Minimal prevalence of HPV vaccination and common occurrence of high-risk HPV types in pregnant women with HIV: data from a national study in Italy.

Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.

CD4/CD8 ratio in pregnant women with HIV and its association with pregnancy outcome: data from a national study in Italy.

PURPOSE: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. METHODS: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. RESULTS: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111-0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082-5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690-6.900). CONCLUSION: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Pregnancy and neonatal outcomes in women with HIV-1 exposed to integrase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors: an observational study.

PURPOSE: Recommended regimens for pregnant women with HIV-1 are composed of two nucleoside reverse transcriptase inhibitors (NRTI) plus either a ritonavir-boosted protease inhibitor (PI) or an integrase strand transfer inhibitor (ISTI), with non-nucleoside reverse transcriptase inhibitors (NNRTI) representing an alternative drug class. The study's purpose was to compare these three options in terms of pregnancy outcomes. METHODS: Data from a national observational study of pregnant women with HIV-1 were used. The analysis included all pregnancies reported between 2008 and 2018, ending in live births and exposed within 32 weeks of gestation to three-drug regimens composed of a NRTI backbone plus a PI, a NNRTI or a ISTI, without class switching during pregnancy. Clinical and laboratory outcomes were evaluated in univariate and multivariable analyses. RESULTS: Overall, 794 exposed pregnancies were analyzed (PI 78.4%, NNRTI 15.4%, ISTI 6.2%). Almost all outcomes had similar rates in the three groups. Women who received PI in pregnancy were less likely to be virologically suppressed at third trimester. PI use was associated with higher bilirubin and triglyceride levels, and ISTI use with a lower rate of low birthweight. The differences in viral suppression at third trimester and in low birthweight were not maintained in multivariable analyses that were adjusted for confounders. DISCUSSION: We found no major differences in a wide range of outcomes relevant for pregnant women with HIV. Such results are reassuring, and this information may be helpful in a context of preconception counseling when therapeutic choices for pregnancy are discussed between women and care providers.

Prevalence, Correlates and Outcomes of Smoking in Pregnant Women with HIV: A National Observational Study in Italy.

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

Vaginal delivery in women with HIV in Italy: results of 5 years of implementation of the national SIGO-HIV protocol.

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.

Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study.

BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

Pregnancy outcomes in HIV-infected women of advanced maternal age.

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.

Safe conception for HIV-discordant couples: insemination with processed semen from the HIV-infected partner.

OBJECTIVE: The objective of the study was to evaluate the safety of semen washing with intrauterine insemination (SW-IUI) for achieving pregnancy when the man is human immunodeficiency virus (HIV) infected and the woman is HIV negative. STUDY DESIGN: We conducted a retrospective analysis of 635 HIV-discordant couples enrolled in a SW-IUI program and followed up 367 Italian women. We computed pregnancy, live birth, and multiple delivery rates and assessed the women's postinsemination HIV status. RESULTS: The retrospective analysis included 635 couples (2113 SW-IUI cycles): 41% of the women (95% confidence interval [CI], 37-45%) had a live birth (per-cycle live birth rate 13%; 95% CI, 11-14%). HIV status after SW-IUI was negative when available but unknown for 26% of the women: missing HIV status was not associated with correlates of HIV risk. The follow-up study included 367 couples (1365 cycles): 47% of the women (95% CI, 42-52%) had a live birth (per-cycle rate 14%; 95% CI, 12-16%). Ascertainment of postinsemination HIV status was complete and confirmed no HIV transmission attributable to SW-IUI. The upper 95% confidence limit of the HIV transmission rate was 1.8 per 1000 cycles in the retrospective analysis and 2.7 per 1000 cycles in the follow-up study. CONCLUSION: SW-IUI appears to be a safe and effective method for achieving pregnancy in HIV-discordant couples in which the man is HIV infected.

Glucose plasma levels and pregnancy outcomes in women with HIV.

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 cesarean 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.

Predictors of low ovarian reserve in cART-treated women living with HIV.

