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Carlo Giaquinto

Publications and source records attributed to Carlo Giaquinto.

At least 19 recordsLinked to original sources
PubMed2026

Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% &#x2265;3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

Humans↗
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

Long-term decay of the HIV-1 reservoir in HIV-1-infected children treated with highly active antiretroviral therapy.

To investigate the decay of the human immunodeficiency virus type 1 (HIV-1) reservoir in children receiving highly active antiretroviral therapy (HAART), we measured HIV-1 DNA in peripheral blood mononuclear cells from 14 children who achieved and maintained suppression of plasma viremia up to 48 months after the initiation of HAART. Levels of intracellular unspliced and multiply spliced HIV-1 RNA were used as markers of residual viral replication. During the first month of HAART, there were significant decays in levels of both plasma HIV-1 RNA and multiply spliced HIV-1 RNA, yet unspliced HIV-1 RNA persisted in most of the children. Greater HIV-1 DNA decay during the first month of HAART correlated with a higher concomitant increase in CD4(+) cell counts (P=.028) and a smaller subsequent HIV-1 DNA decay (P=.0012). Furthermore, HIV-1 DNA decayed faster from 1 to 9 months of HAART (median half-life, 5 months) than during the subsequent follow-up period (median half-life, 30 months). Moreover, after 9 months of HAART, HIV-1 DNA tended to decay more slowly in children with detectable levels of unspliced HIV-1 RNA. These findings suggest that clearance of the viral reservoir in HAART-treated children may be influenced by immune repopulation and residual viral replication and may help in refining long-term treatment strategies.

Adolescent↗
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

Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection.

OBJECTIVE: To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. METHODS: A multi-centre nationwide case-control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0-6.5 years). RESULTS: No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13-24 (P < 0.0001), 25-36 (P < 0.0001), and 37-48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P = 0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan-Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. CONCLUSION: The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

Age Factors↗
PubMed2006

Nosocomial rotavirus infection in European countries: a review of the epidemiology, severity and economic burden of hospital-acquired rotavirus disease.

The data currently available on the epidemiology, severity and economic burden of nosocomial rotavirus (RV) infections in children younger than 5 years of age in the major European countries are reviewed. In most studies, RV was found to be the major etiologic agent of pediatric nosocomial diarrhea (31-87%), although the number of diarrhea cases associated with other virus infections (eg, noroviruses, astroviruses, adenoviruses) is increasing quickly and almost equals that caused by RVs. Nosocomial RV (NRV) infections are mainly associated with infants 0-5 months of age, whereas community-acquired RV disease is more prevalent in children 6-23 months of age. NRV infections are seasonal in most countries, occurring in winter; this coincides with the winter seasonal peak of other childhood virus infections (eg, respiratory syncytial virus and influenza viruses), thus placing a heavy burden on health infrastructures. A significant proportion (20-40%) of infections are asymptomatic, which contributes to the spread of the virus and might reduce the efficiency of prevention measures given as they are implemented too late. The absence of effective surveillance and of reporting of NRV infections in any of the 6 countries studied (France, Germany, Italy, Poland, Spain and the United Kingdom) results in severe underreporting of NRV cases in hospital databases and therefore in limited awareness of the importance of NRV disease at country level. The burden reported in the medical literature is potentially significant and includes temporary reduction in the quality of children's lives, increased costs associated with the additional consumption of medical resources (increased length of hospital stay) and constraints on parents'/hospital staff's professional lives. The limited robustness and comparability of studies, together with an evolving baseline caused by national changes in health care systems, do not presently allow a complete and accurate overview of NRV disease at country level to be obtained. RV is highly contagious, and the efficiency of existing prevention measures (such as handwashing, isolation and cohorting) is variable, but low at the global level because of the existence of numerous barriers to implementation (eg, lack of staff, high staff turnover, inadequate hospital infrastructure). Prevention of RV infection by mass vaccination could have a positive impact on the incidence of NRV by reducing the number of children hospitalized for gastroenteritis, therefore reducing the number of hospital cross-infections and associated costs.

Child, Preschool↗
PubMed2006

Clinical trials of rotavirus vaccines in Europe.

