Safety and Antiviral Response at 12 Months of Lopinavir/Ritonavir Therapy in Human Immunodeficiency Virus-1-Infected Children Experienced With Three Classes of Antiretrovirals

Ramos, JT; Mi, de José Gómez; Dueñas, Joaquín; Fortuny, Clàudia; Gonzalez-Montero, Raul; Mj, Mellado Peña; Mur, Antonio; Navarro, Marisa; Otero, Carmen; Pocheville, I; Ma, Muñoz-Fernández; Cabrero, Esther

doi:10.1097/01.inf.0000180574.18804.90

Cited by 19 publications

(14 citation statements)

References 23 publications

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“…We found that nearly half of them achieve virological response after rescue interventions. Our result are similar to other studies which also have been carried among children in real life situations [8,12]. …”

Section: Discussionsupporting

confidence: 93%

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Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

Larrú

Mendoza²,

Bellón

et al. 2007

BMC Infect Dis

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BackgroundThe impact of HIV drug resistance mutations in salvage therapy has been widely investigated in adults. By contrast, data available of predictive value of resistance mutations in pediatric population is scarce.MethodsA multicenter, retrospective, observational study was conducted in children who received rescue salvage antiretroviral therapy after virologic failure. CD4 counts and viral load were determined at baseline and 6 months after rescue intervention. Genotypic HIV-1 resistance test and virtual phenotype were assessed at baseline.ResultsA total of 33 children met the inclusion criteria and were included in the analysis. The median viral load (VL) and median percentage of CD4+ at baseline was 4.0 HIV-RNA log copies/ml and 23.0% respectively. The median duration that children were taking the new rescue regimen was 24.3 weeks (23.8–30.6). Overall, 47% of the 33 children achieved virological response at 24 weeks. When we compared the group of children who achieved virological response with those who did not, we found out that mean number of PI related mutations among the group of responders was 3.8 vs. 5.4 (p = 0.115). Moreover, the mean number of susceptible drugs according to virtual phenotype clinical cut-off for maximal virologic response was 1.7 vs. 0.8 and mean number of susceptible drugs according to virtual phenotype cut-off for minimal virlologic response was 2.7 vs. 1.3 (p < 0.01 in all cases). Eighteen children were rescued with a regimen containing a boosted-PI and virological response was significantly higher in those subjects compared with the others (61.1% vs. 28.6%, p < 0.01).ConclusionSalvage treatment containing ritonavir boosted-PIs in children with virological failure was very efficient. The use of new tools as virtual phenotype could help to improve virologic success in pediatric population.

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Section: Discussionsupporting

confidence: 93%

“…[7-9]. However, the extended use of PIs as salvage therapy for heavily pre-treated subjects has not fulfilled its expectations [10-12]. Moreover, there are few studies available concerning predictive factors of virological success when PIs/rit are used in a second or third-line of HAART in this special population [7,13].…”

Section: Introductionmentioning

confidence: 99%

Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

Larrú

Mendoza²,

Bellón

et al. 2007

BMC Infect Dis

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“…19 In another cohort of 45 PI-experienced children treated with LPV/r-based HAART, 42% had VL Ͻ400 copies/mL at 48 weeks. 20 The children in these previously mentioned studies were less sick than ours; fewer had AIDS and their median CD4% was much higher. In general, they were similar in age and baseline VL to our patients.…”

Section: Discussionmentioning

confidence: 81%

Double Boosted Protease Inhibitors, Saquinavir, and Lopinavir/Ritonavir, in Nucleoside Pretreated Children at 48 Weeks

Kosalaraksa

Bunupuradah²,

Engchanil³

et al. 2008

Pediatric Infectious Disease Journal

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“…The recommended doses for children who weigh more than 15 kg are 10 mg/kg of body weight or 230 mg/m 2 (body surface area) twice daily, with a maximum of 400 mg per dose unless it is combined with drugs affecting cytochrome (CYP) P450 metabolism, which require LPV dose adjustment (4,28). Introduced as a salvage agent (22), LPV/RTV has become one of the preferred PI choices for first-line regimens in children Ͼ6 months of age in the countries with access to the drug.…”

mentioning

confidence: 99%

Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children

Rakhmanina¹,

Anker

Baghdassarian³

et al. 2009

Antimicrob Agents Chemother

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In adult protease inhibitor (PI)-experienced patients, a lopinavir (LPV) phenotypic inhibitory quotient (PIQ) of >15 has been associated with a higher likelihood of viral suppression. The aims of this study were to develop a population pharmacokinetic (PK) model of LPV in children and to estimate the probability of achieving a PIQ of >15. HIV-infected, PI-experienced children receiving LPV were intensively sampled for 12 h to measure plasma LPV. The data were fitted to candidate PK models (using MM-USCPACK software), and the final model was used to simulate 1,000 children to determine the probability of achieving an LPV PIQ of >15. In 50 patients (4 to 18 years old), the median LPV plasma 12-hour-postdose concentration was 5.9 mg/liter (range, 0.03 to 16.2 mg/liter) lower than that reported in adults. After a delay, LPV was absorbed linearly into a central compartment whose size was dependent on the weight and age of the patient. Elimination was dependent on weight. The regression line of observed versus predicted LPV had an R 2 of 0.99 and a slope of 1.0. Visual predictive checks against all available measured concentrations showed good predictive ability of the model. The probability of achieving an LPV PIQ of >15 was >90% for wild-type virus but <10% for even moderately resistant virus. The currently recommended dose of LPV/ritonavir appears to be adequate for children infected with wild-type virus but is unlikely to provide adequate inhibitory concentrations for even moderately resistant human immunodeficiency virus (HIV). PI-experienced HIV-infected children will likely benefit from longitudinal, repeated LPV measurement in plasma to ensure that drug exposure is most often near the maximal end of the observed safe range.Lopinavir/ritonavir (LPV/RTV) (Kaletra) is the first and only coformulated RTV-boosted protease inhibitor (PI) approved for use in children. The recommended doses for children who weigh more than 15 kg are 10 mg/kg of body weight or 230 mg/m 2 (body surface area) twice daily, with a maximum of 400 mg per dose unless it is combined with drugs affecting cytochrome (CYP) P450 metabolism, which require LPV dose adjustment (4, 28). Introduced as a salvage agent (22), LPV/RTV has become one of the preferred PI choices for first-line regimens in children Ͼ6 months of age in the countries with access to the drug.Despite evidence for good antiviral efficacy among children in a clinical trial setting (16,17,23), the standard dose may not be adequate for every child. Noncompartmental analysis has shown that the average LPV plasma 12-hour-postdose concentration (C trough ) in children given the currently recommended pediatric dose of LPV is 67% lower than in adults (24). Recently, Jullien et al. published a population pharmacokinetics (PK) model of LPV in children aged 0 to 18 years (15). The model was based on a retrospective analysis of LPV plasma measurements in 157 children, with a median of 3 samples (range, 1 to 14) per patient, obtained for monitoring purposes after self-reported LPV intake. In t...

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Safety and Antiviral Response at 12 Months of Lopinavir/Ritonavir Therapy in Human Immunodeficiency Virus-1-Infected Children Experienced With Three Classes of Antiretrovirals

Cited by 19 publications

References 23 publications

Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

Double Boosted Protease Inhibitors, Saquinavir, and Lopinavir/Ritonavir, in Nucleoside Pretreated Children at 48 Weeks

Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children

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