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One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.

Assuntos

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Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts /=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.

Assuntos

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OBJECTIVES: To describe varicella complications in healthy and previously ill children hospitalized for varicella and to explore trends in group A beta-hemolytic streptococcus complications of varicella. METHODS: A retrospective record review of children hospitalized for varicella between January 1, 1990, and March 31, 1994, was conducted in nine large acute care hospitals in Los Angeles County, California. RESULTS: We identified 574 children hospitalized for varicella in study hospitals during the 4.25-year study period (estimated risk of hospitalization, approximately 1 in 550 cases of varicella); 53% of the children were healthy before the onset of varicella and 47% were previously ill with underlying cancers or other chronic illnesses. Children were hospitalized for treatment of complications (n = 427, 74%) or for prophylactic antiviral therapy or observation (n = 147, 26%). Systems involved in complications included skin/soft tissue (45%), neurologic (18%), respiratory (14%), gastrointestinal (10%), and hematologic, renal, or hepatic (8% or less). The mean age of children with skin/soft tissue infections was 2.7 years (range < 1 to 16 years) compared with 4.7 years (< 1 to 18 years) for other complications. Children with skin/soft tissue and neurologic complications were more often previously healthy (p < 0.05), whereas those with respiratory complications were more often previously ill (p < 0.001). Hospitalizations for skin/soft tissue infections increased during the study period. The proportion of complications as a result of group A beta-hemolytic streptococcus infection increased from 4.7% before 1993 to 12.2% for the remainder of the study period (p = 0.02). CONCLUSIONS: Prior health status was predictive of the type of complications experienced by children with varicella requiring hospitalization. Our data suggest a recent increase in skin/soft tissue complications of varicella requiring hospitalization and an increase in the proportion of complications related to group A beta-hemolytic streptococcus. Wide-scale vaccine use should reverse this trend and reduce the overall impact of varicella on both healthy and previously ill children.

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OBJECTIVE: To examine complications and treatment of varicella-zoster virus (VZV) infections in children infected with human immunodeficiency virus type 1 (HIV-1). METHODS: Cases of VZV infection were identified retrospectively by reports to the department of health services and review of medical charts. The CD4+ cell counts were correlated with severity and frequency of VZV episodes. RESULTS: We identified 117 episodes of VZV infection in 73 HIV-1-infected children between Aug. 21, 1986, and Dec. 1, 1993. The most common complications were recurrence and persistence; 38 children (53%) had 69 recurrent episodes of VZV infection. The majority of children (61%) had zoster during the first recurrent episode, and 32% had a disseminated eruption typical of varicella. There was a strong association between an increasing number of episodes of VZV infection and low CD4+ cell count (p = 0.0008). In a subgroup followed for at least 2 years after their primary varicella episode, 10 of 22 children had a recurrence. Persistence of VZV infection was documented in 10 of 73 children, whereas other complications were rare. Thirty-three children (45%) were hospitalized and received acyclovir intravenously. CONCLUSION: Primary, recurrent, and persistent VZV infections are a frequent cause of morbidity and hospitalization for HIV-1-infected children. Studies of improved preventive and therapeutic agents are urgently needed in this population.

Assuntos

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As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m2 per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0 mumol.hr per liter at the 180 mg/m2 level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications for the future utility of therapeutic drug monitoring with these agents.

Assuntos

Assuntos