In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of ... more In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of morbidity and mortality. Clinical features of kidney damage in HIV-infected patients range from asymptomatic microalbuminuria to nephrotic syndrome. The lack of specific clinical features despite the presence of heavy proteinuria may mask the renal involvement. Indeed, it is important in HIV patients to monitor renal function to early discover a possible kidney injury. After the introduction of antiretroviral therapy, mortality and morbidity associated to HIV-infection have shown a substantial reduction, although a variety of side effects for long-term use of highly active antiretroviral therapy, including renal toxicity, has emerged. Among more than 20 currently available antiretroviral agents, many of them can occasionally cause reversible or irreversible nephrotoxicity. At now, three antiretroviral agents, i.e., indinavir, atazanavir and tenofovir disoproxil fumarate have a well estab...
Noncirrhotic portal hypertension is an uncommon liver disease of unknown origin, increasingly des... more 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.
An increasing prevalence of antiretroviral therapy (ART) resistance in ART-experienced and ART-na... more An increasing prevalence of antiretroviral therapy (ART) resistance in ART-experienced and ART-naive pregnant women has been reported. Some studies suggest that antiretroviral drug-resistant viruses might have decreased replication capacity and transmissibility. However, cases of perinatal transmission of multidrug-resistant HIV type-1 (HIV-1) have been described. Here, we report the case of one child with vertically-acquired multidrug-resistant HIV-1 and the outcome of a rescue therapy with a darunavir/ritonavir- and etravirine-containing antiretroviral regimen. During the 15 months of therapy, the child showed clinical improvement, including no side effects, persistent suppression of viral replication and a great increase in CD4+ T-cell count. Paediatric HIV specialists should be prepared to manage a small, but increasing, number of babies with a 'nightmare' multidrug-resistant virus with no available treatment options. The use of experimental agents might become a compell...
To assess the impact on immunological, virological and metabolic parameters of replacing protease... more 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. 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. 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 Gr...
Journal of acquired immune deficiency syndromes (1999), 2005
Short-term use of tenofovir (TDF) has been associated with bone mineral loss in adults and childr... more Short-term use of tenofovir (TDF) has been associated with bone mineral loss in adults and children. 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. 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. 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. Substitution to a TDF-containing antiretroviral regimen does no...
An antiretroviral regimen based on lamivudine+stavudine+protease inhibitor impairs peripheral fat... more An antiretroviral regimen based on lamivudine+stavudine+protease inhibitor impairs peripheral fat accrual in HIV-infected children and adolescents. We assess the effect on body composition parameters of replacing stavudine with tenofovir and protease inhibitor with efavirenz in paediatric patients. A 96-week prospective study on 24 patients, (age range: 5.0-17.9 years) with stable undetectable HIV-1 loads, who were switched from stavudine to tenofovir and from protease inhibitor to efavirenz. Patient assessment included: body composition parameters measured by dual-energy X-ray absorptiometry (DXA), viral load and CD4+ T-count and percentage. As a control group for DXA data, we studied 143 healthy controls (HCs; age range: 4.9-20.0 years). Virological suppression and unchanged CD4+ T-cell count and percentage were maintained in all patients. At baseline, patients showed decreased total, arm and leg fat masses (P < 0.01) but a similar trunk fat mass to HCs. From baseline to week 9...
Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development ... more Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development of safe and efficacious vaccines for HPV is a major public health concern. The two licensed HPV vaccines contain recombinant virus-like particles of HPV 16 and 18; one of such vaccines also protects against HPV types 6 and 11 which cause genital warts. We determined safety and immunogenicity of quadrivalent HPV vaccine in HIV-infected and HIV-negative adolescents and young adults, aged 13-27 years. The seroconversion rate, assessed by antibody titers, 1 month after the administration of the third vaccine dose was 0.85 (95% CI 0.75-0.95) in the HIV-infected group and 0.91 (0.83-0.99) in the HIV-negative subjects (p=0.52). The vaccine was generally safe and well tolerated; the most common side effect was local pain and the most frequent systemic side effect was headache. This is the first report on response to HPV vaccination in both female and male HIV-infected adolescents and young adults and highlights that this population may benefit from HPV immunoprophylaxis. Further studies are needed to examine the long term efficacy of this vaccine in HIV-infected individuals.
