MOAB0101 - Oral Abstract Session
A randomized study comparing low dose versus standard dose lopinavir/ritonavir among HIV-infected children with virological suppression
Presented by Thanyawee Puthanakit (Thailand).
T. Puthanakit1,2, P. Suntarattiwong3, P. Sangkla4, P. Kosalaraksa5, C. Ngampiyaskul6, P. Srisamang7, S. Kanjanavanit8, J. Wongsawat9, W. Petdachai10, W. Chatchomchuan11, N. Lertpienthum12, J. Sophonphan1, J. Ananworanich1,13,14
1HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand, 2Chulalongkorn University, Department of Pediatrics, Faculty of Medicine, Bangkok, Thailand, 3Queen Sirikit National Institute of Child Health, Bangkok, Thailand, 4Surin Hospital, Surin, Thailand, 5Khon Kaen University, Department of Pediatrics, Faculty of Medicine, Khon Kaen, Thailand, 6Prapokklao Hospital, Chantaburi, Thailand, 7Sappasitthiprasong Hospital, Ubonratchathani, Thailand, 8Nakornping Hospital, Chiang Mai, Thailand, 9Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, 10Phrachomklao Hospital, Petchaburi, Thailand, 11Udonthani Hospital, Udonthani, Thailand, 12Buddhachinaraj Hospital, Phitsanulok, Thailand, 13Chulalongkorn University, Faculty of Medicine, Bangkok, Thailand, 14SEARCH, Thai Red Cross AIDS Research Center, Bangkok, Thailand
Background: Lopinavir/ritonavir is associated with dyslipidemia. Published data showed adequate lopinavir/ritonavir Ctrough when 70% of the standard dose was used. Here, we hypothesized that by using 70% of lopinavir/ritonavir standard dose for maintenance therapy, virological efficacy would be maintained and dyslipidemia reduced, compared to using standard dose.
Methods: We conducted a multicentre, randomised, open-label trial at 11 sites in Thailand. HIV-infected children aged < 18 years weighing 25-50 kg and had HIV RNA (VL) < 50 copies/ml were randomly assigned by minimization scheme to FDA -recommended standard dose of lopinavir/ritonavir heat stable tablet or low dose (70% standard dose). LPV/r dosages for children 25-35 kg were 300/75 mg or 200/50 mg, children >35-50 kg were 400/100 mg or 300/75 mg twice daily. The primary endpoint was proportion of children with VL < 50 copies/ml at week 48. Secondary endpoints were lopinavir Ctrough and dyslipidemia.(ClinicalTrials.gov number, NCT01307124)
Findings: From June to December 2011, 200 children, with mean (SD) age of 13.1 (2.5) years, and CD4 of 818 (312) cells/mm3 were randomly assigned to standard (n=99) or low dose arm (n=101). The NRTI backbone were zidovudine/lamivudine (47%), zidovuidne/didanosine (17%), tenofovir/lamivudine (16%) and others (20%). By intention to treat analysis, proportions of children with VL < 50 copies/ml at week 48 were 91.8% and 88.1%, difference -3.7% (95% CI; -12.0% to 4.6%). By per protocol analysis, proportions of children with VL < 50 copies/ml at week 48 were 93.7% and 91.8%, difference -1.9%(95% CI; -9.4 % to 5.5% ). Mean (SD) lopinavir Ctrough were 7.1(3.7) and 5.2(2.4) mg/dl, respectively. Fourteen (7.3%) had Ctrough < 1 mg/dl (4 in standard and 10 in low dose arms, p = 0.1). More children in the standard arm had cholesterol > 200 mg/dl (34.4% vs. 20.6%, p=0.03) and triglyceride > 150 mg/dl (60.4% vs. 44.3%, p =0.03) than those in the low dose arm.
Conclusion: This study demonstrated noninferiority in virological efficacy of low dose compared to standard dose lopinavir/ritonavir tablet as maintenance therapy. Dyslipidemia was less with low dose. This dosing regimen conferred adequate LPV blood level with reduce drug cost and potential long term complications.
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