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Biomedical subjects

Alessandra Viganò

Publications and source records attributed to Alessandra Viganò.

16 recordsLinked to original sources
PubMed2007

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, Highly Active↗
PubMed2006

Lopinavir/ritonavir exposure in treatment-naive HIV-infected children following twice or once daily administration.

OBJECTIVES: Lopinavir/ritonavir is approved for treatment of HIV-infected children at a dosage regimen of 230/57.5 mg/m(2) twice daily. However, once daily administration could increase convenience and patient adherence. Our study aimed at evaluating whether inhibitory concentrations are maintained in plasma following administration of lopinavir/ritonavir once daily. PATIENTS AND METHODS: Lopinavir/ritonavir was administered at the standard twice daily regimen to 21 HIV-infected children, as a component of their antiretroviral treatment. Following at least 1 month of administration, seven patients received a dose of 460/115 mg/m(2) once daily for three consecutive days. After the third dose of once daily administration, blood samples were drawn at the following times: 0 (pre-dose), 1, 2 and 4 h following administration. The pre-dose (C(min)) and the peak (C(max)) concentrations were compared with the values obtained following twice daily administration in all the study patients. RESULTS: Median (interquartile range) C(min) with the once daily regimen was 1.59 (0.77-6.85) mg/L versus 7.90 (5.45-9.77) mg/L with the twice daily regimen (P < 0.05). C(min) was considered inhibitory for wild-type virus (>1.0 mg/L) in four out of seven patients. C(max) did not differ significantly between the once daily and twice daily regimens. CONCLUSIONS: Our small pilot study suggests that lopinavir/ritonavir once daily may be a suitable regimen for antiretroviral-naive children. However, due to the high interindividual variability and low concentrations in some patients, therapeutic drug monitoring may be necessary to ensure that concentrations are adequate to inhibit viral replication. A formal clinical study of lopinavir/ritonavir once daily in treatment-naive children is warranted.

Adolescent↗
PubMed2006

Failure to eradicate HIV despite fully successful HAART initiated in the first days of life.

Highly active antiretroviral therapy (HAART) started shortly after birth resulted in reversion of human immunodeficiency virus (HIV) plasma viremia, proviral DNA in PBMC, viral culture, and serum HIV antibodies to negative. Discontinuation of HAART 2 years after apparent HIV eradication, however, was followed by virus replication, CD4 decline, and destruction of HIV-specific lymphocytes, epitomizing the impossibility of HIV eradication.

Antiretroviral Therapy, Highly Active↗
PubMed2005

A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV-infected children.

BACKGROUND: Short-term use of tenofovir (TDF) has been associated with bone mineral loss in adults and children. OBJECTIVE: To assess whether the substitution of stavudine with TDF would result in decreased bone mineral content (BMC) and bone mineral density (BMD) accrual in HIV-infected children. METHODS: The lumbar spine and whole-body BMC and BMD were measured by dual-energy x-ray absorptiometry in 16 HIV-infected children (age range: 6.4-17.9 years) on stable highly active antiretroviral therapy. Bone measurements were obtained 12 months before the switch, at baseline, and 12 months after switching to TDF. Expected changes in bone measurements were calculated from cross-sectional data obtained from 166 healthy children. RESULTS: The BMC and BMD increments observed before switching therapy did not differ from expected increments. Similarly, the changes detected during treatment with TDF did not differ significantly from those calculated in healthy controls. CONCLUSIONS: Substitution to a TDF-containing antiretroviral regimen does not seem to impair bone mineral accrual in children showing a good immunologic response to antiretroviral treatment.

Absorptiometry, Photon↗
PubMed2005

Effects of recombinant growth hormone on visceral fat accumulation: pilot study in human immunodeficiency virus-infected adolescents.

