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Purpose: To evaluate the maternal and neonatal safety of vaginal delivery in women with HIV following the implementation of a national protocol in Italy. Methods: Vaginal delivery was offered to all eligible women who presented antenatally at twelve participating clinical sites. Data collection and definition of outcomes followed the procedures of the National Program on Surveillance on Antiretroviral Treatment in Pregnancy. Pregnancy outcomes were compared according to the mode of delivery, classified as vaginal, elective cesarean (ECS) and non-elective cesarean section (NECS). Results: Among 580 women who delivered between January 2012 and September 2017, 142 (24.5%) had a vaginal delivery, 323 (55.7%) had an ECS and 115 (19.8%) had an NECS. The proportion of vaginal deliveries increased significantly over time, from 18.9% in 2012 to 35.3% in 2017 (p < 0.001). Women who delivered vaginally were younger, more commonly nulliparous, diagnosed with HIV during current pregnancy, and antiretroviral-naïve, but had a slightly longer duration of pregnancy, with significantly higher birthweight of newborns. NECS was associated with adverse pregnancy outcomes. The rate of HIV transmission was minimal (0.4%). There were no differences between vaginal and ECS about delivery complications, while NECS was more commonly associated with complications compared to ECS. Conclusions: Vaginal delivery in HIV-infected women with suppressed viral load appears to be safe for mother and children. No cases of HIV transmission were observed. Despite an ongoing significant increase, the rate of vaginal delivery remains relatively low compared to other countries, and further progress is needed to promote this mode of delivery in clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31-65 % and 2-5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy., Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis., Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22-1.71] p < 0.0001)., Conclusions: This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Neoangiogenesis is particularly abundant in small-cell lung cancer (SCLC) and is associated with poor prognosis. As a result of the promising nature of phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line chemotherapy with cisplatin-etoposide for treatment of extensive disease SCLC. We present the treatment rationale and study design of GOIRC trial (FARM6PMFJM study), a multicenter randomized phase III study, supported by AIFA (Agenzia Italiana del Farmaco)., Patients and Methods: Patients are randomized to receive either cisplatin 25 mg/m(2) and etoposide 100 mg/m(2) intravenously on days 1 to 3 (control arm) or the same chemotherapy combined with bevacizumab 7.5 mg/kg intravenously on day 1 (experimental arm). Treatment is repeated every 3 weeks and for a maximum of 6 courses. Patients randomized to the experimental arm in the absence of disease progression after 6 cycles continue bevacizumab alone until progression or for a maximum of 18 courses. Tumor assessment is done every 3 cycles. Major eligibility criteria are: age ≥ 18 years; histologically or cytologically documented extensive disease SCLC; Eastern Cooperative Oncology Group performance status ≤ 2; adequate hematological, hepatic and renal functions; no history of grade 2 or higher hemoptysis; and no evidence of tumor cavitation. The primary end point of this study is overall survival. Secondary end points include response rate, time to progression, and toxicity., Conclusion: An interim futility analysis was performed by an Independent Data Monitoring Committee in September 2013 and the trial obtained approval to continue. As of July 31, 2014, 171 patients of 206 planned have been randomized., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2013 RCOG.)

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.

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.

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.

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.

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.

Methods: Data from a large national surveillance study was used to describe antiretroviral regimens in pregnant women with HIV, with particular reference to the presence at conception of antiretroviral treatments contraindicated in pregnancy. Therapeutic changes during pregnancy were also analysed., Results: Among 334 women on antiretroviral treatment at conception, less than half (42.4%) reported current pregnancy as planned. A large number of different regimens (80) was observed. All the regimens included at least one nucleoside or nucleotide reverse transcriptase inhibitor. Non-nucleoside reverse transcriptase inhibitors and protease inhibitors were present in similar proportions (39.2% and 40.7%, respectively). The most commonly used drugs were lamivudine (83.2% of regimens), zidovudine (50.0%), stavudine (d4T; 38.0%), nevirapine (25.7%), didanosine (ddl; 17.7%) and nelfinavir (17.7%). Treament with efavirenz (13.5% of regimens) and ddl+d4T (9.6%) was markedly frequent. Use of efavirenz at conception was associated with a subsequent treatment change during pregnancy (odds ratio [OR]: 13.2.; 95% confidence interval [CI]: 3.2-53.8, P < 0.001). A similar but less strong association was found for ddl (OR: 1.8; 95% CI: 1.03-3.25, P = 0.033), whereas being on nevirapine was associated with a lower risk (OR: 0.58; 95% CI: 0.38-0.81, P = 0.013)., Conclusions: Our data show that treatment at conception frequently represents the regimen previously selected for the treatment of the non-pregnant woman. The observed rates of exposure to contraindicated treatment should lead prescribing physicians to consider in HIV-positive women therapeutic choices that take into account the likelihood of an unplanned pregnancy. Such an approach is likely to reduce not only unintended exposures to contraindicated drugs, but also therapeutic changes during pregnancy.

Objective: The assessment of the association of cervicovaginal infections during pregnancy with preterm (pPROM) and term (PROM) premature rupture of membranes, preterm delivery, mid-trimester miscarriage and intrauterine death, and the definition of the risk factors that identify pregnant women who should have a cervicovaginal culture., Methods: We retrospectively studied the relationship between pregnancy outcomes and cervicovaginal infections in 3217 pregnant women between January 1998 and December 1999. Microbiological assessment included Gram staining and specific cultures; bacterial vaginosis was diagnosed by Amsel's criteria. We also studied the medical, obstetric, sexual, demographic and social history of 11,212 pregnant women who underwent cervicovaginal culture between January 1992 and December 2001., Results: Overall, 1425 of the 3217 cultures (44.3%) were positive. The micro-organisms most frequently found were: yeasts (44%), Ureaplasma urealiticum (29%); group B streptococcus (15%); and bacterial vaginosis (11%). Cervicovaginal cultures were found positive in 84.6% of pPROM, 55.0% of PROM, 50.8% of preterm deliveries, 43.8% of mid-trimester miscarriages, 31.4% of intrauterine deaths and in 33.5% of controls. Among the 11 212 cervicovaginal cultures considered in the second study, an overall 6301 (56.2%) were positive, 2711 (43%) in asymptomatic women. Cervicovaginal infections were associated with country of origin, age under 25 years, age at first intercourse under 15 years, more than ten partners, more than one partner in the past 6 months, prior abortions, past sexually transmitted diseases (STDs) and HIV infection., Conclusion: Cervicovaginal infections were significantly associated with PROM (p<0.0001), pPROM (p<0.0001) and preterm delivery (p<0.0001), but not with intrauterine death. The association with mid-trimester miscarriage approached statistical significance (p=0.06). The main risk factors for cervicovaginal infections were country of origin, age under 25 years, age at first intercourse under 15 years, more than ten partners, more than one partner in the past 6 months, prior abortions, past STDs and HIV infection.