Strategies for Prevention of Mother-to-Child Transmission Adopted in the "Real-World" Setting: Data From the Italian Register for HIV-1 Infection in Children.

BACKGROUND: Strategies for prevention of HIV-1 mother-to-child transmission (PMTCT) have been continuously optimized. However, cases of vertical transmission continue to occur in high-income countries. OBJECTIVES: To investigate changes in PMTCT strategies adopted by Italian clinicians over time and to evaluate risk factors for transmission. METHODS: Data from mother-child pairs prospectively collected by the Italian Register, born in Italy in 1996-2016, were analyzed. Risk factors for MTCT were explored by logistic regression analyses. RESULTS: Six thousand five hundred three children (348 infections) were included. In our cohort, the proportion of children born to foreign mothers increased from 18.3% (563/3078) in 1996%-2003% to 66.2% (559/857) in 2011-2016 (P < 0.0001). Combination neonatal prophylaxis use significantly (P < 0.0001) increased over time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in early preterm infants. The proportion of vaginal deliveries in women with undetectable viral load (VL) increased over time and was 9.9% (85/857) in 2011-2016; no infection occurred among them. In children followed up since birth MTCT, rate was 3.5% (96/2783) in 1996-2003; 1.4% (36/2480) in 2004-2010; and 1.1% (9/835) in 2011-2016. At a multivariate analysis, factors associated with MTCT were vaginal delivery with detectable or missing VL or nonelective caesarean delivery, prematurity, breastfeeding, lack of maternal or neonatal antiretroviral therapy, detectable maternal VL, and age at first observation. Previously described increased risk of offspring of immigrant women was not confirmed. CONCLUSIONS: Risk of MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large combination neonatal prophylaxis use in preterm infants was observed, even if data on safety and efficacy in prematures are poor.

Kinetic of Virologic Response to Pegylated Interferon and Ribavirin in Children With Chronic Hepatitis C Predicts the Effect of Treatment.

BACKGROUND: Chronic hepatitis C is a global health problem. Although new, highly effective and safe direct-acting antivirals have been approved for adults, the only drugs currently registered for children are pegylated interferon and ribavirin. The timelines for the pediatric approval of the new treatment regimens are far off. Three phase II-III pediatric trials with direct-acting antivirals are recruiting, and the estimated dates of completion of these studies range between April 2018 and January 2023. METHODS: The aim of this study was to evaluate the value of on-treatment virologic response (VR) as predictor of sustained virologic response (SVR) in a cohort of Italian children with chronic hepatitis C and to establish possible stopping rules. RESULTS: Sixty-four children were enrolled (January 2012 to December 2015). SVR rate was 79.7% (51/64). VR at weeks 2 to 12 were shown to be robust predictors for the attainment of SVR. The positive predictive values of VR at weeks 8 and 12 were 98% and 92.7%, respectively. The negative predictive values at the same treatment weeks were 92.9% and 100%, indicating that no child who did not achieve VR at week 12 obtained SVR and that the likelihood of achieving SVR if still positive at week 8 was very low. CONCLUSIONS: Our results suggest for the first time that VR at week 8 could be considered a reliable predictor of SVR. Monitoring viral kinetics is useful for predicting the success of pegylated interferon and ribavirin therapy in children.

Bone disorders in children and adolescents with chronic HCV infection.

BACKGROUND AND AIMS: Although several studies have demonstrated a higher incidence of bone disorders in HCV-infected adults, the bone turnover alterations occurring in children and adolescents with chronic hepatitis C has not been thoroughly focused yet. We performed a study on a cohort of 30 HCV infected caucasian children and adolescents to assess the prevalence of osteodystrophy and evaluate a possible prophylactic and therapeutic approach. METHODS: Data regarding biochemical markers of bone metabolism were collected. Moreover, results of ultra-sonographic bone densitometry yearly performed were evaluated in comparison with data obtained from more than 500 healthy children and adolescents. RESULTS: Osteocalcin and telopeptide of the collagen molecule type-1, CTX, appeared higher than normal in 8/30 and in 7/30 cases respectively; the 25OH vitamin D values were normal in 25/28 cases. By densitometry osteoporosis was detected in 2 patients and osteopenia in other 5. After stratification of cases by age groups, the incidence of osteopenia/osteoporosis appeared higher among children than among adolescents. Osteocalcin levels tended to be higher in cases where hepatic fibrosis were not detected. CONCLUSIONS: The higher number of cases of osteopenia/osteoporosis in children than in adolescents is worthy of note, although not statistically significant. Ultrasound densitometry confirmed its important early diagnostic role in asymptomatic HCV infected children; moreover, also the increase in serum levels of osteocalcin may be considered as early marker of osteodystrophy of complementary value. Larger studies will be needed to confirm the efficacy and safety of antiviral and supportive care in these patients.