CONTEXT: Recombinant human GH (rhGH) reduces excess accumulation of intraabdominal adipose tissue (IAT) in lipodystrophic HIV-infected adults, whereas data in pediatric patients are lacking. OBJECTIVE: The objective of this study was to assess the efficacy of rhGH treatment on lipodystrophy in HIV-infected adolescents. DESIGN: The study is a prospective, 24-wk open-label study of rhGH. SETTING: The study was conducted at a referral center for pediatric HIV infection. PATIENTS AND OTHER PARTICIPANTS: Eight HIV-infected adolescents (ages, 13.7-18.5 yr), with abnormal IAT accumulation (>41 cm(2) at L4-magnetic resonance imaging) and 97 healthy controls (HC) (ages, 9.5-19.9 yr) were enrolled. INTERVENTION: rhGH was given by sc injection at a daily dose of 0.028 mg/kg. MAIN OUTCOME MEASURES: The main outcome was change in IAT at L4-magnetic resonance imaging. Body composition by dual-energy x-ray absorptiometry, glucose and lipid metabolism, and IGF-I changes were also evaluated. RESULTS: All patients completed the study period; none of them showed adverse event, and no change in the daily dose of rhGH was required. The treatment was associated with a mean height increase of 2.4 cm. From baseline to wk 24, IAT area decreased significantly by a median of 34.5% (-19.2 to -70%). Fat mass decreased significantly in patients, compared with HC, with a median loss of total, trunk, and arm and leg fat mass of 10.4, 10.9, 12.7, and 5.4%, respectively. Total, arm, and leg lean masses increased significantly, compared with HC. IGF-I increased significantly, but supraphysiological values of mild degree (2-23% over the upper normal limit) were detected in only nine of 24 samples. No significant effects on glucose metabolism, triglyceride, and cholesterol levels were observed. CONCLUSIONS: Our data showed that rhGH 0.028 mg/kg daily for 24 wk in HIV-infected adolescents reduces IAT, trunk, and also limb fat and increases lean mass. Overall, short-term rhGH is well tolerated and is not associated with a worsening of glucose and lipid metabolism.

Adipose Tissue↗
PubMed2005

Efficacy and tolerability of multiple drug therapy in HIV-infected children.

OBJECTIVES: To characterize the efficacy and tolerability of multiple drug therapy (MDT) among heavily pre-treated HIV-infected children. METHODS: An observational study of seven children treated with 4-7 antiretroviral agents. MDT regimens were chosen with regard to past antiretroviral exposure and genotypic resistance data. Five children received MDT once, one child twice and one child four times. All patients had AIDS and severe CD4+ depletion and failed >2 PI-based HAART regimens. RESULTS: Virologic response, defined as a > or =log10 decrease in plasma HIV-1 RNA at week 24, was achieved in 7/11 MDT. Successful MDT kept a sustained viral suppression (<50 copies/ml) at longest follow-up (72-96 weeks). Successful MDT obtained a great immune recovery: the median rise in absolute and percentage of CD4+ cells was 261 and 4 at week 24 and it reached 480 and 16 at 72-96 weeks. Adverse events were common but generally manageable. Mild/moderate gastrointestinal complaints and laboratory abnormalities were detected in 5/11 and 8/11 MDT. Grade 2 severity pancreatitis occurred in one case with chronic active hepatitis C. Pancreatitis resolved within 30 days of MDT interruption. CONCLUSIONS: MDT may be a therapeutic option in children who failed to respond to most standard HAART regimens.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIV-infected children.

