-LR/HPV) were performed. A total of 20% of the 277 enrolled patients showed oral HPV, with no atypical cytology; in men, anal HPV prevalence was 81% with 64% HR genotypes. In women, cervical HPV prevalence was 58% with 37% HR-HPV. The most frequent genotypes were HPV-16 and HPV-18; 37% of men and 20% of women harbored multiple genotypes. Also, 47% of men showed anal squamous intraepithelial lesions (SILs); 6% had high- and 35% low-grade SILs (HSILs/LSILs); 5% had atypical squamous cells of undetermined significance (ASC-US). HR-HPV was independently associated with anal-SIL in men (P = 0.039). Moreover, 37% of women showed cervical SIL: 14 ASC-US, 15 LSILs, 4 HSILs, and 1 in situ cancer. The presence of both LR and HR-HPV in women was independently associated with SIL (P = 0.003 and P = 0.0001). HR-HPV and atypical cytology were frequently identified in our cohort. HPV screening should be mandatory in HIV-infected subjects, and vaccine programs for HPV-negative patients should be implemented.

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.