Combination Therapy with Efavirenz, Nelfinavir, and Nucleoside Reverse-Transcriptase Inhibitors in Children Infected with Human Immunodeficiency Virus Type 1

Starr, Stuart E.; Fletcher, Courtney V.; Spector, Stephen A.; Yong, Florence H.; Fenton, Terence; Brundage, Richard C.; Manion, Douglas J.; Ruíz, Nancy; Gersten, Merril; Becker, Mark; McNamara, James; Mofenson, Lynne; Purdue, Lynette; Siminski, Suzanne; Graham, Bobie; Kornhauser, David M.; Fiske, William D.; Vincent, Carol; Lischner, Harold W.; Dankner, Wayne M.; Flynn, Patricia M.

doi:10.1056/nejm199912163412502

Cited by 198 publications

(149 citation statements)

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“…4,5 Diarrhea was reported for 18% of participants in a trial of a nelfinavir-based regimen. 6 In our study, approximately one fourth of all children experienced very mild or greater nausea/vomiting/abdominal pain, loss of appetite, and/or diarrhea. Although PI therapy was associated with greater gastrointestinal symptoms, only diarrhea differed significantly between treatment groups.…”

Section: Discussionmentioning

confidence: 49%

“…1,2 Clinical trials have demonstrated the effectiveness of PI combination therapy (PI therapy) in decreasing plasma HIV RNA levels, although the proportion of children with virologic suppression to undetectable levels is generally smaller than the corresponding proportion of adults. [3][4][5][6] Antiretroviral regimens including PIs have been shown to increase CD4 ϩ cell counts, even for children with advanced disease, [4][5][6][7][8][9] and studies are now beginning to document their effects on clinical outcomes. Baseline and treatment-mediated changes in immunologic and virologic markers were independent predictors of survival in a meta-analysis of pediatric antiretroviral clinical trials, and virologic markers predicted weight growth and cognitive failure among children Ͼ1 year of age.…”

mentioning

confidence: 99%

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Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

Storm¹,

Boland²,

Gortmaker

et al. 2005

Pediatrics

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ABSTRACT.Objectives. This study examines quality of life (QOL) among school-aged children with perinatally acquired HIV infection and compares QOL outcomes between treatment groups that differ according to the use of protease inhibitor (PI) combination therapy (PI therapy). To gain insights into how PI therapy might influence QOL, associations between severity of illness and QOL were also investigated.Methods. Cross-sectional data for 940 children, 5 to 18 years of age, who were enrolled in Pediatric AIDS Clinical Trials Group Late Outcomes Protocol 219 were used to examine domains of caregiver-reported QOL, as assessed with the General Health Assessment for Children, during 1999. The General Health Assessment for Children is an age-specific, modular, QOL assessment that was developed for the study with previously validated measures. QOL differences between treatment groups were estimated with linear and logistic regressions that controlled for sociodemographic characteristics (age, gender, race/ethnicity, maternal/caregiver education, and respondent) and severity-of-illness indicators related to receipt of PI therapy (AIDS status, log 10 CD4 ؉ cell counts, and height-for-age z scores).Results. The mean age of participants was 9.7 years. Most children were non-Hispanic black (54%) or Hispanic (31%), and 49% of the participants were female. At the 1999 study visit, ϳ14% of children had severe immune suppression (<15% CD4 ؉ cells), whereas 62% of children had >25% CD4 ؉ cells, ie, no immune suppression. Participants did exhibit some lag in growth, with mean height and weight z scores of ؊0.70 and ؊0.20, respectively. Twenty-eight percent of the children were reported to have met criteria for AIDS at study entry (1993)(1994)(1995)(1996)(1997)(1998)(1999). When treatment groups were compared, children receiving PI therapy (72%) were older, had lower CD4 ؉ cell percentages, and had lower height and weight z scores than did those receiving non-PI therapies. They were also more likely to have met criteria for AIDS at study entry. The most commonly used PIs were ritonavir (46%) and nelfinavir (63%). Health perceptions ratings for most children were at the upper end of the scale, whereas ratings for 25% of the children ranged over the lower 70% of scale scores. Almost one half of the children had at least some limitations in physical functioning, with more frequent limitations in energydemanding activities (46%) than in basic activities of daily living (32%). The Behavior Problems Index was used to assess psychologic functioning. The mean total Behavior Problems Index score (9.34) and the proportion of children with extreme scores (23%) were consistent with values reported for chronically ill children and those at social and economic risk. One or more limitations in social/school functioning were reported for 58% of children. More than one third of the children (38%) experienced >1 physical symptoms that were at least moderately distressing. Health perceptions, physical functioning, psychologic functioning, social/school...