Clinical trials of a live oral candidate rotavirus vaccine were started in 1982 and soon demonstrated that severe rotavirus disease can be prevented by vaccination. The first bovine candidate vaccine was withdrawn because of inconsistent efficacy, and studies of a rhesus rotavirus vaccine were initiated. A field trial of rhesus-human reassortant tetravalent rotavirus vaccine in Finland was pivotal for the licensure of this vaccine (RotaShield) in the United States in 1998. However, this vaccine was withdrawn in 1999 because of association with intussusception. Safety therefore became a major issue in the development of new candidate rotavirus vaccines. A pentavalent bovine-human reassortant rotavirus vaccine (RotaTeq) showed about 70% efficacy against any rotavirus disease and 100% efficacy against severe disease in Finland, according to the Clark scale. A large, multinational safety trial indicated no association of this vaccine with intussusception, and its licensure is under review in the EU. An attenuated human rotavirus vaccine (RIX4414; Rotarix) was developed from G1 rotavirus strain 89-12. A trial in Finland showed efficacy comparable with that of RotaShield, and a larger trial is under way in several European countries. In the first epidemic season, vaccine efficacy was 73% against any and 90% against severe rotavirus (mostly G1) gastroenteritis, according to the Vesikari scale. A large scale safety trial, conducted in Latin America plus Finland, indicated no increased risk of intussusception among recipients of Rotarix compared with placebo. The licensure of Rotarix is in process in the European Union.

Clinical Trials as Topic↗
PubMed2006

Economics of rotavirus gastroenteritis and vaccination in Europe: what makes sense?

Rotavirus is a major cause of gastroenteritis in children throughout Europe and the world. In addition to causing morbidity and mortality in children, rotavirus gastroenteritis (RVGE) creates a major economic burden on health care systems and families in Europe. The costs of hospital admissions for RVGE and nosocomial infections generate significant medical treatment costs throughout the region. Less information is available on the costs associated with less severe episodes and the costs borne by families, including lost time from work. The availability of rotavirus vaccines presents an effective opportunity to prevent RVGE and these associated economic costs, as well as providing protection to each child and hence benefiting the child's family. The adoption of rotavirus vaccine by health authorities in Europe will require a comparison of the costs and benefits. Economic evaluations that compare the costs of vaccination to the economic benefits of rotavirus vaccination will provide an estimate of its financial impact on health care systems and society. However, to provide a complete picture, economic evaluations of rotavirus vaccines will need to account for both the reduced costs and the reduced morbidity from prevented RVGE. Cost-effectiveness analyses based on quality-adjusted life years (QALYs) provide a systematic approach for assessing vaccination as a health investment, comparing the incremental costs associated with rotavirus vaccination and the reduced morbidity and mortality. QALYs provide a standardized approach for quantifying and comparing reductions in health-related quality of life and premature mortality. Although methodologic limitations exist in applying the QALY approach to childhood vaccines, their use in cost effectiveness analyses allows decision makers to consider the full health benefits of rotavirus and other vaccines.

Aged↗
PubMed2006

Rotavirus types in Europe and their significance for vaccination.

The degree of diversity of cocirculating human rotavirus wild-type strains is high. This article reviews the occurrence and frequency of rotavirus types in European children younger than 5 years of age during the past 10-15 years. To enable greater understanding of the overall epidemiologic situation, rotavirus types found in animals in Europe are described. In addition, rotavirus types occurring in children outside Europe are considered. Taken together, these data provide an essential background to the development of rotavirus vaccines. The different concepts of immunization with the 2 main rotavirus candidate vaccines are briefly discussed, and their potential impact on the epidemiology of cocirculating rotavirus wild-type viruses is considered. A case is made for comprehensive surveillance of cocirculating human rotavirus types in Europe after the implementation of rotavirus vaccination.

Age Distribution↗
PubMed2006

Intussusception among young children in Europe.

Intussusception, a potentially lethal condition with poorly understood etiology, is the most common cause of acute intestinal obstruction in children younger than 5 years old. In some cases, the condition has been associated with administration of the first licensed rotavirus vaccine, the reassortant rhesus-human tetravalent rotavirus vaccine (RRV-TV; RotaShield). No such association has to date been reported from large phase III safety trials with new rotavirus vaccines. As 2 new, live-attenuated oral rotavirus vaccines are currently under review for approval by the European Union regulatory authorities, a review of the clinical, etiologic and epidemiologic aspects of intussusception in Europe is urgently needed. We conducted a review of Medline literature, published from 1995 onwards on intussusception in the World Health Organization's European Region. The results are compared with data from previous reviews and other regions. The classic triad of intussusception symptoms (abdominal pain, abdominal mass, bloody stools) was present in 29-33% of patients according to the medical literature reviewed. Conservative treatment (barium, air or saline enema) was the rule (81% of cases), and few complications were observed during treatment. Treatment outcome was generally favorable, with recurrence occurring in approximately 1 in 10 patients, and only 1 death reported. Structural lead points were seen in 3% of patients; no other reliable data on the etiology of intussusception were found. The incidence of acute intussusception in young children in Europe, according to 6 heterogeneous hospital-based studies, ranged from 0.66 to 2.24 per 1000 children in inpatient departments and from 0.75 to 1.00 per 1000 children in emergency departments. Peak incidences were found in children 3-9 months of age. There are still gaps in our knowledge of intussusception with respect to its etiology and especially by which mechanisms RRV-TV might have caused it to occur. Data from regions outside Europe showed that rotavirus infection and disease are not associated with intussusception. As new rotavirus vaccines become available for use in Europe, postlicensure surveillance for intussusception is indicated and may be instrumental in further understanding the epidemiology of this condition and in further assessing the safety of future vaccines.

