{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:31:28Z","timestamp":1784194288019,"version":"3.55.0"},"reference-count":26,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,3,1]]},"abstract":"<jats:p>Objective. Simplification of antiretroviral regimen in human immunodeficiency virus (HIV)-infected children has not yet been investigated. In general, children have a more difficult time maintaining viral suppression because of many factors, including frequent nonadherence and less availability of antiretrovirals in palatable forms. In addition, many serious metabolic complications have emerged in HIV-infected adults and are believed to be attributable to antiretroviral therapy. Some of these complications\u2014hypercholesterolemia, hypertriglyceridemia, and insulin resistance\u2014are believed to be the result of the use of protease inhibitor (PI) therapy, whereas the cause of others, such as lipodystrophy, remains undetermined. Recent reports underline that children experience long-term metabolic abnormalities in the same manner that adults do, and perhaps these consequences are even more worrisome in children secondary to long-term expected survival. We report here the results of the first open-label PI-switch study in HIV-infected children.<\/jats:p>\n               <jats:p>Methods. Seventeen children, 24 to 160 months of age (median: 120), were enrolled into the study. All were receiving a stable PI-containing antiretroviral regimen that containing 2 to 3 nucleoside analogue reverse transcriptase inhibitors (NRTIs) in addition to 1 to 2 PIs for a median duration of 21 months (range: 5\u201350) before study entry. All children had HIV-1 RNA &amp;lt;400 copies\/mL at screening; their baseline plasma HIV-1 RNA level had been &amp;lt;400 copies\/mL for a median of 13 months (range: 4\u201355) before study entry. All patients were nai\u0308ve to nonnucleoside reverse transcriptase inhibitor therapy. Their protease inhibitor(s) was switched to efavirenz while their NRTI therapy was maintained.<\/jats:p>\n               <jats:p>Results. All children were heavily pretreated; 88% of the patients had previous NRTIs, and 41% had previous PI use. The most common PI at study entry was nelfinavir (47%), followed by ritonavir (29%), then amprenavir (18%); only 1 was on saquinavir\/ritonavir. At study entry, the duration of previous antiretroviral therapy was between 21 and 123 months (median: 88). All patients completed the 48-week study. No acquired immunodeficiency syndrome\u2013defining events occurred. There were no rashes and no changes in liver transaminases. Mild, transient insomnia and dizziness each occurred in 1 child. Two other subjects (6 and 8 years old) experienced unusual vivid dreams, mostly pleasant, which decreased in intensity and frequency after the first 12 weeks of the study. One subject, a 10-year-old girl, had an episode of generalized seizure at week 6; study drugs were not interrupted, and seizure never recurred. The patient had a strong family history of epilepsy, although she had never experienced previous seizures. No anticonvulsants were given. Sixteen of 17 patients had HIV-1 RNA levels of &amp;lt;50 copies\/mL (1 HIV-1 RNA was 61 copies\/mL) at week 48. The mean CD4% remained stable initially from a mean of 35.1% (\u00b12.8%) at baseline to 36.8% (\u00b15%) at week 24, but increased to 38% (\u00b16%) at week 48. Fasting triglycerides decreased from a mean of 126 mg\/dL (\u00b150) at baseline to 86 mg\/dL (\u00b145) at week 24 and to 94 mg\/dL (\u00b138) at week 48. At study entry, 12 (71%) of 17 children had triglyceride levels greater than the 95th percentile for age, race, and gender, compared with only 6 (35%) of 17 at week 48. Fasting cholesterol levels decreased from a mean of 203 mg\/dL (\u00b150) at baseline to 173 mg\/dL (\u00b131) at week 24 and to 174 mg\/dL (\u00b127) at week 48. At study entry, 5 (29%) of 17 children had cholesterol levels greater than the 95th percentile for age, race, and gender, compared with only 1 (6%) of 17 at week 48. The decrease in low-density lipoprotein cholesterol was also significant, from a mean baseline of 124 mg\/dL (\u00b142) to 100 mg\/dL (\u00b128) at week 24 and to 105 mg\/dL (\u00b120) at week 48. High-density lipoprotein (HDL) cholesterol did not change significantly, but the changes in cholesterol:HDL ratio, a better marker of atherogenic risk, significantly decreased from a mean baseline of 3.8 (\u00b10.8) to 3.2 (\u00b10.7) at week 24 and to 3 (\u00b10.6) at week 48. Detailed dietary history revealed no significant changes during the study. In addition, none of the patients initiated therapy with lipid-lowering agents. There were no significant changes in insulin or C-peptide throughout the study period. In addition, anthropometric measurements that included mid-thigh and mid-arm circumferences, triceps and thigh skinfolds, and waist:hip ratio were stable throughout the study period. For bioelectrical impedance measurements, lean body mass increased from a mean baseline of 32.1 lb (\u00b19.3) to 35.7 lb (\u00b111.4) at week 24 and to 36.5 lb (\u00b111.5) at week 48. Bioelectrical impedance measurements of fat content were unchanged throughout the study period.