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Section: Discussionmentioning

confidence: 49%

mentioning

confidence: 99%

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

Storm¹,

Boland²,

Gortmaker

et al. 2005

Pediatrics

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“…Despite the widening scope of using ART (29), HIVinfected children still less frequently reach undetectable HIV-RNA viral load than adults (14)(15)(16). It is mandatory to enquire about the underlying reasons for such discrepancy and so far few studies have assessed the immunologic characteristics of pediatric patients, especially those who show a good response to therapy.…”

Section: Discussionmentioning

confidence: 99%

HIV‐1‐infected children on HAART: Immunologic features of three different levels of viral suppression

Zaccarelli-Filho¹,

Ono²,

Machado³

et al. 2006

Cytometry Part B Clinical

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Background: HIV-1-infected children show changes of blood lymphocyte subpopulations. We have, therefore, investigated how highly active anti-retroviral therapy (ART) alter these subsets. Blood samples were taken from 41 HIV-1-infected children on ART who were divided into groups showing good, partial and poor responses to ART on the basis of viral load (VL) measurement in blood. The observations were compared to those seen in 20 uninfected children.Methods: The samples were studied using 4-color flow cytometry for ''naïve'', central memory and effector memory cells as well as for CD38 expression as the sign of activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected children were also evaluated for the presence and the titers of antibodies induced by vaccination against childhood infections in our patients while on HAART.Results: Lymphocyte counts were lower in the \poor" viral load responding (VLR) group when compared with partial and good VLRs. Poor VLRs had lower total and naïve CD4+ T cell counts. HIV-1-infected children from all three groups had high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were particularly low in the poor VLR group while in the poor VLR group the percentages of effector memory CD4+ and CD8+ T cells were higher when compared with the control group. Higher cellular activation of CD8+ T cells was observed in HIV-1-infected children, particularly when analyzed for the intensity of CD38 expression in the poor VLR group. CD5 expression on B cells was higher among all HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and hepatitis B were present in a large proportion of children but the titers were similarly low for all three groups of HIV-infected children.Conclusions: Children with different levels of viral response to HAART present immune phenotype characteristics that tend to place the children with partial and good virological responses into the same group. These children are still moderately deficient in their immune responses but show better recovery than seen with children in the poor VLR group. These observations indicate that the proportions of central memory cells among the CD4+ T cells and the intensity of the expression of CD38 activation antigen on CD8+ T cells provide more informative parameters for monitoring children on HAART than the absolute numbers of CD4+ and CD8+ T cells alone. q

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“…Peak EFV plasma concentrations are reached 3 -5h after a single oral dose and become steady at 6 -7 days (Maggiolo, 2009). An important pharmacokinetic inter-individual variability has been reported in patients taking EFV: a daily dose of 600mg usually results in a C max of 12.9 ± 3.7M and a C min of 5.6 ± 3.2M (Starr, 1999;Staszewski, 1999), but higher levels (between 30 -50M) have been observed in as many as 20% of patients (Marzolini, 2001;Burguer, 2006). This drug is extensively biotransformed into inactive hydroxylated metabolites via the cytochrome P450 system, and CYP2B6 is likely to be the corresponding isoenzyme.…”

Section: Efavirenzmentioning

confidence: 99%

Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity

Blas‐García¹,

Apostolova²,

Esplugues³

2011

Recent Translational Research in HIV/AIDS

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Combination Therapy with Efavirenz, Nelfinavir, and Nucleoside Reverse-Transcriptase Inhibitors in Children Infected with Human Immunodeficiency Virus Type 1

Abstract: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.

Cited by 198 publications

References 19 publications

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

HIV‐1‐infected children on HAART: Immunologic features of three different levels of viral suppression

Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity

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