Child, Preschool↗
PubMed2006

Antiretroviral therapy for prevention of mother-to-child HIV transmission : focus on single-dose nevirapine.

Administration of potent antiretroviral combination therapy in the second and third trimester of pregnancy and during delivery, and for 6 weeks postpartum to the infant, may reduce HIV transmission from the mother to the child to <2% in formula-fed infants. In resource-constrained settings where women have limited access to antenatal care, use of shorter and more practical regimens, including nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs) commenced later in pregnancy, has demonstrated efficacies ranging from 18% to 70% in breast- and bottle-fed populations. Because shorter interventions include regimens such as single-dose nevirapine or zidovudine monotherapy, which do not provide maximal suppression of viral replication, emergence of resistant mutations in mother and infant occurs frequently, primarily after exposure to drugs with low genetic barriers (i.e. those requiring only one genotypic mutation to develop resistance), such as nevirapine. Different studies have reported nevirapine resistance rates ranging from 25% to 69% in mothers receiving single-dose nevirapine alone. Because NNRTI-based combinations of antiretroviral agents are recommended as first-line therapy in countries where single-dose nevirapine is the main option for preventing mother-to-child transmission of HIV, concerns have been raised as to whether single-dose nevirapine prophylaxis can compromise the efficacy of subsequent NNRTI-based antiretroviral therapy regimens. However, although some studies have shown that nevirapine exposure may impact on short-term virological outcome, the clinical relevance of nevirapine resistance remains unclear, especially in women who start treatment >6 months after delivery or in those who are not severely immunocompromised. Furthermore, studies have shown that adding short-course (up to 7 days) zidovudine or zidovudine/lamivudine prophylaxis after delivery may dramatically reduce the occurrence of nevirapine resistance in both mothers and infants. Until data are available that allow a better understanding of the relevance of antiretroviral drug resistance acquired as a result of mother-to-child HIV transmission prophylaxis, women and children who have previously received single- dose nevirapine as part of a mother-to-child transmission prevention strategy should be considered eligible for NNRTI-based regimens and should not be denied access to antiretroviral therapy.

Anti-HIV Agents↗
PubMed2005

Withdrawal of Pneumocystis jirovecii prophylaxis in HIV-infected children under highly active antiretroviral therapy.

OBJECTIVE: In HIV-infected adults Pneumocystis jirovecii pneumonia (PCP) prophylaxis can be safely withdrawn after immune reconstitution due to the introduction of highly active antiretroviral therapy (HAART). With regard to children only a small amount of data has been published. The present study investigated whether the withdrawal of PCP prophylaxis after immune reconstitution is safe in HIV-infected children. METHODS: A retrospective analysis at 10 European centers belonging to the Pediatric European Network on the treatment of AIDS (PENTA) using a standardized questionnaire. RESULTS: A total of 113 questionnaires were received. In 82 children the indication for PCP prophylaxis was provided following Centers for Disease Control (CDC) guidelines (72 primary and 10 secondary). Prophylaxis was withdrawn after the CD4 cell count increased above the age-related CDC thresholds. The observation period off prophylaxis was 335 years (300 years for primary and 35 years for secondary prophylaxis) and the median time per patient off prophylaxis was 4.1 years (range, 0.3-7.7 years). No episode of PCP occurred during the study period. In comparison with the incidence rate from historical data before the introduction of PCP prophylaxis and HAART, this was a significant reduction (P < 0.05). CONCLUSIONS: The increase in CD4 cell count provides functional reconstitution of the immune system in children. Our data suggests that the risk of developing a PCP after immune reconstitution is sufficiently low to withdraw PCP prophylaxis.

Adolescent↗
PubMed2005

Incidence of mucocutaneous reactions in children treated with niflumic acid, other nonsteroidal antiinflammatory drugs, or nonopioid analgesics.