Genotypic determination of HIV tropism in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy.

The aim of this study was to determine the coreceptor tropism by performing genotypic HIV-1 tropism testing in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy. Genotypic coreceptor tropism was determined in patients with HIV-1 RNA<100 copies/mL using PBMC samples by gp120 V3 sequencing followed by geno2pheno interpretation (set at a false positive rate [FPR] of 20%) and in patients with ≯100 copies/mL using plasma samples (set at a FPR of 20%), according to European guidelines. Out of 55 patients, 50 had an HIV-1 subtype B strain, and mean (SD) age was 18.2 (4.6) years. The median duration of antiretroviral therapy was 13 years (range, 3-23). Thirty-three (60%) patients harbored the R5 virus. At the time of the testing, the median CD4+ T lymphocyte cell count and percentage were 705 cells/mm3 (474-905) and 32.5% in group R5 and 626 cells/mm3 (450-755) and 31.7% in group X4/D-M, respectively. The nadir of CD4+ T-cell count in groups R5 and X4/D-M were 322 cells/mm3 (230-427) and 340 cells/mm3 (242-356), respectively. These differences were not statistically significant. Fifteen patients had HIV-1 RNA ≯50 copies/mL. The median HIV-1 RNA and HIV-1 DNA were comparable in both groups without a statistical difference. The study provides an overview of the prevalence of coreceptor tropism in a cohort of patients who were vertically infected with HIV-1. The high prevalence of X4/D-M-tropic strains may simply reflect the long-term exposure to HIV.

Revision of 120 tibial infected non-unions with bone and soft tissue loss treated with epidermato-fascial osteoplasty according to Umiarov.

Treatment of tibial infected non-unions with bone and soft tissue loss has to solve three problems: infection, lack of bone continuity and lack of skin coverage. The aims of treatment are infection healing, bone consolidation with preservation of limb length and soft tissue reconstruction. The most important stage in the planning is an accurate débridement. Soft tissue reconstruction can be achieved using plastic surgery, and bone reconstruction is accomplished with bone grafts or induced membrane technique, but these methods may present disadvantages and risks. Epidermato-fascial osteoplasty is a modified procedure of compression-distraction osteosynthesis that was first described by Umiarov in 1982. This procedure offers the advantages of exactly classifying the phases of simultaneous bone and soft tissue regeneration, and of eliminating large tissue losses without previous closure of soft tissues or use of grafts, because the transported fragment takes fascia and skin along during the transport and closes the edges of the soft tissue gap until the epidermic and fascial reconstruction is complete. A total of 120 patients underwent this kind of surgery between 1986 and 2010 and were followed up for 2-26 years. Average age was 34 years (range 21-57 years). Cultures were positive for Staphylococcus in all cases, and for Pseudomonas in 27 cases. Adequate antibiotic therapy was administered in collaboration with the Infectious Diseases Specialist. Tibial bone resection was from 6 to 18cm (average 9.5cm). The Ilizarov apparatus was used with the oblique wire technique for bone transport in all patients. No intraoperative complications were observed. One patient died 40 days after the operation because of pulmonary embolism. The duration of treatment for the remaining 119 patients was 7-18 months. In all cases, infection eradication, healing of regenerate bone, consolidation at the docking site (with the aid of an autoplastic bone graft in only 11 patients), and epidermic and fascial reconstruction were observed, and functional results were very good. These techniques are particularly demanding for the patient and for the surgical team, but our results demonstrate that they can provide excellent outcomes in the management of difficult cases of infected non-unions.

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.

Grade 3 anal intraepithelial neoplasia in an HIV-infected African girl.

Women with HIV infection are at increased risk of anogenital dysplasia and cancer, related to human papillomavirus infection. These neoplasms are rare in perinatally HIV-infected girls before onset of sexual activity. We report a case of high-grade anal dysplasia in a 10-year-old African girl with untreated perinatal HIV infection.

Antiretroviral use in Italian children with perinatal HIV infection over a 14-year period.

BACKGROUND: Information on the use of new antiretroviral drugs in children in the real setting of clinical fields is largely unknown. METHODS: Data from 2554 combined antiretroviral therapy (cART) regimens administered to 911 children enrolled in the Italian Register for HIV infection in children, between 1996 and 2009, were analysed. Factors potentially associated with undetectable viral load and immunological response to cART were explored by Cox regression analysis. RESULTS: Proportion of protease inhibitor (PI)-based regimens significantly decreased from 88.0% to 51.2% and 54.9%, while proportion on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens increased from 4.5% to 38.8% and 40.2% in 1996-1999, 2000-2004 and 2005-2009, respectively (p < 0.0001). Significant change in the use of each antiretroviral drug occurred over the time periods (p < 0.0001). Factors independently associated with virological and immunological success were as follows: later calendar periods, younger age at regimen (only for virological success) and higher CD4(+) T-lymphocyte percentage at baseline. Use of unboosted PI was associated with lower adjusted hazard ratio (aHR) of virological or immunological success with respect to NNRTI- and boosted PI-based regimens, with no difference among these two latter types. CONCLUSION: Use of new generation antiretroviral drugs in Italian HIV-infected children is increasing. No different viro-immunological outcomes between NNRTI- and boosted PI-based cART were observed.

