A Phase I/II Study of the Protease Inhibitor Ritonavir in Children With Human Immunodeficiency Virus Infection

Mueller, Brigitta U.; Nelson, Robert P.; Sleasman, John W.; Zuckerman, Judy; Heath-Chiozzi, Margo; Steinberg, Seth M.; Balis, Frank M.; Brouwers, Pim; Hsu, Ann; Saulis, Rima; Sei, Shizuko; Wood, Lauren V.; Zeichner, Steve; Katz, Tova; Higham, Colleen; Aker, Diane; Edgerly, Maureen; Jarosinski, Paul; Serchuck, Leslie; Whitcup, Scott M.; Pizzuti, David; Pizzo, Philip A.

doi:10.1542/peds.101.3.335

Cited by 92 publications

(44 citation statements)

References 27 publications

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“…The immediate treatment effects are most apparent with an improvement in weight and AMC; however, there was a trend toward a delayed response in height as well. The results of this study confirm previous research on the positive effect of PIs as a component of HAART in the reduction of viral load 2,16,17,[27][28][29] and with a larger cohort, confirm preliminary reports that suggest a positive effect of PIs on growth. 16,18,19,27,28,30,31 Other markers of nutrition, such as lean body mass, improved as well.…”

Section: Discussionsupporting

confidence: 91%

The Effect of Protease Inhibitor Therapy on Growth and Body Composition in Human Immunodeficiency Virus Type 1-Infected Children

Miller¹,

Mawn

Orav

et al. 2001

Pediatrics

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ABSTRACT. Objective. To determine the effect of protease inhibitors (PIs) on growth and body composition in children with human immunodeficiency virus type 1 (HIV-1) infection.Background. HIV-1-infected children have chronic problems with both linear growth and weight gain. Viral load may directly influence growth and nutritional status of HIV-1-infected children with reduction of viral load improving the nutritional condition.Design/Methods. Data from 67 patients who initiated PI therapy between 1996 and 1999 and who were enrolled in a prospective, longitudinal study of growth and nutrition in HIV-1-infected children were analyzed. Outcomes included pre-PI versus post-PI measures of height, weight, weight-for-height, triceps skinfold thickness, and arm muscle circumference. Predictor covariates included age, race, gender, Tanner stage, CD4 z score, Centers for Disease Control and Prevention stage, route of infection, plasma HIV-1 RNA, other antiretroviral therapy, recommended daily allowances for calories, treatment with megestrol acetate, and PI therapy.Results. Sixty-seven children were followed for a median of 2.4 years with a total of 362 visits (median: 5 visits; range: 1-12). During follow-up, they received PIs for a median of 5 months. Fifty-one percent were girls, 54% black, 15% Hispanic, and 25% white. The mean age at first visit was 6.8 years. In a univariate analysis, weight z score (؊0.67 to ؊0.35) and weight/height z score (0.25-0.76) improved on PI therapy. Using repeated-measures regression analysis, controlling for the above named covariates, PI treatment showed a significant effect on weight z score (increase in z score by 0.46), weight/height z score (increase in z score by 0.49), and arm muscle circumference (increase in percentile by 11.5). A borderline effect was found for height z score (increase in z score by 0.17) and no effect was found for triceps skinfold thickness. In a separate analysis, PI therapy increased CD4 counts twofold and reduced plasma HIV-1 RNA copies by 79%.Conclusion. In addition to a significant reduction in viral load, PI therapy in children has a positive effect on several growth parameters, including weight, weight/ height, and muscle mass. 1 Survival time and quality of life for children living in countries with access to highly active antiretroviral therapy (HAART) have improved because of advances in medical therapy. Indeed, the goal of therapy in the United States has shifted from delayed disease progression to indefinite viral suppression. 2-4 With these developments, new questions relating to longterm changes in growth and body composition in both adults and children have arisen.Understanding the link between nutrition and the new therapeutic options available is critical, because nutritional status has been shown to be associated with pediatric HIV-1 disease progression. 5,6 Growth patterns before HAART therapy of HIV-1-infected children in developed countries are fairly well established, 7-11 although the exact mechanisms of these growth abnormalities are n...

