Safety and Antiviral Response at 12 Months of Lopinavir/Ritonavir Therapy in Human Immunodeficiency Virus-1-Infected Children Experienced With Three Classes of Antiretrovirals
- 1 October 2005
- journal article
- clinical trial
- Published by Wolters Kluwer Health in The Pediatric Infectious Disease Journal
- Vol. 24 (10) , 867-873
- https://doi.org/10.1097/01.inf.0000180574.18804.90
Abstract
Many human immunodeficiency virus type 1 (HIV-1)-infected children have already failed treatment with 2 or even 3 classes of antiretrovirals. Coformulation of lopinavir with low dose ritonavir exhibits a potent antiretroviral effect. However, the data in heavily pretreated children are still scarce. This study evaluated the safety and effectiveness of combination therapy including lopinavir/ritonavir in children with prior exposure to all classes of oral antiretrovirals. This was an open label multicenter observational study, in which data were reviewed according to a standardized protocol. The study population included all HIV-1-infected children with virologic failure (HIV-1 RNA >5000 copies/mL) followed in 12 Spanish hospitals for >12 months, experienced with the 3 classes of oral antiretrovirals, in whom a lopinavir/ritonavir-containing regimen was started. By March 2003, 45 patients had been treated with lopinavir/ritonavir for a median of 18 months (range, 3-28). The median age at baseline was 9.7 years (range, 4.3-17.1). The median times of prior treatment were 88 months (range, 31-145) with nucleoside reverse transcription inhibitors and 42 months (range, 19-63) with protease inhibitors. Twenty-five patients were classified as Centers for Disease Control and Prevention clinical category C. Median values for absolute and percentage CD4 at baseline were 501 (range, 6-1512) and 19% (range, 0.5-49), respectively, and plasma HIV-RNA was 5.0 log10 copies/mL (range, 4.1-6.1). During follow-up, 11 (24%) children switched from liquid to solid formulation. At 48 weeks, the median values for absolute and percentage CD4 increased by 199 cells/microL and 3%, respectively, and median plasma viral load declined 1.75 log10 copies/mL. Forty-two percent of children achieved a plasma RNA of <400 copies/mL (intent to treat analysis). Baseline genotypic resistance was available in 40 children. Nonresponders had 7.0 +/- 1.6 protease inhibitor-associated mutations at baseline compared with 4.8 +/- 1.7 in children achieving virologic suppression (P = 0.06). Adverse events were described in 18 children. Three children permanently discontinued and 4 transiently withdrew lopinavir/ritonavir. At 12 months, there were mild but not significant increases in plasma cholesterol and triglycerides. Lopinavir/ritonavir when given as part of salvage regimen is well-tolerated, although switching to pills is frequently required. The regimen has a potent and durable antiretroviral activity in most heavily pretreated children, despite the presence of multiple mutations to all classes of oral antiretrovirals.Keywords
This publication has 20 references indexed in Scilit:
- Lopinavir Plasma Concentrations and Changes in Lipid Levels During Salvage Therapy with Lopinavir/Ritonavir-Containing RegimensJAIDS Journal of Acquired Immune Deficiency Syndromes, 2003
- Antiretroviral Drug Resistance Testing in Adults Infected with Human Immunodeficiency Virus Type 1: 2003 Recommendations of an International AIDS Society–USA PanelClinical Infectious Diseases, 2003
- High Variability of Plasma Drug Concentrations in Dual Protease Inhibitor RegimensAntimicrobial Agents and Chemotherapy, 2003
- Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected childrenThe Pediatric Infectious Disease Journal, 2003
- Metabolic complications of antiretroviral therapy in childrenThe Pediatric Infectious Disease Journal, 2003
- Lopinavir–Ritonavir versus Nelfinavir for the Initial Treatment of HIV InfectionNew England Journal of Medicine, 2002
- Nucleoside‐Analogue Reverse‐Transcriptase Inhibitors Plus Nevirapine, Nelfinavir, or Ritonavir for Pretreated Children Infected with Human Immunodeficiency Virus Type 1Clinical Infectious Diseases, 2002
- Safety and Antiviral Activity at 48 Weeks of Lopinavir/Ritonavir plus Nevirapine and 2 Nucleoside Reverse‐Transcriptase Inhibitors in Human Immunodeficiency Virus Type 1–Infected Protease Inhibitor–Experienced PatientsThe Journal of Infectious Diseases, 2002
- Randomized Study of Saquinavir with Ritonavir or Nelfinavir Together with Delavirdine, Adefovir, or Both in Human Immunodeficiency Virus–Infected Adults with Virologic Failure on Indinavir: AIDS Clinical Trials Group Study 359The Journal of Infectious Diseases, 2000
- Reduction in Mortality With Availability of Antiretroviral Therapy for Children With Perinatal HIV-1 InfectionJAMA, 2000