OBJECTIVE: To assess the impact on immunological, virological and metabolic parameters of replacing protease inhibitors (PIs) with efavirenz and replacing stavudine with tenofovir in HIV-infected children. METHODS: A 48-week prospective evaluation of 28 HIV-infected children, with stable undetectable HIV-1 loads, who were taking highly active antiretroviral therapy (HAART) containing lamivudine, stavudine and a PI. Individuals were randomized to switch PI to efavirenz and stavudine to tenofovir at baseline (Group 1) or at week 24 (Group 2). Patient assessment included: clinical evaluation, viral load, CD4+ T-cell count, fasting blood levels and urine samples. RESULTS: All individuals maintained HIV RNA <50 copies/ml and unchanged CD4+ T-cell count through week 48. In Group 1 individuals, a significant decrease in cholesterol (P < 0.05), cholesterol:high-density lipoprotein (HDL) ratio (P < 0.01) and triglycerides (P < 0.05) was observed 24 and 48 weeks after the switch of HAART. The percentage of Group 1 children with increased cholesterol and triglycerides markedly decreased over the study period (from 43% to 0% and from 36% to 7%, respectively). In Group 2 individuals, unchanged lipids in the 24 weeks prior to the switch of HAART and a significant improvement on cholesterol (P < 0.05), cholesterol:HDL ratio (P < 0.01) and triglycerides (P < 0.05) were observed 24 weeks after the switch of HAART. The percentage of Group 2 children with increased cholesterol and triglycerides markedly decreased 24 weeks after the switch of HAART (from 46% to 7% and from 54% to 0%, respectively). Proteinuria and glucosuria were not detected in any individual. The mean values of serum creatinine, serum phosphorus, serum bicarbonate, estimated glomerular filtration rate, urinary microalbumin/creatinine, alpha-1-microglobulin/creatinine ratio and maximal tubular phosphate reabsorption remained unchanged in both groups. CONCLUSIONS: In HIV-infected children, switching PI to efavirenz and stavudine to tenofovir is virologically and immunologically safe, is not associated with renal impairment and provides a significant improvement in lipid profile.

Adenine↗
PubMed2004

Thyroid dysfunction in antiretroviral treated children.

BACKGROUND: A high rate of thyroid disorders has been described in HIV-infected adults treated with highly active antiretroviral therapy (HAART), but data on children are lacking. We aimed to assess thyroid function in pediatric patients. METHODS: Fifty-two HIV-infected children receiving HAART were assessed for signs of thyroid dysfunction and serum concentrations of thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroglobulin (TG), reverse triiodothyronine (rT3), anti-TG and antimicrosomal (anti-TSM) antibodies. RESULTS: Eighteen (35%) children showed thyroid abnormalities: isolated low FT4 value in 16; subclinical hypothyroidism in 1; and symptomatic hypothyroidism in 1. Children with low FT4 values as compared with the 34 children without thyroid dysfunction were similar for stage of disease, number of patients with undetectable HIV-RNA, FT3, TSH, TG, rT3, anti-TSM and anti-TG values, whereas they had shorter duration of HAART exposure (P = 0.019) and lower CD4 cell percentage (P = 0.035). The thyrotropin-releasing hormone (TRH) test was normal in all children with low FT4 values. Among children with low FT4, FT4 concentrations correlated positively with CD4 cell percentage (P < 0.05) and duration of HAART exposure (P < 0.05). The case with subclinical hypothyroidism had high basal TSH (7.3 microunits/ml), normal TSH response to TRH test and normal FT4, FT3, TG, rT3, anti-TG and anti-TSM antibodies. The case with symptomatic hypothyroidism had low FT4 (6.6 pg/ml) and high TSH (44 microunits/ml), TG (55 ng/ml), anti-TG (666 IU/ml) and anti-TSM (123 IU/ml). CONCLUSION: Thyroid abnormalities occur frequently in HAART-treated children even in the absence of clinical symptoms. These data suggest a need of regular thyroid function monitoring.

Adolescent↗
PubMed2004

Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children.

Highly active antiretroviral therapy (HAART) may be a contributory factor for a decreased bone mass and altered bone metabolism in HIV-infected children. However, the evolution of bone mineral density (BMD) and bone metabolism during HAART has not been studied yet. In the current longitudinal study we monitored the changes of BMD and bone metabolism over a period of 12 months. Thirty-two HIV-infected children (15 girls and 17 boys), aged from 6.3 to 17.7 yr, with a long duration of HAART exposure (40.0 months at baseline) were enrolled in the study. As a control group, 381 healthy volunteers of comparable age were assessed. BMD was measured at the lumbar spine and whole skeleton by dual-energy x-ray absorptiometry. Bone-specific alkaline phosphatase (BALP, as bone formation index) and N-terminal telopeptide of type I collagen (as bone resorption index) were measured in serum and urine, respectively. BMD values at baseline were significantly lower at all skeletal sites than those of control subjects. The annual increment of spine BMD was comparable to normal, whereas that of the whole skeleton was significantly lower (P < 0.04). BALP and N-terminal telopeptide of type I collagen concentrations were significantly higher compared with controls at baseline and at follow-up. BALP annual changes of HIV patients were significantly different from normal. Our data confirm the presence of low BMD and bone metabolism derangement in HIV-infected children treated with HAART. The role of possible therapeutic approach to restore bone mass and metabolism should be assessed in pediatrics.