Reduced bone mineral density (BMD) and altered bone metabolism are common findings in HIV-infecte... more Reduced bone mineral density (BMD) and altered bone metabolism are common findings in HIV-infected patients. Increased bone formation has been described both in HIV-infected adults and children. Wnt ligands promote bone formation by stimulating osteoblast differentiation and their survival. Sclerostin and dickkopf factor 1 (DKK-1), Wnt antagonists, are important negative regulators of bone formation. We studied 86 HIV-infected patients whose ages ranged from 5.7 to 27.9 years. Patients were all on antiretroviral therapy, but seven who were naïve to treatment. Bone alkaline phosphatase (BAP), sclerostin, and DKK-1 were measured in serum by enzyme immunoassay. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and in the whole skeleton. Biochemical indexes were also measured in 143 healthy controls (age range 4.5-27.4 years). HIV-infected patients had lower than normal BMD (spine P < 0.005, and whole skeleton P < 0.03). BAP measurements were significantly h...
To evaluate long-term immunogenicity of a virosomal subunit inactivated influenza vaccine in chil... more To evaluate long-term immunogenicity of a virosomal subunit inactivated influenza vaccine in children with asthma, a prospective study was conducted during 2005-2006 influenza season in six public pediatric clinics in Milan and surroundings, Northern Italy. A single dose (0.5 ml) of a virosomal subunit inactivated influenza vaccine (Inflexal V ® ) was injected in 106 asthmatic children aged 3-9 years. Serum hemagglutinin inhibition antibody titers were determined against the recommended influenza strains A/New Caledonia (H1N1), A/California (H3N2), and B/Shanghai (B), at pre-vaccination and 1 and 6 months after vaccination. Seroconversion rate (95% CI) against the strains A/H1N1, A/H3N2 and B was, respectively, 78% (68.6-85.7), 57% (46.7-66.9) and 66% (55.8-71.2) at 1 month. Seroprotection (titer ≥ 40) rate for A/H1N1, A/H3N2 and B was, respectively, 87% (77.8-92.2), 82% (72.6-89.7) and 90% (82.6-94.8) at 1 month and 74% (64.3-82.3), 77% (67.5-84.8), and 77% (67.5-84.8) at 6 months. Seroprotection rate was high and persistent (>95%) in children with pre-existing antibodies (titer ≥ 10) at pre-vaccination for any specific strain. In children without pre-existing antibodies, seroprotection rate for A/H1N1, A/H3N2 and B was, respectively, 67.6%, 66.7% and 74.4% at 1 month, and 35.1%, 56.2% and 41.0% at 6 months after vaccination. Vaccine was well tolerated. These results indicate that in unvaccinated children with asthma vaccination with a single dose of virosomal-adjuvanted influenza vaccine is well tolerated and effective as a whole. However, while immunity response and persistence are excellently high in children with pre-existing antibodies, in children naive for the antigens the immune parameters are lower at 6 months after vaccination.
Journal of Maternal-Fetal and Neonatal Medicine, 2011
The rate of late preterm delivery has increased in the general population, and the late preterm i... more The rate of late preterm delivery has increased in the general population, and the late preterm infants have a higher incidence of morbidity compared to term newborns. Late preterm data are lacking in born to HIV-infected mother. We showed that, among 202 live births, late preterm delivery was higher in born to HIV-infected mothers than in the general population while their morbidity was lower.
Tenofovir disoproxyl fumarate is a known cause of kidney tubular dysfunction in HIV-infected pati... more 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 aim of the study was to examine temporal and geographical patterns of mode of delivery in the... more The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother-to-child transmission (MTCT).
Mother-to-child transmission of HIV infection occurred in a child born from an HIV-infected mothe... more Mother-to-child transmission of HIV infection occurred in a child born from an HIV-infected mother with HIV-RNA undetectable during pregnancy. She was suffering from gastroenteritis in the last 3 weeks of gestation.
