Valeria Manfredini

University of Milan, Milano, Lombardy, Italy

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Publications (18)48.5 Total impact

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    ABSTRACT: Tenofovir disoproxyl fumarate is a known cause of kidney tubular dysfunction in HIV-infected patients. Recent studies reported significant association between specific allelic variants in ABCC2, ABCC4 and/or ABCC10 genes and the development of kidney tubular dysfunction in HIV-infected adults. We describe the first 2 cases of vertically HIV-infected patients affected by kidney tubular dysfunction associated with polymorphisms in the ABCC genes.
    The Pediatric Infectious Disease Journal 10/2013; 32(10):e403-5. · 3.57 Impact Factor
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    ABSTRACT: Treatment with antiretroviral agents (ARVs) during pregnancy is important to prevent mother-to-child transmission of the human immunodeficiency virus (HIV), but their use has been associated with low bone mineral density in adult patients. Currently, there are no data regarding the bone status of HIV-infected women who received ARV during pregnancy. The aim of this study was to evaluate cortical bone status at delivery in a group of HIV-infected women who received ARV during pregnancy and to monitor the changes occurring during the first year postpartum. We studied 33 HIV-infected and 116 HIV-uninfected healthy Caucasian women within 4 days from delivery. Follow-up measurements were performed at 4 and 12 months postpartum in 17 HIV-infected and 55 healthy women. Cortical bone status was evaluated by quantitative ultrasonography at the mid-tibia, and bone measurements were expressed as the speed of sound (SOS). HIV-infected women after delivery had a median SOS of 3,985 (3,567-4,242) m/s, while the median SOS of healthy women was 4,025 (3,643-4,250) m/s. The difference was not significant (t = 0.39, P = 0.69). No significant differences were observed between ARV-exposed and control subjects at 4 and 12 months. Our data suggest that ARV during pregnancy and the first year after delivery does not affect negatively cortical bone status.
    Calcified Tissue International 01/2013; · 2.75 Impact Factor
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    ABSTRACT: Purpose of the study: Vertical transmission of HIV can be almost eliminated by an appropriate combination of preventative measures, which include the use of combination antiretroviral therapy (ARV) during pregnancy, elective cesarean delivery, and avoidance of breastfeeding. Although current ARV demonstrated to be very effective to control virus infection, it has numerous side effects, including negative repercussions on bone mass. Currently there are no data regarding the bone status of HIV-infected women who received ARV during pregnancy. The aim of this study was to evaluate cortical bone status at delivery in a group of HIV-infected women who received ARV during pregnancy, to monitor the changes occurring during the first year post-partum and to compare the results with those obtained in healthy mothers. Methods: We studied 17 HIV-infected and 55 HIV-uninfected healthy women within 3 days from delivery, at 4 and 12 months postpartum (median age 36.4 years). The majority (68%) of the HIV-infected mothers was on ARV containing two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI), and 16% was on a regimen containing two NRTIs and two PIs. Other ARV regimens included the use of two NRTIs and one non-NRTI (10%), one NRTI plus one PI (3%), or two NRTIs and three PIs (3%). The median (range) exposure to ARV during gestation was 14 (5-35) weeks. The great majority (91%) of the women showed an undetectable viral load (<50 cp/mL) at delivery. Median CD4 number at delivery was 610 (128 to 1415). Cortical bone status was evaluated by quantitative ultrasonography at the mid-tibia, and bone measurements were expressed as the speed-of-sound (SOS). Summary of results: HIV-infected women after delivery had a median SOS of 3985 (3567-4242) m/s, while the median SOS of healthy women was 4025 (3643-4250). The difference was not significant (t=0.39; P=0.69). SOS measurements at baseline, at 4, and at 12 months are shown in Table 1. SOS values did not change significantly in the HIV-infected mothers' group (F=0.02; P=0.88), while they changed over time in the healthy mothers' group (F=0.15; P=0.02). No significant differences were observed between ARV-exposed and control subjects at 4 and 12 months. Conclusion: Our data suggest that ARV during pregnancy and the first year after delivery does not affect negatively cortical bone status and that QUS results are equivalent to those of HIV-negative healthy women.
