Atazanavir and darunavir in pregnant women with HIV: evaluation of laboratory and clinical outcomes from an observational national study.

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results: Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P < 0.001). Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelines showed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in terms of main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribing physicians might prefer either drug in some particular situations where the different impacts of treatment on lipid profile and bilirubin may have clinical relevance.

Rate, correlates and outcomes of repeat pregnancy in HIV-infected women.

OBJECTIVES: The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. METHODS: Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. RESULTS: The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio (OR) 1.36; 95% confidence interval (CI) 1.10-1.68], diagnosed with HIV infection in the current pregnancy (OR: 1.69; 95% CI: 1.35-2.11), and at their first pregnancy (OR: 1.33; 95% CI: 1.06-1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/µL), with almost no clinical progression to Centers for Disease Control and Prevention stage C (CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). CONCLUSIONS: Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies.

Pregnant with HIV before age 25: data from a large national study in Italy, 2001-2016.

Young pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001-2016, 9·0% were in women <25 years, with a significant increase over time (2001-2005: 7·0%; 2006-2010: 9·1%; 2011-2016: 12·2%, P < 0·001). Younger women had a lower rate of planned pregnancy (23·2% vs. 37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36-0·69), were more frequently diagnosed with HIV in pregnancy (46·5% vs. 20·9%, OR 3·29, 95% CI 2·54-4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (<25 years: 56·3%; ⩾25 years: 69·0%, OR 0·58, 95% CI 0·41-0·81). During pregnancy, treatment coverage was almost universal in both age groups (98·5% vs. 99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series.

OBJECTIVES: To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. DESIGN: Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. SETTING: University and hospital clinics. POPULATION: Pregnant women with HIV. METHODS: Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. MAIN OUTCOME MEASURES: Rate of invasive testing, intrauterine death, HIV transmission. RESULTS: Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011-2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. CONCLUSIONS: The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. TWEETABLE ABSTRACT: No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens.

HCV-HIV coinfected pregnant women: data from a multicentre study in Italy.

PURPOSE: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.

Rate, predictors, and consequences of late antenatal booking in a national cohort study of pregnant women with HIV in Italy.

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.

Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001-2011.

OBJECTIVE: We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. DESIGN: Observational study. SETTING: University and hospital clinics. POPULATION: Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. METHODS: The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. MAIN OUTCOME MEASURES: Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. RESULTS: A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9-4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9-4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51-1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51-1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56-2.55; protease inhibitors, OR 0.92, 95% CI 0.43-1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). CONCLUSIONS: This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities.

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.

Women facing HIV. Key question on women with HIV infection: Italian consensus workshop.

A panel of leading Italian specialists in infectious diseases, obstetrics and gynaecology met in a national consensus workshop on women facing HIV to review critical aspects and discuss recommendations for selected key questions on four issues: (1) women and highly active antiretroviral therapy (HAART): access to care and adherence to therapy, side effects and drug-drug interaction; (2) HIV-infected pregnant women: prevention of mother to child transmission; (3) desire for children among women living with HIV: assisted reproduction; (4) sexually transmitted diseases and genital disturbances. The method of a nominal group meeting was used, and recommendations were graded for their strength and quality of evidence using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed, and some of the most recent data supporting recommendations are provided.

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.

Lipid profile during pregnancy in HIV-infected women.

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.

The incidence of complications after caesarean section in 156 HIV-positive women.

OBJECTIVE: To investigate the risks of post-operative complications in HIV-positive mothers who undergo a caesarean section (CS) because the delivery cannot be safely accomplished by the vaginal route or to protect the infant from viral infection. DESIGN: In a multicentre study, we reviewed the incidence and type of post-operative complications in 156 HIV-positive women who underwent a CS. These results were compared with those observed in an equal number of HIV-uninfected women who matched for the indication requiring a caesarean delivery, the stage of labour, the integrity or rupture of membranes, and the use of antibiotic prophylaxis. SETTING: Seven teaching hospitals providing obstetrical care for mothers infected with HIV. RESULTS: We found that six HIV-infected mothers suffered a major complication (two cases of pneumonia, one pleural effusion, two severe anaemia and one sepsis) compared with only one HIV-negative woman who required blood transfusion after surgery. Minor complications like post-operative fever, endometritis, wound and urinary tract infections were significantly more frequent in HIV-positive women than controls. Multivariate analysis revealed that in HIV-infected women the only factor associated with a significant increase in the rate of complications was a CD4 lymphocyte count < 200 x 10(6)/l. CONCLUSIONS: The results of our study indicate that HIV-positive mothers are at an increased risk of post-operative complications when delivered by CS. The risk of post-operative complications is higher in HIV-infected women who are severely immunodepressed.

Maternal predictors of HIV vertical transmission.

We performed a retrospective study of 57 HIV-positive pregnant women and their children to look for maternal parameters related to rates of vertical transmission of HIV. Sixteen (28%) infants were HIV-infected. There was no positive correlation between maternal risk factors for HIV and vertical transmission of HIV. Multiparity seemed to be related to a higher prevalence of vertical transmission, whereas neither preterm delivery nor cesarean section resulted in different rates of vertical transmission, although they tended to have some protective effect. Maternal beta 2-microglobulin and serum neopterin levels were not related to different rates of vertical transmission of HIV. CD4+ cell counts did so only when cut-off values of 400/mm3 were taken. All the women in CDC group IV and all the HIV p24 antigen-positive transmitted the infection to their infants, whereas only 7/48 women in CDC groups II and III (P = 0.000006) and 9/48 HIV p24 antigen negative women (P = 0.00006) gave birth to infected infants. No other maternal characteristics were associated with different rates of vertical transmission in a multivariate analysis restricted to women in CDC groups II and III and with HIV p24 antigen negativity.