HIV shedding in cervico-vaginal secretions in pregnant women.

OBJECTIVE: The purpose of this study was to evaluate the presence of HIV-1 in cervico-vaginal secretions of pregnant as compared to non-pregnant HIV-seropositive women. PATIENTS AND METHODS: We compared 43 known HIV seropositive pregnant patients versus 241 age-matched (± 2 years) control non-pregnant HIV-seropositive subjects. In pregnant patients blood and cervico-vaginal samples were obtained during each trimester of pregnancy. In control subjects the same samples were obtained at enrolment. HIV-1 RNA was measured in plasma; proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA in cervico-vaginal secretion by competitive polymerase chain reaction (cRT-PCR) and reverse transcriptase PCR. RESULTS: The genital shedding of HIV-DNA (22/43 as compared to 79/241, p = 0.02), and cell-free HIV-RNA detection (26/43 as compared to 72/241, p < .001) was more common in first-trimester pregnant than in non pregnant women. Pregnancy correlated with a significant positive trend in the cervico-vaginal load of HIV-DNA (Spearman Rho= 0.149, p= 0.012), and cell-free HIV-RNA (Spearman Rho= 0.253, p < .001), but not of HIV-RNA transcripts (Spearman Rho = 0.06, p= 0.31). After correction for potential confounders, first trimester pregnant women had increased rates of genital HIV- DNA (odds ratio = 1.94, 95% confidence interval = 1.01 3.78) and cell-free HIV-RNA (odds ratio = 4.07, 95% confidence interval = 1.97 8.41) detection compared to nonpregnant controls. CONCLUSION: The shedding of genital HIV was increased in pregnant compared to non pregnant subjects, even in patients with undetectable viremia. In this low-risk HIV-positive population the risks of vertical or horizontal transmissions should not be underestimated.

Pregnancy outcomes in women with advanced HIV infection in Italy.

Pregnancy has been associated with a low risk of HIV disease progression. Most pregnancies with HIV currently involve women who have not experienced AIDS-defining events, and are clinically classified as Centers for Disease Control and Prevention (CDC) groups A or B. We evaluated the main maternal outcomes among pregnant women with more advanced HIV disease, defined by CDC-C disease stage. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. A total of 566 HIV-infected mothers, 515 in stage A or B (CDC-AB group) and 51 in stage C (CDC-C group) were evaluated. The two groups had similar baseline characteristics. No differences were found in the main maternal and neonatal outcomes. Most of the women achieved viral suppression at end of pregnancy (>1000 copies per milliliter: CDC-C: 17.2%; CDC-AB: 13.7%). One year after delivery, HIV replication (HIV-RNA >1000 copies per milliliter) was present in 11.5% of CDC-AB women and 30.0% CDC-C women. Despite lower initial CD4 counts (300 versus 481 cells per microliter), CDC-C women maintained stable CD4 levels during pregnancy, and 1 year after delivery, a significant increase in CD4 count from preconception values was observed in both groups (CDC-C: +72 cells per microliter, p=0.031; CDC-AB: +43 cells per microliter, p<0.001). Only one AIDS event occurred in a woman with a previous diagnosis of AIDS. In CDC-C women, pregnancy is not associated with an increased rate of adverse maternal or neonatal outcomes, and a good immunovirologic response can be expected. During postpartum care, women with more advanced HIV infection should receive particular care to prevent loss of virologic suppression.

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.

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.

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.

Churg-Strauss syndrome: a diagnosis not to be forgotten.

Churg-Strauss syndrome (CSS) is a peculiar form of vasculitis with involvement of small- and medium-size arteries, histologically characterized by necrotizing granulomas in vessel walls and in perivascular tissues. The Authors report a case of CSS occurred in a young man being treated with corticosteroids for a diagnosis of asthma. The patient was hospitalized because of fever, diarrhoea and abdominal pain; the first assessment showed leucocytosis and eosinophilia,increase in flogosis indexes and anti-pANCA antibodies positive. A few days later an acute peritonitis with multiple intestinal perforations occurred and a partial resection of small bowel was performed,followed by another resection of an ileal segment because of a new double perforation close to the previous intestinal anastomosis. In the bowel resection pieces necrotizing vasculitis and granulomatous infiltrates involving lymphocytes and eosino- phils were observed. Although the severe intestinal involvement and especially the symptoms necessitating iterative surgery were significant factors of poor prognosis the patient was successfully treated firstly with metylprednisolone only and then with monthly administration of immunosuppressive drugs combined with lower daily dose of steroids. The CSS diagnosis is not to be forgotten althoughits early clinical features can be frequently mistaken for an allergic disease; an early diagnosis can allow to perform the best treatment, to reach the disease remission and to improve the quality of life of the patients.

Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease.

BACKGROUND & AIMS: The natural course of chronic hepatitis C (CHC) in children is not well understood. The aim of this study was to assess the long-term course of CHC in a large sample of otherwise healthy children. METHODS: From 1990 to 2005, 504 consecutive antihepatitis C virus (HCV)-positive children were enrolled at 12 centers of a national observatory and were followed up retrospectively/prospectively. RESULTS: Putative exposure was perinatal in 283 (56.2%) cases, parenteral in 158 (31.3%), and unknown in 63 (12.5%). At baseline, 477 (94.6%) cases were HCV RNA seropositive, 118 (24.7%) of which were treated with standard interferon alpha. Ten years after putative exposure, the outcome in 359 HCV RNA-positive, untreated patients was (1) undetectable viremia in 27 (7.5%) (by Cox regression analysis, spontaneous viral clearance was independently predicted by genotype 3 [hazard ratio 6.44; 95% confidence interval: 2.7-15.5]) and (2) persistent viremia in 332 (92%) cases. Six of these 332 cases (1.8%) progressed to decompensated cirrhosis (mean age, 9.6 years). This latter group included 5 Italian children perinatally infected with genotype 1a (4 of the mothers were drug users). Thirty-three (27.9%) treated patients achieved a sustained virologic response. CONCLUSIONS: Over the course of a decade, few children with chronic HCV infection cleared viremia spontaneously, and those who did were more likely to have genotype 3. Persistent viral replication led to end-stage liver disease in a small subgroup characterized by perinatal exposure, maternal drug use, and infection with HCV genotype 1a. Children with such features should be considered for early treatment.

Changes in circulation of B and non-B HIV strains: spotlight on a reference centre for infectious diseases in Northern Italy.

Stored demographic data and HIV RT and protease sequences of 877 HIV patients attending for the first time the HIV/AIDS outpatient clinics of a reference Infectious Diseases centre in Northern Italy between 1999 and 2006 were stratified by 3-year spanning periods according to date of HIV infection. In the period 1980--1982, new infections were entirely caused by HIV-1 subtype B strains and were all diagnosed in injection drug users, 88.9% of whom were males. Injection drug users accounted for 12.8% of new infections in 2004--2006. The frequency of heterosexually-transmitted infections consistently increased until 2000 (from almost none to 51.5%) remaining stable afterwards. About half of heterosexual patients were females. HIV infections among homosexual men increased from 0% in 1980--1982 to 15-21% between 1998 and 2006. Overall, the frequency of non-B subtypes HIV strains increased from 0% in 1980--1982 to 20.3% in 2004--2006 with a greater impact in heterosexuals (from 0% in 1980--1982 to 30.5% in 2004--2006). In conclusion, a picture of the changing scenario of circulating HIV types and subtypes in a reference Infectious Diseases centre in Northern Italy over the past 26 years is provided. A progressive modification in risk factors for HIV infection and a significant increase in the frequency of non-B HIV strains were observed.

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

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.

Endocrine pancreatic dysfunction in HIV-infected children: association with growth alterations.

BACKGROUND: The pancreatic endocrine system normally guarantees a quick and efficient response to daily metabolic perturbations, but associated data for human immunodeficiency virus (HIV)-infected patients are lacking. A prospective study was performed to evaluate pancreatic endocrine secretion and its possible association with failure to thrive among HIV-infected children. METHODS: Fourteen well-nourished, prepubertal, HIV-infected children (6 boys and 8 girls; age range, 5-11 years), none of whom were receiving protease inhibitors, and 16 clinically healthy sex- and age-matched children formed the patient group and the control group, respectively. At yearly follow-up examinations, insulin, glucagon, C-peptide, and glucose levels were measured; the ratio of insulin to glucose, the ratio of insulin to glucagon, and the homeostasis model assessment (HOMA) index were calculated; the glucagon test was administered; and growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, cortisol, and lipid patterns were evaluated. RESULTS: Insulin, glucagon, C-peptide, glucose, and HOMA measurements were significantly higher among patients, compared with control subjects, at all 3 follow-ups performed to date. The glucagon test revealed a normal glycemic response in all the healthy control subjects and a significantly impaired response in 11 patients. A significant correlation emerged between the ratio of insulin to glucagon and the growth velocity of HIV-infected children. CONCLUSION: To our knowledge, the present study provides the first evidence of altered pancreatic endocrine secretion and its association with growth failure among HIV-infected children.