BACKGROUND AND OBJECTIVE: Results from a relatively small case-control study recently showed that niflumic acid increases the risk of serious mucocutaneous reactions in children. As a consequence, the Italian Ministry of Health sent a "Dear Doctor" letter in June 2001 to warn pediatricians about the alleged adverse effects. The objective of this study was to estimate and compare the incidence of mild and severe mucocutaneous reactions among children using niflumic acid, other nonsteroidal antiinflammatory drugs (NSAIDs), or nonopioid analgesics. DESIGN: Retrospective cohort study. SETTING: Italy is one of the few countries in which a specific primary care system is devoted to children up to 14 years of age: every child is registered at birth and receives free medical care from 1 of the approximately 6000 family pediatricians working for the National Health Service. This study was conducted with the Pedianet network of Italian family pediatricians who use computerized electronic patient records for routine care; 185 pediatricians participated in the study. The patient records comprise information on demographics, diagnoses, symptoms, prescriptions, referrals, laboratory examinations, and hospitalizations. PARTICIPANTS: Children aged 0 to 14 years and registered with 1 of the collaborating pediatricians between January 1, 1998, and May 31, 2001. MAIN OUTCOME MEASURES: The incidence rate of severe (hospitalized or referred) and mild mucocutaneous reactions (exanthema, disseminated or localized pruritus, urticaria, angioedema, fixed eruption, dermatitis, erythema multiforme, vesicles, bullae, pustules, toxic epidermal necrolysis, purpura, and vasculitis) was estimated during use of niflumic acid, other NSAIDs, or nonopioid analgesics. For each episode of drug use, the following covariates were assessed: age, gender, region, year, indication for study drug, use of antibiotics, antimycotic agents, glucocorticoids, and other NSAIDs. Multivariate Poisson regression analysis was used to estimate the adjusted relative risk of mucocutaneous disorders during use of niflumic acid compared with use of other NSAIDs or use of acetaminophen alone. RESULTS: The population included 193727 children, 45351 of whom received at least 1 of the study drugs. The most frequently prescribed drugs were niflumic acid, acetaminophen, and propionic acid derivatives (ketoprofen and flurbiprofen). Users of niflumic acid (n = 32150) were younger and slightly more often had otitis media or upper respiratory tract infections as an indication compared with the other NSAIDs. During use of the various study drugs we identified 1451 mild mucocutaneous events and 42 severe reactions. The incidence rates of severe and mild mucocutaneous reactions after the administration of any study drug were 10.3 per 100000 exposure person-days and 3.7 per 1000 exposure person-days, respectively. Both incidence rates decreased strongly with increasing age. In comparison with other NSAIDs, the adjusted relative risks of niflumic acid were 0.5 (95% confidence interval: 0.23-1.27) for severe and 0.9 (95% confidence interval: 0.79-1.11) for mild mucocutaneous reactions. The use of acetaminophen as a reference category instead of other NSAIDs, restriction of the children to those who received NSAIDs for respiratory tract infections, or restriction to those who did not use antibiotics never revealed an increased risk of serious or mild mucocutaneous reactions during use of niflumic acid. CONCLUSIONS: In comparison with other NSAIDs or acetaminophen, niflumic acid is not associated with an increased risk of severe or mild mucocutaneous reactions in children. This was true for the different age groups and various types of mucocutaneous reactions, was independent of the concomitant use of antibiotics, and was not sensitive to changes in our assumptions regarding exposure and outcomes.

Adolescent↗
PubMed2005

Bayesian parameter estimates of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus type 1.

The objective of the present study was to develop a population pharmacokinetic model for nelfinavir mesylate (NFV) and nelfinavir hydroxy-tert-butylamide (M8), the most abundant metabolite of NFV, in infants vertically infected with human immunodeficiency virus type 1 and participating in the Paediatric European Network for Treatment of AIDS 7 study. Plasma NFV concentrations were determined during repeated NFV administrations (two to three times a day). Eighteen infants younger that age 2 years participated in this study. The doses administered ranged from 71 to 203 mg/kg of body weight/day. Pharmacokinetic parameter estimates were obtained by a compartmental approach by using a kinetic model to simultaneously fit NFV and M8 (active metabolite) concentrations. M8 was shown to be formation rate limited and was characterized by first-order rate constants of formation and elimination. Body weight was found to be a more appropriate predictor than age of the changes in (i) the rate of metabolism, (ii) the elimination rate constant of NFV, and (iii) NFV clearance. Population parameters were computed to account for the relationship between the rate of metabolism and body weight. The estimated NFV and M8 elimination half-lives were 4.3 and 2.04 h, respectively. The estimated NFV clearance was 2.13 liters/h/kg. The M8 concentration-to-NFV concentration ratio was 0.64 +/- 0.44. In conclusion, the population pharmacokinetic model describing the dispositions of NFV and M8 should facilitate the design of future studies to elucidate the relative contributions of the parent compound and M8 to the pharmacological and toxic effects of NFV therapy.

