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.

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.

Plasma lipid profile in pregnant women with HIV receiving nevirapine.

Limited information is currently available on the metabolic 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 as dependent variables levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (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 associations with higher HDL-C levels were confirmed in multivariable analyses. 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.

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

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

Is the interruption of antiretroviral treatment during pregnancy an additional major risk factor for mother-to-child transmission of HIV type 1?

BACKGROUND: There is currently an experts' agreement discouraging interruption of antiretroviral treatment (ART) during the first trimester of pregnancy in women infected with human immunodeficiency virus type 1 (HIV-1). However, this recommendation is poorly supported by data. We evaluated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission. METHODS: Logistic regression models were performed in a prospective cohort of 937 children who were perinatally exposed to HIV-1 to estimate adjusted odds ratios for confounding factors on mother-to-child transmission, including maternal interruption of ART. RESULTS: Among 937 pregnant women infected with HIV-1, ART was interrupted in 81 (8.6%) in the first trimester and in 11 (1.2%) in the third trimester. In the first trimester, the median time at suspension of ART was 6 weeks (interquartile range [IQR], 5-6 weeks) and the time without treatment was 8 weeks (IQR, 7-11 weeks). In the third trimester, the median time at suspension of ART was 32 weeks (IQR, 23-36 weeks) and the time without treatment was 6 weeks (IQR, 2-9 weeks). The plasma viral load was similar in women who had treatment interrupted in the first trimester and in those who did not have treatment interrupted. Overall, the rate of mother-to-child transmission in the whole cohort was 1.3% (95% confidence interval [CI], 0.7%-2.3%), whereas it was 4.9% (95% CI, 1.9%-13.2%) when ART was interrupted in the first trimester and 18.2% (95% CI, 4.5%-72.7%) when ART was interrupted in the third trimester. In the multiple logistic regression models, only interruption of ART during either the first or the third trimester, maternal mono- or double therapy, delivery by a mode other than elective cesarean delivery, and a viral load at delivery >4.78 log(10) copies/mL were independently associated with an increased rate of mother-to-child transmission. CONCLUSIONS: Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester. This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health.

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.

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.

Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed to Mycobacterium tuberculosis: a pilot study.

RATIONALE: Existing data on the effect of treatment of latent tuberculosis infection (LTBI) on T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens are contradictory. Differences in technical aspects of the assays used to detect this response and populations studied might explain some of these discrepancies. In an attempt to find surrogate markers of the effect of LTBI treatment, it would be important to determine whether, among contacts of patients with contagious tuberculosis, therapy for LTBI could cause changes in MTB-specific immune responses to a variety of RD1-antigens. METHODS AND RESULTS: In a longitudinal study, 44 tuberculin skin test+ recent contacts were followed over a 6-month period and divided according to previous exposure to MTB and LTBI treatment. The following tests which evaluate IFN-gamma responses to RD1 antigens were performed: QuantiFERON TB Gold, RD1 intact protein- and selected peptide-based assays. Among the 24 contacts without previous exposure that completed therapy, we showed a significant decrease of IFN-gamma response in all tests employed. The response to RD1 selected peptides was found to be more markedly decreased compared to that to other RD1 antigens. Conversely, no significant changes in the response to RD1 reagents were found in 9 treated subjects with a known previous exposure to MTB and in 11 untreated controls. CONCLUSION: These data suggest that the effect of INH prophylaxis on RD1-specific T-cell responses may be different based on the population of subjects enrolled (recent infection versus re-infection) and, to a minor extent, on the reagents used.

Lipodystrophy is an independent predictor of hypertriglyceridemia during pregnancy in HIV-infected women.

Lipid values were measured during pregnancy in HIV-infected, treatment-experienced women. A previous history of lipodystrophy was associated with significantly higher triglyceride values at all pregnancy trimesters. In multivariate analyses lipodystrophy independently increased the risk of hypertriglyceridemia by threefold at the first trimester, and by eightfold at the second and third trimesters. Protease inhibitor treatment was also independently associated with hypertriglyceridemia.

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 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.

Application of a molecular panel to demonstrate enterotropic virus shedding by healthy and human immunodeficiency virus-infected patients.

We used a molecular panel, targeting seven enteric viruses, to explore the advantage of using molecular methods to establish the etiology of enteric diseases and to evaluate the prevalence of enteric viruses in asymptomatic human immunodeficiency virus-infected patients. This approach favors rapidity and sensitivity of laboratory diagnosis of viral enteric syndromes.

Primary Toxoplasma gondii infection in a pregnant human immunodeficiency virus-infected woman.

We report a 36-year-old HIV-infected woman who developed primary Toxoplasma gondii infection during pregnancy that was treated with spiramycin and antiretroviral drugs. There was no vertical transmission of toxoplasmosis and HIV.

Monophyletic HIV type 1 CRF02-AG in a nosocomial outbreak in Benghazi, Libya.

A cluster of HIV-1 infection has been identified in Libya in 1999, involving 402 children admitted to "El-Fath" Children's Hospital in Benghazi (BCH) during 1998 and 19 of their mothers. Nosocomial transmission has been indicated as responsible for the spread of infection. Out of this group, 104 children and 19 adult women have been followed at the National Institute for Infectious Diseases L. Spallanzani in Rome during 1 year. At BCH, all children had received intravenous infusions but not blood or blood products. A single child receiving a blood transfusion in 1997 and the 17 infected mothers were never hospitalized in Benghazi. In addition, two nurses were diagnosed as HIV-1 infected. In 40 subjects out of this group HIV-1 gag, env, and pol fragments were amplified and sequenced. The phylogenetic analyses showed that a monophyletic recombinant HIV-1 form CRF02-AG was infecting all of the HIV-1-seropositive patients admitted at BCH with no close similarities to the other CRF02-AG reported to GenBank. A different strain was found in the child infected by blood transfusion. The data thus suggest a highly contagious nosocomial spread of HIV-1 infection and possibly transmission of the virus from child to mother during breastfeeding in connection with primary HIV-1 infection.

A nosocomial and occupational cluster of hepatitis A virus infection in a pediatric ward.

We describe a cluster of acute hepatitis A virus (HAV) infection that involved two patients and one physician in the pediatric unit where two children with acute HAV infection had been housed. An interview with the unit personnel revealed several breaches in infection control measures and the lack of vaccination of healthcare workers against HAV .