    Journal of the International AIDS Society 11/2012; 15(6):18320. · 3.94 Impact Factor
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    ABSTRACT: Purpose of the study: Besides its known effects on bone metabolism, vitamin D may regulate immune function. We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and modulate immune responses in HIV-infected children and youth. Methods: Caucasian vertically HIV-infected patients (aged 8 to 26 years) with vitamin D deficiency and normal parathormone (PTH) levels were randomized into an experimental (n=25) and control (n=25) group to receive 100,000 IU of oral cholecalciferol every 3 months for a total of 4 doses, or placebo. A pre-randomization period (-3 months) was also taken into account to better model within-individual variability. Mixed linear regression models were used to evaluate the between-group changes in the outcomes of interest. The analysis was intention to treat. Summary of results: 47 subjects completed the RCT. Cholecalciferol supplementation produced an early decrease in PTH levels (3 months) and a later concomitant increase in 25(OH)D and 1,25(OH)2D levels (6 months), both persisting up to 12 months.The supplementation had no effect on CD4(+)T-cell numbers or percentage while was associated with a decreased loge Th1, an increased loge Th2 (*p<0.05), an increased loge Treg (**p<0.01), and and a decreased loge Th17:Treg(*p<0.05). Conclusions: In our cohort, supplementation with oral cholecalciferol was effective in increasing serum 25(OH)D and 1-25(OH)2D while decreasing serum PTH levels, had no effect on CD4(+)T-cell count, but was associated with T-cell phenotype changes mainly favoring Tregulatory subset.
    Journal of the International AIDS Society 11/2012; 15(6):18231. · 3.94 Impact Factor
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    ABSTRACT: Noncirrhotic portal hypertension is an uncommon liver disease of unknown origin, increasingly described in HIV-infected adults. Prolonged antiretroviral exposure, in particular to didanosine, and thrombophilic predisposition have been suggested as potential pathogenic factors. Data are limited in children. We describe a 10-year-old HIV-infected girl with noncirrhotic portal hypertension who presented with progressive spleen enlargement and variceal bleeding.
    The Pediatric Infectious Disease Journal 07/2012; 31(10):1059-60. · 3.57 Impact Factor
  • G V Zuccotti, V Fabiano, V Manfredini
    Early human development 05/2012; 88 Suppl 2:S84-5. · 2.12 Impact Factor
  • Pediatrics International 04/2012; 54(2):311-2. · 0.88 Impact Factor
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    Hepatitis Monthly 03/2012; 12(3):211-2. · 1.25 Impact Factor
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    ABSTRACT: The use of combined antiretroviral agents during pregnancy is important to prevent mother-to-child transmission of human immunodeficiency virus (HIV). Antiretroviral treatment (ARV) is associated with reduced bone mass and altered bone metabolism in HIV-infected patients. There are no data regarding the effect of ARV exposure during pregnancy on newborns and infants. We therefore studied 38 subjects born from HIV-infected mothers, and we measured the speed-of-sound (SOS) at the tibia by quantitative ultrasonography (QUS) just after birth. QUS measurements at mid-tibia is easily performed in infants with the appropriate probe. Nevertheless, at this skeletal site only cortical bone is present, and therefore QUS measurements reflect the status of only one kind of bone tissue. We also measured bone alkaline phosphatase (BAP) and C-terminal telopeptide of type I collagen (CTX) in the cord blood as bone formation and resorption markers, respectively. SOS measurements were repeated at 4 and 12 months of age. As a control group we studied 94 subjects born from HIV-negative mothers. At birth the median (range) SOS of ARV-exposed neonates was 3006 (2870-3168) m/s, while that of control subjects was 3007 (2757-3311) m/s. The difference was not significant. BAP concentration of ARV-exposed was 103.6 (31.6-182.8) U/L, not different from that of control subjects (104.4 [43.2-227.2] U/L). CTX concentrations were 1.07 (0.26-2.8) ng/mL, and 1.38 (0.34-4.2) ng/mL in ARV-exposed and control subjects, respectively. SOS measurements at 4 months and 12 months of age were available for 17 ARV-exposed subjects and for 57 control subjects. SOS values changed significantly over time in both groups (F=6.1; P<0.0001). No differences were present between ARV-exposed and control subjects at 4 and 12 months. Our study suggests that ARV exposure during intrauterine life does not affect negatively bone metabolism and bone development, and that the changes occurring in bone QUS measurements during the first year of life in ARV-exposed subjects are similar to those occurring in healthy control infants.