In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of ... more In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of morbidity and mortality. Clinical features of kidney damage in HIV-infected patients range from asymptomatic microalbuminuria to nephrotic syndrome. The lack of specific clinical features despite the presence of heavy proteinuria may mask the renal involvement. Indeed, it is important in HIV patients to monitor renal function to early discover a possible kidney injury. After the introduction of antiretroviral therapy, mortality and morbidity associated to HIV-infection have shown a substantial reduction, although a variety of side effects for long-term use of highly active antiretroviral therapy, including renal toxicity, has emerged. Among more than 20 currently available antiretroviral agents, many of them can occasionally cause reversible or irreversible nephrotoxicity. At now, three antiretroviral agents, i.e., indinavir, atazanavir and tenofovir disoproxil fumarate have a well estab...
Noncirrhotic portal hypertension is an uncommon liver disease of unknown origin, increasingly des... more 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.
An increasing prevalence of antiretroviral therapy (ART) resistance in ART-experienced and ART-na... more An increasing prevalence of antiretroviral therapy (ART) resistance in ART-experienced and ART-naive pregnant women has been reported. Some studies suggest that antiretroviral drug-resistant viruses might have decreased replication capacity and transmissibility. However, cases of perinatal transmission of multidrug-resistant HIV type-1 (HIV-1) have been described. Here, we report the case of one child with vertically-acquired multidrug-resistant HIV-1 and the outcome of a rescue therapy with a darunavir/ritonavir- and etravirine-containing antiretroviral regimen. During the 15 months of therapy, the child showed clinical improvement, including no side effects, persistent suppression of viral replication and a great increase in CD4+ T-cell count. Paediatric HIV specialists should be prepared to manage a small, but increasing, number of babies with a 'nightmare' multidrug-resistant virus with no available treatment options. The use of experimental agents might become a compell...
To assess the impact on immunological, virological and metabolic parameters of replacing protease... more 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. 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. 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 Gr...
Journal of acquired immune deficiency syndromes (1999), 2005
Short-term use of tenofovir (TDF) has been associated with bone mineral loss in adults and childr... more Short-term use of tenofovir (TDF) has been associated with bone mineral loss in adults and children. 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. 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. 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. Substitution to a TDF-containing antiretroviral regimen does no...
An antiretroviral regimen based on lamivudine+stavudine+protease inhibitor impairs peripheral fat... more An antiretroviral regimen based on lamivudine+stavudine+protease inhibitor impairs peripheral fat accrual in HIV-infected children and adolescents. We assess the effect on body composition parameters of replacing stavudine with tenofovir and protease inhibitor with efavirenz in paediatric patients. A 96-week prospective study on 24 patients, (age range: 5.0-17.9 years) with stable undetectable HIV-1 loads, who were switched from stavudine to tenofovir and from protease inhibitor to efavirenz. Patient assessment included: body composition parameters measured by dual-energy X-ray absorptiometry (DXA), viral load and CD4+ T-count and percentage. As a control group for DXA data, we studied 143 healthy controls (HCs; age range: 4.9-20.0 years). Virological suppression and unchanged CD4+ T-cell count and percentage were maintained in all patients. At baseline, patients showed decreased total, arm and leg fat masses (P < 0.01) but a similar trunk fat mass to HCs. From baseline to week 9...
Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development ... more Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development of safe and efficacious vaccines for HPV is a major public health concern. The two licensed HPV vaccines contain recombinant virus-like particles of HPV 16 and 18; one of such vaccines also protects against HPV types 6 and 11 which cause genital warts. We determined safety and immunogenicity of quadrivalent HPV vaccine in HIV-infected and HIV-negative adolescents and young adults, aged 13-27 years. The seroconversion rate, assessed by antibody titers, 1 month after the administration of the third vaccine dose was 0.85 (95% CI 0.75-0.95) in the HIV-infected group and 0.91 (0.83-0.99) in the HIV-negative subjects (p=0.52). The vaccine was generally safe and well tolerated; the most common side effect was local pain and the most frequent systemic side effect was headache. This is the first report on response to HPV vaccination in both female and male HIV-infected adolescents and young adults and highlights that this population may benefit from HPV immunoprophylaxis. Further studies are needed to examine the long term efficacy of this vaccine in HIV-infected individuals.