<\/jats:p>\n               <jats:p>Conclusion. This is the first study in children to evaluate the substitution of PI in a virologically successful regimen with efavirenz, a potent once-daily nonnucleoside reverse transcriptase inhibitor therapy. We were able to show significant improvement in fasting total cholesterol, low-density lipoprotein cholesterol, triglycerides, and, more important, the cholesterol:HDL ratio. In addition, switching to an efavirenz-containing regimen was well tolerated and successfully maintained virologic suppression in all HIV-infected children in this study. This study should encourage large randomized trials to investigate simplification strategies in HIV-infected children.<\/jats:p>","DOI":"10.1542\/peds.111.3.e275","type":"journal-article","created":{"date-parts":[[2004,8,14]],"date-time":"2004-08-14T00:43:47Z","timestamp":1092444227000},"page":"e275-e281","source":"Crossref","is-referenced-by-count":67,"title":["Impact of Protease Inhibitor Substitution With Efavirenz in HIV-Infected Children: Results of the First Pediatric Switch Study"],"prefix":"10.1542","volume":"111","author":[{"given":"Grace","family":"McComsey","sequence":"first","affiliation":[{"name":"Rainbow Babies and Children\u2019s Hospital, Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasreen","family":"Bhumbra","sequence":"additional","affiliation":[{"name":"Medical College of Ohio, Toledo, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Fu","family":"Ma","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Plainsboro, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mobeen","family":"Rathore","sequence":"additional","affiliation":[{"name":"University of Florida Health Science Center, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Alvarez","sequence":"additional","affiliation":[{"name":"University of Florida Health Science Center, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2003,3,1]]},"reference":[{"key":"2021121101565913500_R1","doi-asserted-by":"crossref","unstructured":"Palella FJ, Delaney KM, Moorman AC, et al. 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Effect of ritonavir and post-heparin lipase activities in normal subjects. AIDS.2000;14:51\u201357","DOI":"10.1097\/00002030-200001070-00006"},{"key":"2021121101565913500_R5","doi-asserted-by":"crossref","unstructured":"Noor MA, Lo JC, Mulligan K, et al. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS.2001;15:F11\u2013F18","DOI":"10.1097\/00002030-200105040-00001"},{"key":"2021121101565913500_R6","unstructured":"Powderly WG. The strategy of antiretroviral switch studies: a review. Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17\u201320, 2000; Toronto, Ontario, Canada. Abstract 1375"},{"key":"2021121101565913500_R7","doi-asserted-by":"crossref","unstructured":"Martinez E, Garcia-Viejo MA, Blanco JL, et al. Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy. 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Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine or to efavirenz in patients with human immunodeficiency virus infection and long-lasting viral suppression. Clin Infect Dis.2002;34:504\u2013510","DOI":"10.1086\/324629"},{"key":"2021121101565913500_R11","doi-asserted-by":"crossref","unstructured":"Hirschel B, Flepp M, Bucher HC, et al., and the Swiss HIV Cohort. Switching from protease inhibitors to efavirenz: differences in efficacy and tolerance among risk groups: a case-control study from the Swiss HIV cohort. AIDS.2002;16:381\u2013385","DOI":"10.1097\/00002030-200202150-00009"},{"key":"2021121101565913500_R12","unstructured":"Melvin A, Lennon S, Mohan K, Purnell J. Blood lipid levels and body composition in HIV-infected children treated with protease inhibitors. Program and abstracts of the 7th Conference of Retroviruses and Opportunistic Infections; January 30\u2013February 4, 2000; San Francisco, CA"},{"key":"2021121101565913500_R13","unstructured":"Lee CL, Johann-Liang R. Hypercholesterolemia and protease inhibitors in HIV-infected pediatric population. Program and abstracts of the 37th Annual Meeting of the Infectious Disease Society of America; November 18\u201321, 1999; Philadelphia, PA. Abstract"},{"key":"2021121101565913500_R14","doi-asserted-by":"crossref","unstructured":"Arpadi SM, Cuff P, Horlick M, Wang J, Kotler D. Lipodystrophy in HIV-infected children is associated with high viral load and low CD4+-lymphocyte count and CD4+-lymphocyte percentage at baseline and use of protease inhibitors and stavudine. J Acquir Immune Defic Syndr.2001;27:30\u201334","DOI":"10.1097\/00042560-200105010-00005"},{"key":"2021121101565913500_R15","doi-asserted-by":"crossref","unstructured":"Jaquet D, Le\u0301vine M, Ortega-Rodriguez E, et al. Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children. AIDS.2000;14:2123\u20132128","DOI":"10.1097\/00002030-200009290-00008"},{"key":"2021121101565913500_R16","doi-asserted-by":"crossref","unstructured":"Babl FE, Regan AM, Pelton SI. Abnormal body-fat distribution to HIV-1 infected children on antiretrovirals. Lancet.1999;353:1243\u20131244","DOI":"10.1016\/S0140-6736(98)05754-7"},{"key":"2021121101565913500_R17","doi-asserted-by":"crossref","unstructured":"Amaya RA, Kozinetz CA, McMeans A, et al. Lipodystrophy syndrome in human immunodeficiency virus-infected children. Pediatr Infect Dis J.2002;21:405\u2013410","DOI":"10.1097\/00006454-200205000-00011"},{"key":"2021121101565913500_R18","doi-asserted-by":"crossref","unstructured":"Christensen B, Glueck C, Kwiterovich P, et al. Plasma cholesterol and triglycerides in 13,665 children and adolescents: the prevalence study of the lipid research clinics program. 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