Absorptiometry, Photon↗
PubMed2004

Adverse effects of antiretroviral therapy: focus on bone density.

Osteopenia and osteoporosis are the most important bone disorders affecting patients with HIV infection. The available data indicate that HIV-infected patients have a high prevalence of low bone mineral density. Reduced bone mass and alterations of bone metabolism have been found in HIV-infected children, adolescents and adults. The variety and complexity of changes in bone metabolism in patients with HIV infection and the different possible mechanisms triggering bone mineral loss, as well as the different stages of disease and cumulative exposure to antiretroviral drugs at the time of clinical evaluation, may contribute to the wide range of mineral loss observed and to the uncertainty of the role of specific antiretroviral medications.

Anti-Retroviral Agents↗
PubMed2003

Impaired growth hormone secretion correlates with visceral adiposity in highly active antiretroviral treated HIV-infected adolescents.

BACKGROUND: HIV-infected adults with lipodystrophy, characterized by excess accumulation of intra-abdominal adipose tissue (IAT), showed impaired growth hormone (GH) secretion. Data are lacking in paediatric lipodystrophy with the same features. METHODS: Twenty-five pubertal HIV-infected children were assessed for GH response (GH-AUC(0-120 min)) to arginine + GHRH testing, insulin-like growth factor-1 (IGF-1), IGF binding protein 3 (IGFBP-3), insulin, glucose, cholesterol, triglycerides, free fatty acids and nitric oxide levels. Body composition and IAT content were evaluated by dual-energy x-ray-absorptiometry and magnetic resonance imaging. An excess accumulation of IAT was defined as a value > 41 cm2. Differences between children with (V+) and without (V-) excess IAT were assessed by non-parametric tests and multivariate analysis. RESULTS Ten V+ (mean IAT, 82.5 cm2) and 15 V- (mean IAT, 26.8 cm2) were identified; they were similar for age (13.8 versus 14.8 years), body mass index (20.2 versus 19.5 kg/m2), male : female ratio (3/7 versus 8/7), months on highly active antiretroviral therapy (54.5 versus 55 months). V+ showed lower GH-AUC(0-120 min) (16.4 versus 31.6 microg x h/l; P = 0.002), lower IGF-1 concentrations (384 versus 515 ng/ml; P = 0.03) and higher insulin levels (17.8 versus 10.5 microIU/ml; P = 0.01) than V-. V+, as compared to V-, showed lower lean mass (total, P = 0.025; arms, P = 0.024; legs, P = 0.008) and higher fat mass (total, P = 0.0038; arms, P = 0.028; trunk, P < 0.0001). Lipid profile and glucose, IGFBP-3, nitric oxide and free fatty acids levels were similar in the two groups. GH-AUC(0-120 min) correlated negatively with IAT content and insulin levels. CONCLUSION: Impaired GH secretion is detectable in pubertal children with increased visceral adiposity and hyperinsulinemia. GH therapy should be considered in lipodystrophic HIV-infected children with excess IAT.

Adolescent↗
PubMed2003

Increased lipodystrophy is associated with increased exposure to highly active antiretroviral therapy in HIV-infected children.