ABSTRACT: Ovarian dysfunction and lower circulating anti-Müllerian hormone (AMH) feature women living with HIV (WLWH). Because treated human immunodeficiency virus (HIV) infection is characterized by a pro-inflammatory/oxidative phenotype resulting in residual comorbidity, we sought to investigate possible associations between plasma AMH and markers of inflammation, immune activation/senescence/exhaustion, oxidative stress as well as comorbidities in a cohort of combined anti-retroviral therapy (cART)-treated WLWH versus age-matched HIV-uninfected, healthy women.Eighty WLWH on effective cART aged 25 to 50 years and 66 age-matched healthy women were enrolled. We measured: plasma AMH, IL-6, reactive oxygen species modulator 1 (ROMO1) (ELISA); plasma tumor necrosis factor α, IL-10, soluble vascular cell adhesion molecule 1, osteopontin (Luminex); CD4/CD8 activation (CD38/CD69), apoptosis (CD95), exhaustion (PD1), maturation (CD45RA/CD45R0/CD127/CCR7), recent thymic emigrants (CD31/CD103) (flow cytometry). Mann Whitney and chi-squared tests were used. Univariate and multivariate logistic regression analyses were used to assess factors associated with low AMH (≤1 ng/mL).Compared to healthy women, WLWH were more frequently non-Caucasian, drug/alcohol abusers, with history of late menarche, lower hormonal contraceptive use, with higher gravidity and lower parity. WLWH showed significantly lower AMH (P = .004) as well as higher ROMO1 (P = .0003) and tumor necrosis factor α (P < .0001). The multivariate analyses revealed ROMO1 (adjusted odds ratio [AOR]: 1.42, P = .03) and HIV infection (AOR: 8.1, P = .0001) as independently associated with low AMH. The logistic regression model with both HIV status and ROMO1 (a marker of oxidative stress) confirmed HIV as the only predictor of low AMH (AOR: 17, P = .0003).Despite effective cART, WLWH showed lower AMH compared to age-matched peers, indicating pre-mature ovarian ageing. Both HIV and oxidative stress are independently associated with low AMH, emphasizing the impact of HIV-associated oxidative stress on reproductive aging.

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

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.

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

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/mm(3)), 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.

Weight gain during pregnancy in women with HIV receiving different antiretroviral regimens.

BACKGROUND: No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. METHODS: Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. RESULTS: Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). CONCLUSIONS: No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.

BACKGROUND: There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. METHODS: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth (≥22 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. RESULTS: Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. CONCLUSIONS: Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss.

HIV RNA viral load and CD4+ T-cell counts in HIV-infected pregnant women with and without treatment discontinuation in early pregnancy.

BACKGROUND: In pregnant women taking antiretroviral treatment at conception treatment may be transiently stopped for safety concerns. Limited data are available on the consequences of such discontinuations. METHODS: We used data from a national study to compare different treatment pathways during pregnancy. Overall, 321 women were evaluated and classified into three groups: women not on treatment at conception and who started treatment during pregnancy (starters; n=91); women on treatment at conception who temporarily discontinued treatment during first trimester (discontinuers; n=114); and women on treatment at conception who maintained treatment (continuers; n=116). RESULTS: At conception, the three groups had similar CD4+ T-cell counts (499, 495 and 470 cells/mm3, respectively; P>0.10); starters had significantly higher median HIV RNA levels at conception (5,690 copies/ml) compared with both continuers (58 copies/ml, P<0.001) and discontinuers (49 copies/ml, P<0.001). Continuers maintained undetectable HIV RNA at all pregnancy trimesters, while discontinuers showed at first and second trimester transient negative effects on HIV (4,776 and 386 copies/ml, respectively) and CD4+ T-cell levels (376 and 392 cells/mm3, respectively), which were reversed at last trimester (52 copies/ml and 432 cells/mm3, respectively). No significant differences were observed among the groups in HIV RNA and CD4+ T-cell counts at third trimester, preterm delivery, low birth weight or mode of delivery. The number of cases of HIV transmission and birth defects were too limited to allow comparisons. CONCLUSIONS: Early discontinuation of antiretroviral treatment in pregnancy produces transient virological and immunological effects without precluding the achievement of a good viral suppression at the end of pregnancy; no clinical consequences were observed.

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

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.

Brief Report: Abacavir/Lamivudine and Tenofovir/Emtricitabine in Pregnant Women With HIV: Laboratory and Clinical Outcomes in an Observational National Study.

BACKGROUND: Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study. METHODS: Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC. RESULTS: The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P < 0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030). CONCLUSIONS: In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

Evolving treatment implementation among HIV-infected pregnant women and their partners: results from a national surveillance study in Italy, 2001-2015.

BACKGROUND: The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. METHODS: The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. RESULTS: The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV-negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P < 0.001), and in the proportion of HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV-negative partners. CONCLUSIONS: The results suggest good implementation of antiretroviral treatment among HIV-positive women and their HIV-positive partners, but no implementation, even in recent years, of Pre-Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.