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Section: Discussionsupporting

confidence: 91%

The Effect of Protease Inhibitor Therapy on Growth and Body Composition in Human Immunodeficiency Virus Type 1-Infected Children

Miller¹,

Mawn

Orav

et al. 2001

Pediatrics

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“…In clinical trials, HAART has been shown to suppress viral load (VL) to less than the limits of detection and to increase the CD4+ T lymphocyte percentage in many İletişim/Correspondence to: Nasir Tajure Wabe, Jimma University P.O. Box 251 1480, Jimma, ETHIOPIA Tel: +251 911 68 0576 patients (14,15), with good outcomes overall (16,17). Results from observational studies suggest that at least 73.5% of patients initiating HAART achieve complete virological suppression within 6 months (18), but 9%-45% of patients do not experience an appropriate increase in their CD4 cell counts in the short term (19,20).…”

mentioning

confidence: 99%

“…While an increase in total CD4+ T lymphocytes is readily detectable, the ability to regenerate immunocompetent T-cell populations remains unresolved (21). Some clinical trials have demonstrated that the regenerated T cells consist predominantly of the memory (CD45RO+) type (14), while others have shown repopulation of naive (thymus-dependent, CD45RA+) T cells as well (22).…”

mentioning

confidence: 99%

Immunological and clinical progress of HIV-infected patients on highly active antiretroviral therapy in north west Ethiopia

Wabe¹,

Alemu²

2012

Gaziantep Med J

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The survival benefits of highly active antiretroviral therapy (HAART) in HIV infected patients have been studied well in the developed world. In resource poor settings like Ethiopia such treatment was started only in 2003. As a result, the existing treatment guidelines and recommendations are based on data from the developed world. The objective of this study was to determine the immunological and clinical progress in HIV/AIDS patients in one year data review of patients' card who initiated on HAART in Ethiopia. A retrospective cohort study was done based on past medical records of HIV/AIDS patients, using a structured data collection format. All patient cards of one year data with patients who initiated HAART from October 1, 2006 to November 30, 2007 were included in the study. The data collected was analyzed using SPSS for window version 16.0. The majority of the study population (383, 64.2%) were prescribed zidovudine/lamivudine/neverapine (ZDV/3TC/NVP) regimen initially. Overall functional status change showed that ability to work was increased by 31.5%, being ambulatory decreased by 93.4% and bedridden status decreased by 80%. A total of 240 (46.9%) patients have showed functional status improvement. Average mean weight change of 5.9 kg (increment by 11.9%) was seen during a one year follow-up. The patients showed immunological change from 132.883 mean CD4/mm 3 count to 335.87 mean CD4/mm 3 . About 492 (82.4%) patients present with different type of opportunistic infections (OIs) at start of therapy which dramatically dropped to only 40 (6.7%) patient after one year of receiving HAART. HAART initiation has decreased progression of the diseases and improved the patients' quality of life. Most patients have showed a significant increment in their CD4 count. The restoration of CD4 in turn has improved the clinical status of most patients. Despite the significant progression of health of patients, greater immunological and clinical success should be attained by encouraging patients for effective use of those lifesaving drugs with maximal adherence. 2) başlangıçta zidovudin/lamivudin/neverapin (ZDV/3TC/NVP) tedavisi verilmişti. Genelde fonksiyonel durum değişimi, çalışma yeteneğinin %31.5 arttığını, ayakta tedavi edilmenin %93.4 azaldığını, yatağa bağlı kalma durumunun %80 azaldığını gösterdi. Toplam 240 hasta fonksiyonel durum düzelmesi gösterdi. Bir yıllık izleme sırasında 5.9 kg ortalama ağırlık değişimi (%11.9 artma) gözlendi. Hastalar ortalama 132.883 CD4/mm 3 sayımından ortalama 335.87 CD4/mm 3 'e immünolojik değişim gösterdi. Tedavinin başlamasında farklı tipte fırsatçı enfeksiyonu bulunan yaklaşık 492 (%82.4) hasta, HAART tedavisi başlamasından bir yıl sonra dramatik olarak sadece 40'a (%6.7) düştü. HAART tedavisi başlanması hastalığın ilerlemesini azalttı ve hastaların yaşam kalitesini iyileştirdi. Hastaların çoğu CD4 sayılarında anlamlı artışlar gösterdi. CD4'deki düzelme birçok hastanın klinik durumunu iyileştirdi. Hastaların sağlığındaki anlamlı iyileşmeye karşın, hayat kurtaran bu ilaçlara d...

