Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children

Puthanakit, Thanyawee; Bunupuradah, Torsak; Ananworanich, Jintanat; Gorowara, Meena; Phasomsap, Chayapa; Jupimai, Thidarat; Boonrak, Pitch; Pancharoen, Chitsanu; Burger, David M.; Ruxrungtham, Kiat

doi:10.1093/jac/dkp322

Cited by 21 publications

(20 citation statements)

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“…The effectiveness of the PI‐based ART regimens in our cohort is comparable to that of other previous studies . Puthanakit et al .…”

Section: Discussionsupporting

confidence: 89%

“…Puthanakit et al . found that, at week 48 of treatment with PI‐based regimens, the median CD4 percentage was significantly increased in both groups of children who received the standard and low‐dose regimens. Kosalaraksa et al .…”

Section: Discussionmentioning

confidence: 91%

“…Puthanakit et al . conducted a study among 24 HIV‐infected Thai children (median age 9.5 years) who failed first‐line ART (dual NRTI‐based and NNRTI‐based regimens) using two doses of LPV/RTV as the PI‐based regimen [a WHO‐recommended dose and a low dose (70% of the standard dose)]. They found that the overall viral suppression rate (< 50 copies/mL) was 67%.…”

Section: Discussionmentioning

confidence: 99%

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Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment

2012

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ObjectivesVirological failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens has become a problem in HIV-infected children on long-term antiretroviral therapy (ART). Protease inhibitor (PI)-based regimens are therefore often given to children failing NNRTI-based regimens. The aim of the study was to assess the 48-week effectiveness, safety and predictive factors for viral suppression of PI-based regimens in HIV-infected Thai children who had failed NNRTI-based regimens. MethodsThis study assessed 41 HIV-infected children who had failed first-line NNRTI-based regimens and were switched to PI-based regimens for at least 48 weeks. We assessed their CD4 cell counts, plasma HIV RNA levels, weight-for-age and height-for-age z-scores, and adverse events. ResultsThe children's median age was 9.5 years (range 1.5-15.8 years). At baseline, their median CD4 cell count was 276 cells/mL [interquartile range (IQR) 160-749 cells/mL], and their median plasma HIV RNA level was 4.5 log10 HIV-1 RNA copies/mL (IQR 3.9-4.8 log10 copies/mL). After 48 weeks of PI-based therapy, their CD4 cell counts increased to a median of 572 cells/mL (IQR 343-845 cells/mL) and in 73.2% plasma HIV RNA levels decreased to < 50 copies/mL. Their median weight-for-age and height-for-age z-scores were stable over the period of the study. Diarrhoea occurred in 29.3% of patients. Triglyceride levels were significantly higher at weeks 24 and 48 in comparison to baseline measurements. ConclusionsPI-based regimens are safe and effective for HIV-infected Thai children who have failed first-line NNRTI-based regimens. However, long-term follow-up is warranted in order to ascertain the feasibility and sustainability of these new regimens. Keywords: HIV-infected children, effectiveness, PI-based regimens Accepted 18 September 2012 IntroductionAccording to global estimates, in 2009 about 2.5 (1.7-3.4) million children under the age of 15 years were living with HIV infection [1], and at the end of 2009, about 356 400 of these children were receiving antiretroviral therapy (ART) [2]. The use of ART for the treatment of HIV infection in children has greatly changed the course of the disease, increasing survival rates and improving quality of life [3][4][5]. Children living with HIV are now surviving through adolescence into adult life, which creates new challenges in terms of adherence to treatment regimens, drug resistance and pill burdens. With expanding access to ART, many are experiencing treatment failures requiring second-line regimens [6][7][8] DOI: 10.1111/j.1468-1293.01061.x © 2012 British HIV Association HIV Medicine (2013 ORIGINAL RESEARCH 226In 2008, 10% of Asian and 3.3% of African HIV-infected children were on second-line ART [9]. The recommended second-line regimen for children who fail first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART is boosted protease inhibitors (PIs) with nucleoside reverse transcriptase inhibitors (NRTIs). World Health Organization (WHO) treatment guidelines...

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“…The effectiveness of the PI‐based ART regimens in our cohort is comparable to that of other previous studies . Puthanakit et al .…”

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment

2012

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“…This rate is comparable to a previously reported 67% virologic suppression rate in Thai children using second-line lopinavir/ritronavir-based HAART (24). The PENPACT-1 study in US and European children reported a 7% virologic failure rate in children on PI-based second-line (25).…”

Section: Discussionsupporting

confidence: 85%

Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

et al. 2013

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Background The WHO recommends boosted protease inhibitor (bPI)-based highly active antiretroviral therapy (HAART) after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. Methods Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥24 weeks of NNRTI-based HAART followed by ≥24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virologic suppression (HIV-RNA <400 copies/ml) and immune recovery (CD4% ≥25% if age <5 years and CD4 count ≥500 cells/mm3 if age ≥5 years) at 48 and 96 weeks. Results Of 3422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was −1.9 (n=121), CD4% was 12.5% (n=106), CD4 count was 237 (n=112) cells/mm3, and HIV-RNA was 4.6 log10copies/ml (n=61). The most common PI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV-RNA and 73% (58/79) had fasting triglycerides ≥130mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) virologic suppression, and hypertriglyceridemia occurred in 66% (33/50). Predictors for virologic suppression at week 48 were longer duration of NNRTI-based HAART (p=0.006), younger age (p=0.007), higher WAZ (p=0.020), and HIV-RNA at switch <10,000 copies/ml (p=0.049). Conclusion In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by one year, and two-thirds had hyperlipidemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

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“…A lower dose of LPV/r at 266/66 mg twice daily used together with SQV displayed adequate LPV PK parameters in adults [49]. Similarly in a pediatric study, Thai HIV-infected, PI-naïve children were treated with either the WHO recommended dose of LPV/r or 70% of the standard dose, with 2 NRTI backbone [53]. The PK parameters of LPV and RTV were not significantly different in both groups, and after 48 weeks the safety and efficacy were excellent.…”

Section: Introductionmentioning

confidence: 99%

Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings

Ramautarsing

Ananworanich

2010

AIDS Res Ther

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Although access to antiretroviral therapy (ART) for the treatment of HIV has increased during the last decade, many patients are still in need of treatment. With limited funds to provide ART to millions of patients worldwide, there is a need for alternative ways to scale up ART in resource limited settings. This review provides an overview of pharmacokinetic, safety and efficacy studies of generic and reduced dose ART. The production of generic ART has greatly influenced the decline in drug prices and the increased in ART access. Generic ART has good pharmacokinetic profile, safety and efficacy. Toxicity is however the main cause for ART discontinuation. Several dose reduction studies have shown adequate pharmacokinetic parameters and short term efficacy with reduced dose ART. Ethnicity may affect drug metabolism; several pharmacokinetic studies have confirmed higher plasma ART concentration in Asians. Randomized efficacy trial of reduced versus standard ART is warranted.

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Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children

Abstract: Low-dose lopinavir displayed adequate pharmacokinetic parameters and good efficacy as compared with standard-dose lopinavir in Thai children. A larger study to investigate the efficacy of low-dose lopinavir is warranted.

Cited by 21 publications

References 21 publications

Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment

Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment

Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings

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