    Bone 11/2011; 50(1):255-8. · 4.46 Impact Factor
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    ABSTRACT: Few data are available on the safety and long-term immunogenicity of A/H1N1 pandemic influenza vaccines for HIV-infected pediatric patients. We performed a randomized controlled trial to evaluate the safety and long-term immunogenicity of 1 versus 2 doses of the 2009 monovalent pandemic influenza A/H1N1 MF59-adjuvanted vaccine (PV) coadministered with the seasonal 2009-2010 trivalent nonadjuvanted influenza vaccine (SV) to HIV-infected children, adolescents, and young adults. A total of 66 HIV-infected patients aged 9 to 26 years were randomized to receive one (group 1) or two (group 2) doses of PV coadministered with 1 dose of SV. The main outcome was the seroconversion rate for PV at 1 month. Secondary outcomes were the geometric mean titer ratios and the seroprotection rates at 1 month for all vaccines, seroconversion rates at 1 month for SV, and longitudinal changes of antibody titers (ABTs) at 1, 2, 6, and 12 months for all vaccines. Groups 1 and 2 had similar CD4 counts and HIV RNA levels during the study. The seroconversion rate for PV was 100% at 1 month in both groups. ABTs for PV were high during the first 6 months and declined below seroprotection levels thereafter. Longitudinal changes in ABTs were similar in groups 1 and 2 for both PV and SV. The side effects of vaccination were mild and mostly local. In HIV-infected children, adolescents, and young adults, the immune response triggered by a single dose of PV was similar to that obtained with a double dose and was associated with long-term antibody response.
    Clinical and vaccine Immunology: CVI 07/2011; 18(9):1503-9. · 2.60 Impact Factor
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    ABSTRACT: Availability of highly active antiretroviral therapy has dramatically increased survival rates and substantially modified the course of HIV infection, which has now become a chronic disease both in adults and in children. Treatment strategies in paediatric patients have to face with specific challenges associated with selection of a successful antiretroviral drug regimen, long-lasting maintenance of adherence to therapy, short and long-term drug-related toxicities and emerging of extensive drug resistance. This review shows an up-to-date picture of the ultimate advances of antiretroviral therapy in HIV-infected children.
    Pharmacological Research 07/2011; 64(1):1-3. · 4.35 Impact Factor
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    ABSTRACT: Growth impairment and bone toxicity due to tenofovir disoproxil fumarate (TDF) fetal exposure has been described mainly in animals. We evaluated growth pattern and bone health in TDF-exposed HIV-uninfected children born to HIV-infected mothers, defined as seroreverters (SR). This was a multicentre observational cross-sectional cohort study enrolling 68 SR who were in utero exposed to an antiretroviral regimen including (TDF+) or not including (TDF-) tenofovir. Neonatal data and duration of antiretroviral exposure were recorded. At enrolment, anthropometric measures, tibial speed of sound (SOS) by quantitative ultrasound and several parameters of bone metabolism were assessed. Gestational age and median in utero antiretroviral exposure were similar in subjects exposed to TDF (n=33) and those non-exposed (n =35). Age at enrolment was comparable in the two groups (TDF-exposed range 11.8-76.2 months and TDF non-exposed range 11.8-77.9 months). The incidence of low weight and length measurements (<10th percentiles) at birth was similar in TDF-exposed and TDF non-exposed. Normal growth development was found in both groups of subjects at enrolment. The median (0.6; range -2.4-2.6) SOS z-score of TDF-exposed was similar to the median (0.8; range -2.2-4.4) SOS z-score of TDF non-exposed (Student's t=0.84; P=0.40). Parameters of bone metabolism were similar in the two groups. Exposure to TDF during pregnancy does not impair growth patterns, bone health and markers of bone metabolism in SR infants and young children born to HIV-infected women.