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“…1 To date, data regarding the disposition and drug interactions of nelfinavir (NFV) and other PIs in the pediatric population are limited. [2][3][4][5][6][7] We report the unique pharmacokinetic parameters of NFV dosed at a target of 27 to 33 mg/kg orally three times daily (TID), in the absence and presence of the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP), and dosed at a target of 55 mg/kg twice daily (BID) in clinically stable, antiretroviral-experienced patients who were aged 8 months to 16 years and enrolled in a large Pediatric AIDS Clinical Trials Group Protocol (PACTG) 377. PACTG 377 was designed to evaluate new combinations of potent antiretroviral agents.…”

mentioning

confidence: 99%

Nelfinavir Pharmacokinetics in Stable Human Immunodeficiency Virus-Positive Children: Pediatric AIDS Clinical Trials Group Protocol 377

et al. 2003

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ABSTRACT. Objective. Pharmacokinetic data obtained from children who have human immunodeficiency virus (HIV) infection are essential for the safe and effective use of antiretroviral agents in pediatric populations. The objective of this study was to assess the impact of body weight on the pharmacokinetic disposition of nelfinavir (NFV) in the absence and presence of nevirapine (NVP) and compare the pharmacokinetic profiles of twice-daily (BID) and three-times-daily (TID) NFV regimens.Methods. This was an intensive pharmacokinetic substudy nested in a phase II, multicenter, randomized, open-label trial. Forty-five HIV-infected children receiving NFV 30 mg/kg TID and 6 HIV-infected children receiving NFV 55 mg/kg BID were enrolled in this study and assigned to 1 of 4 stavudine-containing regimens, 3 containing NFV and 2 containing NVP. Area under the plasma concentration-time curves from 0 to 8 hours (AUC 0 -8 hours ) and from 0 to 12 hours (AUC 0 -12 hours ) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC 0 -24 hours was also calculated for each regimen.Results. NFV exposure in the absence of NVP was decreased in children who were <25 kg compared with those who were >25 kg (a 2.6-fold difference in median AUC 0 -8 hours ). NFV pharmacokinetics in the presence of NVP did not differ between the <25 kg and >25 kg groups. The AUC 0 -24 hours for children who were <30 kg and on NFV BID was comparable to the AUC 0 -24 hours for children who were >25 kg and on NFV TID but was 2.7-fold greater than AUC 0 -24 hours for children who were <25 kg and on NFV TID.Conclusions. NFV in the absence of NVP resulted in less than half the drug exposure in children who were <25 kg compared with children who were >25 kg. NFV dosed at 55 mg/kg BID in children who are <30 kg provides comparable exposure to that measured in children who are >25 kg and receiving NFV 30 mg/kg TID. Pediatrics 2003;112:e220 -e227. URL: http://www. pediatrics.org/cgi/content/full/112/3/e220; pharmacokinetics, nelfinavir, children, HIV, protease inhibitor, nevirapine.

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A Phase I/II Study of the Protease Inhibitor Ritonavir in Children With Human Immunodeficiency Virus Infection

Abstract: The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.

Cited by 92 publications

References 27 publications

The Effect of Protease Inhibitor Therapy on Growth and Body Composition in Human Immunodeficiency Virus Type 1-Infected Children

The Effect of Protease Inhibitor Therapy on Growth and Body Composition in Human Immunodeficiency Virus Type 1-Infected Children

Immunological and clinical progress of HIV-infected patients on highly active antiretroviral therapy in north west Ethiopia

Nelfinavir Pharmacokinetics in Stable Human Immunodeficiency Virus-Positive Children: Pediatric AIDS Clinical Trials Group Protocol 377

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