The changing HIV epidemic in Italian pregnant women.

OBJECTIVE: To describe changes in the characteristics of HIV-pregnant women in Italy and the impact of strategies for prevention of HIV vertical transmission. STUDY DESIGN: Since 1985, HIV-infected women and their children are followed in 23 European centres in the European Collaborative Study (ECS), according to a standard protocol. Eight Italian Obstetric units participating in the ECS enrolled 815 patients. RESULTS: Overall use of zidovudine to reduce HIV vertical transmission has increased significantly since 1994 and between 1995 and 1997, 57% of Italian women were treated. However, 27% of babies received the infant component of the 076 regimen. Over the years, age at delivery has increased and their CD4 count at delivery decreased, most likely reflecting heterosexually infected women with a longer duration of infection. The increasing rate of elective caesarean section (42%) is not related to maternal, foetal or obstetrical indications, but its use as an intervention to reduce HIV vertical transmission. CONCLUSIONS: The identification of HIV-infected women during pregnancy or before delivery ensures the appropriate management of the woman and her child, and clinicians should be aware of the increasing number of women with heterosexual acquisition of HIV-infection who may be less easily identified.

Does Helicobacter pylori eradication modify intestinal metaplasia evolution in the stomach?

BACKGROUND: We aimed to evaluate Helicobacter pylori eradication impact on the gastric carcinogenesis cascade following the evolution of intestinal metaplasia (IM) in gastric antrum after Helicobacter pylori (HP) eradication. METHODS: We followed yearly for a 5 year period after bacterial eradication, 69 HP positive patients with gastric or duodenal ulcers who showed antral gastric intestinal metaplasia at histology at time 0. All patients, eradicated by OAC triple short-term therapy and assessed both performing 13C-UBT 1 month after eradication and by Giemsa stain, persisted HP negative during follow-up. Upper endoscopy with 6 biopsies from gastric antrum at least 2 cm away from pylorus, was repeated every year in each patient involved in the study, in order to evaluate IM evolution and HP eradication persistence. During the follow-up histological specimens were examinated from the same pathologist and IM differentiated as complete (type I), incomplete (type II) or incomplete solphomucin-positive (type III). Statistical analysis between different groups after each year was performed by chi2 method. RESULTS: At time 0.48 cases out of 69 (69.7%) presented type I IM, 14 cases (20.2%) type II IM and 7 cases (10%) type III IM. IM presence in histological specimens after 1, 2, 3, 4 and 5 years from HP eradication were evaluated and statistical analysis between the 3 IM groups after each control showed a significant regression after HP eradication in type I versus III IM (p<0.001), mostly 2 and 3 years after HP eradication, but no significance in type I versus II IM (p=0.284) neither in type II versus III IM (p=0.981) also after 5 years. CONCLUSIONS: HP eradication permits complete intestinal metaplasia regression in gastric antrum 2 or 3 years after antibiotic treatment. Otherwise incomplete IM in gastric antrum, both type II and III, is not significantly modified after bacterial eradication.

Access to gynecological services and Papanicolau tests in HIV-infected Italian women: a questionnaire survey.

The objective of the study was to evaluate the access to Papanicolau (Pap) tests of HIV-infected women in Italy. A cross-sectional survey on a cohort of HIV-infected women seen at 27 HIV clinics was performed. At each clinic a female physician involved in the care of HIV-infected women was asked questions on clinic and patients' characteristics and on access to Pap tests. The outcome of the study was to find the percentage of women who had not had a Pap test before coming to the HIV clinic and the percentage having had a Pap test in 2001. In the survey, 7,600 HIV-infected women were represented. Women who came to the clinic without having ever had a Pap test were 62+/-22%, while women who had had a Pap test in 2001 were 43+/-36%. Women who reported never having had a Pap test before coming to the HIV clinic were more often from the south than the north of Italy (17.9+/-49% from the north, 18+/-53% from the center and 9.3+/-83.9% from the south; p<0.001). This a difference disappeared when comparing the women who had had a Pap test in 2001 (28+/-39.6% from the north, 31.6+/-44.2% from the center and 25.6+/-45.7% from the south; p=0.88). Despite the published guidelines in Italy, only 38% of women had ever had a Pap test before coming to the HIV clinic and only 43% had had a Pap test in 2001. Strategies aimed to improve these proportions should be rapidly implemented at all levels of care organization.

Diagnosis of HIV infection in pregnancy: data from a national cohort of pregnant women with HIV in Italy.

We analysed the characteristics of the pregnancies with a previously undetected HIV infection in a national observational study of pregnant women with HIV in Italy. In a total of 443 pregnancies with available date of HIV diagnosis, 118 were characterized by a previously undetected HIV infection (26.6%, 95% CI 22.5-30.8). The following factors were independently associated with this occurrence in a multivariate analysis (adjusted odds ratios; 95% CIs): foreign nationality (5.1, 2.8-9.3); no pre-conception counselling (35.9, 4.8-266.1); first pregnancy (2.1, 1.2-4.0); asymptomatic status (6.8, 1.5-30.6). Women with previously undetected infection started antiretroviral treatment significantly later during pregnancy (P < 0.001). Missed diagnosis was responsible for one case of transmission. A high rate of previously undetected HIV infection was observed. This suggests a good HIV detection during pregnancy, but also the need to reinforce HIV testing strategies among women of childbearing age. We identified some determinants which may be considered for intervention measures.