OBJECTIVE: To assess body composition changes in HIV-infected children receiving highly active antiretroviral therapy (HAART). METHODS: Thirty-seven HIV-positive children were enrolled. Dual-energy X-ray absorptiometry (DXA) scans were performed in all HIV-infected children at baseline and after an additional 12 months of HAART and in 54 matched (for sex, age, body mass index [BMI], and pubertal stage) healthy controls. Abdominal MRI was performed in 14 of 37 HIV-positive children at baseline and in 28 of 37 HIV-positive children after additional 12 months of HAART. RESULTS: During the study period, mean HAART exposure increased from 39.3 to 50.9 months and the number of HIV-infected children with clinical lipodystrophy (LD) increased from 6 to 8, whereas mean BMI, CD4 percentage, and percentage of HIV-infected children with HIV RNA <50 copies/mL did not change. DXA scans showed an increase in lean mass, peripheral fat loss, and central fat accumulation in all HIV-infected children. As compared with controls, 70% and 84% of HIV-infected children showed DXA-detectable LD at baseline and at 12 months of follow-up, respectively. Mixed LD and central fat accumulation were the most common LD phenotype. At baseline and at 12 months of follow-up, intra-abdominal adipose tissue (IAT) was greater than in controls in 33% and 35% of HIV-infected children, and it was greater in those with LD than in those without. Peripheral fat loss and IAT content were associated with duration of HAART and were independent of immunologic stage of disease and immunologic response. CONCLUSIONS: Changes in body composition related to LD in HAART-treated children are frequent, precocious, and progressive. Duration of HAART negatively influences visceral adiposity and peripheral fat loss.

Abdomen↗
PubMed2003

Hyperinsulinemia induced by highly active antiretroviral therapy in an adolescent with polycystic ovary syndrome who was infected with human immunodeficiency virus.

OBJECTIVE: To report a case of polycystic ovary syndrome (PCOS) in an adolescent infected with human immunodeficiency virus (HIV) and lipodystrophy whose insulin resistance was induced by highly active antiretroviral therapy (HAART). DESIGN: Case report. SETTING: Academic department of pediatrics. PATIENT(S): A 14-year-old vertically HIV-infected adolescent receiving HAART. INTERVENTION(S): Clinical observation, metabolic and endocrinologic assessment, imaging of ovaries by ultrasound, and of intra-abdominal adipose tissue content by magnetic resonance imaging. MAIN OUTCOME MEASURE(S): Lipodystrophy, insulin resistance, PCOS. RESULT(S): After 34 months of HAART this adolescent showed lipodystrophy with central obesity and insulin resistance after oral glucose tolerance test (OGTT). Ovaries were normal at ultrasonography. After 56 weeks of HAART, the adolescent showed more severe evidence of lipodystrophy and insulin resistance, and she developed acne, hirsutism, and amenorrhea. The following hormone levels were elevated: FSH 5.9 mUI/mL, LH 15.4 mUI/mL, LH/FSH ratio >2.5, free T 5.6 pg/mL, DHEAS 2,070 ng/mL, androstenedione (A) 3.42 ng/mL; whereas 17-beta-E(2), P, PRL, and free T(4) values were within the normal range. Ultrasonography demonstrated a typical polycystic echographic architecture of the ovaries. CONCLUSION(S): Lipodystrophy and insulin resistance are well-recognized side effects of HAART. Polycystic ovary syndrome might be an additional side effect secondary to insulin resistance and lipodystrophy.

Adolescent↗
PubMed2002

Mitochondrial functionality and mitochondrial DNA content in lymphocytes of vertically infected human immunodeficiency virus-positive children with highly active antiretroviral therapy-related lipodystrophy.

Mitochondria functionality and apoptosis were studied in peripheral blood lymphocytes (PBL) of human immunodeficiency virus type 1-infected children, with or without lipodystrophy (LD), who were receiving highly active antiretroviral therapy (HAART) and in PBL of healthy control subjects (HCs). By flow cytometry, mitochondrial (mt) membrane potential, mt mass, intra-mt cardiolipin distribution, and early and late apoptosis in fresh PBL or in PBL cultured with different stimuli were assessed. mtDNA content was evaluated in fresh PBL by an original double-competitive quantitative polymerase chain reaction method, which enabled direct quantification of the number of mtDNA copies present in human lymphocytes. PBL from LD-positive and LD-negative children and from HCs were similar in mt functionality and in their tendency to undergo apoptosis. mtDNA content was also similar in PBL of LD-positive children and HCs, suggesting that normal mt functionality and normal tendency to undergo apoptosis are present in PBL of children with HAART-associated LD.

Acquired Immunodeficiency Syndrome↗