    Antiviral therapy 01/2011; 16(8):1259-66. · 3.07 Impact Factor
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    ABSTRACT: Sporadic cases of renal toxicity have been reported in HIV-infected children treated with tenofovir disoproxil fumarate (TDF). We assessed the long-term renal safety of TDF in a cohort of vertically HIV-infected children, adolescents and young adults. We evaluated 26 HIV-infected children, adolescents and young adults, aged 4.9-17.4 years at baseline, every 6 months for 60 consecutive months. At the baseline visit, they had an undetectable viral load and a good immune reconstitution and were being treated with lamivudine, stavudine and a protease inhibitor (PI). At the same visit, stavudine was replaced with TDF and the PI with efavirenz. Serum creatinine, estimated glomerular filtration rate (GFR), urine protein to creatinine ratio, serum phosphate, ratio of the maximum rate of tubular phosphate reabsorption to the GFR (TmPO(4)/GFR), urine glucose, and urine α(1)-microglobulin to creatinine ratio were used as markers of renal function. The outcome-time relationships were studied using generalized estimating equations (GEEs). In addition to time (continuous, ten equally spaced intervals), sex, age at baseline and CD4+ T-cell count were used as covariates. A moderate reduction in GFR was observed only once in an underweight female patient. There was no occurrence of proteinuria, hypophosphataemia or glycosuria. Moreover, TmPO(4)/GFR was stable and the urine α(1)-microglobulin to creatinine ratio was always within normal limits. TDF had an excellent renal safety profile in HIV-infected children, adolescents and young adults regularly followed up for 60 months.
    Clinical Drug Investigation 01/2011; 31(6):407-15. · 1.70 Impact Factor
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    ABSTRACT: Reduced bone mass measurements are often found in HIV-infected youths. Both in vitro and human studies demonstrated a role of antiretroviral treatment in determining bone mass alteration. Nevertheless, the data regarding the responsibility of different antiretroviral drugs on bone health in children and adolescents are highly controversial. The purpose of the current study was to relate antiretroviral treatment to bone mass measurements in a large cohort of HIV-infected children and adolescents. Bone mineral content (BMC) was measured in 86 HIV-infected youths (aged 4.8-22.1 years), and in 194 healthy controls (aged 4.9-21.9 years). Fifteen patients were naive to antiretroviral treatment, 11 were receiving a dual nucleoside reverse transcriptase inhibitor (NRTIs) combination, 32 a protease inhibitor (PI)-based antiretroviral treatment, and 28 a non-nucleoside reverse transcriptase inhibitor (NNRTIs)-based regimen. Comparisons between healthy and HIV-infected children and adolescents have been performed by multiple regression analyses to correct for differences in age, sex, and anthropometric measurements. Patients receiving a PI-based treatment had lumbar spine and whole body BMC values significantly lower than healthy children (P<0.05). BMC measurements of patients on other therapeutic regimens or naive to antiretroviral treatment did not differ significantly from those of healthy children. Among patients receiving a PI-based regimen, those receiving full dose Ritonavir had significantly lower lumbar spine BMC values compared to other patients. Lumbar spine and whole body BMC measurements of patients receiving a Stavudine-containing regimen were lower compared to healthy controls, naive patients, and patients on other antiretroviral regimens. Multivariate analyses showed that patients receiving both Stavudine and full dose Ritonavir had significantly lower BMC values both at the lumbar spine (P=0.0033), and in the whole skeleton (P=0.05). In conclusion, antiretroviral treatment may have a detrimental effect on bone health of HIV-infected youths: the use of Ritonavir full dose alone or in combination with Stavudine is associated to lower bone mass measurements. The use of antiretroviral regimens including these drugs should thus be monitored closely in HIV-infected youths.