Aging↗
PubMed2004

Varicella vaccination in Italy : an economic evaluation of different scenarios.

AIM: To determine the economic impact (cost-benefit analysis) of childhood varicella vaccination, with the Oka/Merck varicella zoster virus vaccine live (Varivax) in Italy. METHODS: This analysis is based on an epidemiological model of varicella zoster virus (VZV) dynamics adapted to the Italian situation. Cost data (Euro, 2002 values) were collected through a literature review. Several vaccination scenarios were analysed: (i) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) without any catch-up programme; (ii) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) completed by a catch-up programme for 6-year-old children over the first 5 years of vaccine marketing; and (iii) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) completed by a catch-up programme during the first year of vaccine marketing for children aged 2-11 years. PERSPECTIVES: A societal perspective, including both direct and indirect costs, and a health-system perspective, limited to costs supported by Italian Health Authorities, were considered. RESULTS: A routine vaccination programme has a clearly positive impact on chickenpox morbidity. Respectively, 68% and 57% of chickenpox-related hospitalisations and deaths could be prevented with a 90% coverage rate. With vaccination costs being more than offset by a reduction in chickenpox treatment costs in the base case, such a programme could also induce savings from both a societal and a health-system perspective (40% and 12% savings, respectively for a 90% coverage rate). A lower coverage rate reduces cost savings, but there is still a 9% decrease in overall societal costs for a 45% coverage rate. Although the reduction in total societal costs was robust to the sensitivity analyses performed, a slight uncertainty remains regarding cost reduction from a health-system perspective. However, in this latter perspective, even in the worst-case scenario of the sensitivity analysis, routine vaccination programmes may be cost effective, the worst-case scenario for cost parameters leading to cost per life-year gained of Euro2853. Catch-up programmes combined with routine vaccination should lead to further cost reductions from a societal perspective: 15% for a massive catch-up during the first year of vaccine marketing compared with toddlers' vaccination alone, and 11% for a catch-up focused on 6-year-old children for a period of 5 years. However, the impact of catch-up programmes on the costs from an Italian health-system perspective remains close to zero (+/-1%). CONCLUSION: This model suggests, with its underlying assumptions and data, that routine ZVZ vaccination may be cost saving from both a societal and a health system perspective in the base case. In the worst-case scenario of the sensitivity analysis, vaccination remains cost effective.

Adolescent↗
PubMed2003

The incidence of varicella: correction of a common error.

BACKGROUND: Interest in the incidence of varicella (chickenpox) has increased since the discovery of an effective vaccine, but calculations to date have incorrectedly ignored the question of susceptibility. METHODS: We studied the occurrence of varicella in Italy on the basis of 33,343 children (age 0-14 years) cared for by 35 pediatricians between 1 October 1997 and 30 September 1998. The life-table technique was used to calculate the number of susceptible children. On this basis, we estimated the corrected age-specific and cumulative incidence. RESULTS: We identified 1749 cases among the estimated 21,783 susceptible children, for a crude incidence of 8.0% (95% confidence interval [CI] = 7.7-8.4). The rate age-standardized to the Italian population 0-14 years old was 6.8 (CI = 6.5-7.2). The incidence was more than 16% among children age 3-4 years and more than 4% for those age 1-10 years. Comparison of the usual method and our corrected method showed that the uncorrected method underestimates the crude annual incidence (5.2% 8.0%), shifts the peak incidence to earlier ages, and underestimates cumulative incidence (at age 14, 49% 67%). CONCLUSIONS: The use of our corrected method provides more valid estimates of the incidence of varicella than the ones that are currently available. Corrected estimates should be preferred to uncorrected ones in models to study the cost-effectiveness of universal vaccination against varicella.

Adolescent↗
PubMed2003

Pharmacokinetics of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus type 1.

BACKGROUND: In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population. METHODS: Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined. RESULTS: A mean nelfinavir daily dose of 135.7 +/- 18.8 mg/kg (twice or three times a day) resulted in median C(min), C(max), area under the plasma concentration-time curve (AUC(0-24 h)) and CL/ for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of C(max) and 27.8% of AUC(0-24 h) values were below the tenth percentile for adult values. CONCLUSIONS: During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.

Didanosine↗