Reduced bone mineral density (BMD) and altered bone metabolism are common findings in HIV-infecte... more Reduced bone mineral density (BMD) and altered bone metabolism are common findings in HIV-infected patients. Increased bone formation has been described both in HIV-infected adults and children. Wnt ligands promote bone formation by stimulating osteoblast differentiation and their survival. Sclerostin and dickkopf factor 1 (DKK-1), Wnt antagonists, are important negative regulators of bone formation. We studied 86 HIV-infected patients whose ages ranged from 5.7 to 27.9 years. Patients were all on antiretroviral therapy, but seven who were naïve to treatment. Bone alkaline phosphatase (BAP), sclerostin, and DKK-1 were measured in serum by enzyme immunoassay. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and in the whole skeleton. Biochemical indexes were also measured in 143 healthy controls (age range 4.5-27.4 years). HIV-infected patients had lower than normal BMD (spine P < 0.005, and whole skeleton P < 0.03). BAP measurements were significantly h...
To evaluate long-term immunogenicity of a virosomal subunit inactivated influenza vaccine in chil... more To evaluate long-term immunogenicity of a virosomal subunit inactivated influenza vaccine in children with asthma, a prospective study was conducted during 2005-2006 influenza season in six public pediatric clinics in Milan and surroundings, Northern Italy. A single dose (0.5 ml) of a virosomal subunit inactivated influenza vaccine (Inflexal V ® ) was injected in 106 asthmatic children aged 3-9 years. Serum hemagglutinin inhibition antibody titers were determined against the recommended influenza strains A/New Caledonia (H1N1), A/California (H3N2), and B/Shanghai (B), at pre-vaccination and 1 and 6 months after vaccination. Seroconversion rate (95% CI) against the strains A/H1N1, A/H3N2 and B was, respectively, 78% (68.6-85.7), 57% (46.7-66.9) and 66% (55.8-71.2) at 1 month. Seroprotection (titer ≥ 40) rate for A/H1N1, A/H3N2 and B was, respectively, 87% (77.8-92.2), 82% (72.6-89.7) and 90% (82.6-94.8) at 1 month and 74% (64.3-82.3), 77% (67.5-84.8), and 77% (67.5-84.8) at 6 months. Seroprotection rate was high and persistent (>95%) in children with pre-existing antibodies (titer ≥ 10) at pre-vaccination for any specific strain. In children without pre-existing antibodies, seroprotection rate for A/H1N1, A/H3N2 and B was, respectively, 67.6%, 66.7% and 74.4% at 1 month, and 35.1%, 56.2% and 41.0% at 6 months after vaccination. Vaccine was well tolerated. These results indicate that in unvaccinated children with asthma vaccination with a single dose of virosomal-adjuvanted influenza vaccine is well tolerated and effective as a whole. However, while immunity response and persistence are excellently high in children with pre-existing antibodies, in children naive for the antigens the immune parameters are lower at 6 months after vaccination.
Journal of Maternal-Fetal and Neonatal Medicine, 2011
The rate of late preterm delivery has increased in the general population, and the late preterm i... more The rate of late preterm delivery has increased in the general population, and the late preterm infants have a higher incidence of morbidity compared to term newborns. Late preterm data are lacking in born to HIV-infected mother. We showed that, among 202 live births, late preterm delivery was higher in born to HIV-infected mothers than in the general population while their morbidity was lower.
Tenofovir disoproxyl fumarate is a known cause of kidney tubular dysfunction in HIV-infected pati... more 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 aim of the study was to examine temporal and geographical patterns of mode of delivery in the... more The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother-to-child transmission (MTCT).
Mother-to-child transmission of HIV infection occurred in a child born from an HIV-infected mothe... more Mother-to-child transmission of HIV infection occurred in a child born from an HIV-infected mother with HIV-RNA undetectable during pregnancy. She was suffering from gastroenteritis in the last 3 weeks of gestation.
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