Is "option B+" also being adopted in pregnant women in high-income countries? Temporal trends from a national study in Italy

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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

Lipodistrophy before Pregnancy Is a Protease Inhibitor-independent Predictor of Hypertriglyceridemia during Pregnancy in HIV-infected Pregnant Women

Little is known about serum lipid changes during pregnancy in HIV-infected women with a previous history of lipodistrophy (LD)

Treatment with protease inhibitors and coinfection with hepatitis C virus are independent predictors of preterm delivery in HIV-infected pregnant women.

In a recent study, Cotter et al. [1] analyzed a cohort of HIV-infected pregnant women followed at a single site, to examine the risk of preterm delivery and other pregnancy outcomes. Their results indicated that combination therapy with protease inhibitors (PIs), compared with monotherapy and combination therapy without a PI, is independently associated with preterm delivery. Such results are in accordance with those reported in a common analysis of 2 European cohorts [2], but a previous US study found no association between combination therapy and preterm delivery [3]. The role played by PIs in preterm delivery remains uncertain, because none of the studies controlled for indication for antiretroviral therapy, thereby not ruling out the possibility that treatment with PIs represents a marker for more-advanced disease [4]. We analyzed data from the largest surveillance study currently being conducted in Italy of the use of antiretroviral drugs in pregnancy [5], to establish the role played by PIs in preterm delivery after controlling for important prognostic cofactors. For the purpose of this analysis, we considered all pregnancies that resulted in the delivery of a live newborn (n=417) or in neonatal death (n=2) from all the HIV-positive women enrolled in our observational study between December 2001 (the date of the start of the study) and March 2006. Nonsingleton pregnancies and pregnancies that ended in spontaneous or voluntary abortion or in intrauterine death were excluded. Information and measurements were collected at routine visits performed during the 3 trimesters of pregnancy (with no restrictions in gestational age at entry into prenatal care). Gestational age at birth was determined on the basis of the last menstrual period, ultrasound biometry, or both. Preterm delivery was defined as delivery before 37 completed weeks of gestation. Unadjusted and adjusted odds ratios and 95% confidence intervals were used to estimate in univariate and multivariate logistic regression models the association of different variables with preterm delivery. All the analyses were performed using SPSS software (version 13.0.1; SPSS). Preterm delivery occurred in 96 (22.9%) of 419 women. Antiretroviral therapy (combination therapy in all cases) was present in 309 women at second trimester (81.1%) and in 366 women (91.3%) at third trimester. PI use occurred in 31.3% and 39.8% at second and third trimester, respectively. Sixty-five percent of the women had an indication for antiretroviral treatment for their own health. In univariate analysis, the following baseline variables were significantly associated with preterm delivery: (1) higher age at conception (P=.023); (2) hepatitis C virus (HCV) coinfection (P<.001); and (3) prior pregnancies (P=.017). No association was found for hepatitis B virus coinfection, a prior AIDS diagnosis, sexually transmitted infections, alcohol or substance abuse, and cigarette smoking (P≥.10, for all). The multivariate logistic regression models included the 3 significantly related variables (1–3) indicated above plus the following: (4) indication for antiretroviral treatment during pregnancy (maternal health or only for prophylaxis of vertical transmission); (5) prior preterm delivery; (6) treatment with PIs; (7) HIV RNA load (log10 transformed); (8) CD4 cell count; and (9) any antiretroviral treatment. The status with respect to variables 6–9 was defined separately at second and third trimester, and 2 separate logistic models were designed using the same baseline data (variables 1–5) plus data from the relevant trimester for variables 6–9. The results of the multivariate analysis are shown in table 1. Use of PI and HCV coinfection remained consistently associated with preterm delivery after age, prior pregnancies, prior preterm deliveries, any antiretroviral treatment, indication for antiretroviral treatment, HIV RNA load, and CD4 cell count were controlled for. View larger version: In this page In a new window Download as PowerPoint Slide Table 1. Association between preterm delivery and prognostic factors in a multivariate analysis. Our study provides important new information: first, we were able to confirm the effect of PIs on preterm delivery after controlling for several potential confounding variables, including indication for antiretroviral treatment. The observed rate of preterm delivery among women receiving PIs at second trimester was 32.2%, compared with 18.2% in women not receiving PIs. These figures and the observed size of the effect—a 2-fold adjusted increase in risk attributable to PI use—confirms the results reported by others. Our study, however, has the additional advantage of being entirely based on women enrolled in recent years, with combination therapy as standard treatment and a high proportion of women receiving PIs. The risk assessment, therefore, is based on current standards of care. We also describe an independent role for HCV coinfection in preterm delivery. Rates of preterm delivery in women with and without HCV coinfection were 38.6% and 17.1%, respectively, with a 2-fold increase in risk. Further studies should explore the mechanisms responsible for such an association

Antiretroviral therapy at conception in pregnant women with HIV in Italy: wide range of variability and frequent exposure to contraindicated drugs.

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 nuceloside 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), zodovudine (50.0%), stavudine (d4T; 38.0%), nevirapine (25.7%), didanosine (ddl; 17.7%) and nelfinavir (17.7%). Treatment 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 = =.033), whereas being on nevirapine was associated with a lower risk (OR: 0.58; 95% CI: =.38-0.81, P = =.013). CONCLUSIONS: Our data show that treatment at conception frequently represents the regimen previously selected for the treatment of the non-pregnant women. THe observed rates of exposure to contraindicated treatment shoud lead prescribing physicians to consider in HIV-positive women therapeutic choice that take into account the likelihood of an unplanned pregnancy. Such as approach is likely to reduce not only unintended exposures to contraindicated drugs, but also therapeutic changes during pregnancy

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 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

Plasma lipid profile in pregnant women with HIV receiving nevirapine.

Limited information is currently available on the metabolc profile of nevirapine in pregnancy. We used data from a national observational study to evaluate plasma lipid profile in pregnant women receiving nevirapine. Lipid values were collected during routine clinical visits. Midpregnancy (second trimester) lipid values were analyzed according to use of nevirapine, calculating differences and 95% confidence intervals (CI) between women taking and not taking this drug. In order to adjust for possible confounders, multivariable models were constructed using ad dependent variables levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-choleserol (LDL-C), triglyceride (TG) levels and TC/HDL-C ratio, and as independent variables age, body weight, previous treatment history, CD4 count and presence of any antiretroviral therapy, use or nonuse of protease inhibitors, stavudine, and nevirapine at the time of blood sampling. Overall, 375 women had available data for analysis. Pregnant women on nevirapine, compared to women not taking this drug, had in univariate analyses higher levels of HDL-C (difference: + 13.0mg/dL (95%CI 7.4-18.6), p<0.001), lower values of TC/HDL-C ratio (difference: 0.51 (0.23-0.80), p < 0.001) and a trend for lower levels of triglycerides (difference: 17.6mg/dl (0.7-35.9), p= 0.06). Higher HDL-C levels were also associated with use of protease inhibitors and with no previous antiretroviral experience before pregnancy. The association with higher HDL-C levels were confirmed in multivariable analysis. Our study indicates in pregnant women an association between nevirapine use and higher HDL-C levels. Further studies should assess whether this effect is due to an intrinsic activity of nevirapine and define the potential mechanisms involved