    Bone 03/2010; 46(6):1633-8. · 4.46 Impact Factor
  • CROI, San Francisco; 02/2010
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    ABSTRACT: An 8-year-old girl was presented to our department for persistent diarrhoea. A first diagnosis of tuberculosis, along with the result of the chest x-ray scan, had been posed some months before, after a holiday in Brazil, when she started presenting aspecific systemic and gastrointestinal symptoms. The girl was under specific antitubercular treatment when we first saw her. New diagnosis of schistosomiasis was posed by our laboratory tests. Treatment with praziquantel was started and complete resolution of clinical and radiological picture was observed.
    Case Reports 01/2010; 2010.
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    ABSTRACT: The objective of this study was to construct reference ranges of the neonatal cerebellar vermis height with respect to the gestational age at birth. This observational study assessed 434 neonates born at 25-42 weeks' gestation. The neonates were singleton and appropriate in size for gestational age, and did not exhibit any abnormalities or neonatal disease. Gestational age was based on the date of the last menstrual period and confirmed by ultrasound examination performed within the 12(th) week of pregnancy. Sonographic measurements of the height of the cerebellar vermis in the mid-sagittal plane were performed within 24 h of birth by the same neonatal sonographer. Reference ranges (5(th), 50(th) and 95(th) centiles) were estimated by a mean and SD model based on least-squares polynomial regression. Neonatal sonographic measurements were obtained in all cases. Mean (SD) maternal age was 30.2 (4.3) years. Mean cerebellar vermis height adjusted for gestational age did not differ between males and females, the mean adjusted difference being 0.012 (95% CI, - 0.009 to 0.033) cm. Mean cerebellar vermis height (cm) against gestational age (weeks) was suitably modeled by a linear-cubic polynomial as - 1.784 + 0.137 x GA - 0.000019 x GA(3) (SD = - 0.147 + 0.008 x GA), where GA = gestational age. Reference ranges for the height of the cerebellar vermis at birth with respect to gestational age at birth have been constructed in appropriate-for-gestational-age neonates.
    Ultrasound in Obstetrics and Gynecology 05/2008; 31(4):401-5. · 3.56 Impact Factor
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    ABSTRACT: Objectives: In addition to its known effects on bone metabolism, vitamin D may regulate immune function. Design: We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and affect the T-cell phenotype in HIV-infected youth with vitamin D insufficiency. Methods: Fifty-two HIV-infected patients aged 8 to 26 years and with serum 25(OH) D <30 ng/mL were randomized to receive orally vitamin D3 100,000 IU or placebo every 3 months for 4 doses. Serum 25(OH)D, 1,25(OH)2D, PTH, and CD4+ T cells were assessed 3 months before baseline and at 0, 3, 6, 9, and 12 months, while Th1-, Th2-, Th17-, and Treg-subsets and T-lymphocyte vitamin D receptor were assessed at 0, 3, and 12 months. Results: Forty-eight subjects (25 receiving vitamin D and 23 receiving placebo) completed the RCT. Cholecalciferol supplementation produced an early (3 months) decrease in PTH, a concomitant increase in 25(OH)D, and a later (6 months) increase in 1,25(OH)2D levels, all persisting at 12 months. The frequency of vitamin D insufficiency at 12 months was 20% versus 60% in the intervention versus placebo group (P = .007). Cholecalciferol supplementation had no effect on CD4+ T-cell counts but was associated with a decreased Th17:Treg ratio at 3 months. Conclusions: In our cohort of HIV-infected youth, a 12-month cholecalciferol supplementation increased 25(OH)D and 1-25(OH)2D and decreased PTH levels but had no effect on CD4+ T-cells. However, it was associated with changes in CD4+ T-cell phenotype, warranting further investigation.
    HIV Clinical Trials 14(2):51-60. · 2.30 Impact Factor