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

Kosalaraksa, Pope; Bunupuradah, Torsak; Engchanil, Chulapan; Boonrak, Pitch; Intasan, Jintana; Lumbiganon, Pagakrong; Burger, David M.; Ruxrungtham, Kiat; Schütz, Malte; Ananworanich, Jintanat

doi:10.1097/inf.0b013e31816b4539

Cited by 24 publications

(19 citation statements)

References 20 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pediatric HIV-NAT 017 study which treated children with second-line SQV and LPV/r reported a viral suppression rate similar to that observed in our study with 64% having HIV RNA < 50 copies/ml at week 48 [21]. A non-randomized study in Thai adults showed that the double-boosted PI regimen was not as potent in suppressing HIV RNA to below 50 copies/ml when compared to the single-boosted PI regimen among patients with low grade multi- NRTI resistance mutations [22].…”

Section: Discussionsupporting

confidence: 82%

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

et al. 2012

Self Cite

View full text Add to dashboard Cite

BackgroundLimited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens.MethodsA retrospective chart review was conducted at 8 Thai sites of children who switched to PI –based regimens due to failure of NNRTI –based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks.ResultsData from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002).ConclusionSecond-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.

show abstract

Section: Discussionsupporting

confidence: 82%

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our results showed a similar efficacy compared to the other two available studies of double-boosted PI in experienced HIV-infected children. These two studies assessed the efficacy of the combination of SQV and LPV/r in a cohort of 50 HIV-infected children; the first and the second assessment were performed at week 48 and 96 respectively [13,14]. At week 48 the median CD4 increase was 9% (IQR 5-16) and the percentage of patients with HIV-RNA < 400 and < 50 copies/ml were 78 and 64, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…However, two recent studies showed that dual-boosted SQV and LPV may be an effective and safe alternative for a second-line regimen in pre-treated children, nevertheless a close follow up is necessary because dislipidemia can occur during treatment [13,14]. Therefore, we decided to test this therapeutic option in a long term observational cohort of 7 HIV-infected children.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of a dual boosted protease inhibitor-based regimen, atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric population

et al. 2012

View full text Add to dashboard Cite

BackgroundAlthough dual-boosted protease inhibitors regimen is not recommended in children with HIV infection, such a strategy could be useful in subjects with a complex resistance profile. This study was aimed at assessing the long term efficacy and safety of a double-boosted protease inhibitor combination, fosamprenavir (fAVP) and atazanavir/ritonavir (ATV/r) in a cohort of HIV-infected children and adolescents who had failed with nucleoside reverse transcriptase inhibitors.MethodsSeven vertically infected children and adolescents who had previously failed highly active antiretroviral therapy and were resistant to nucleoside reverse transcriptase inhibitors, received a dual protease inhibitor (PI) regimen including fAVP plus ATV/r for 42 months. The patients were assessed at baseline, every month for the first 24 weeks of therapy and every 3 months until month 32. Physical examination, CD4+ cell count, HIV-RNA viral load, lipid profile and hepatic function were assessed throughout the follow up.ResultsDuring the study no serious adverse events were reported. CD4 absolute number increased over-time in all subjects. At baseline the median HIV-RNA was 6562 cp/mL (ranging 1048 -102772 cp/mL) and rapidly decreased below the limit of detection (50 cp/mL) after 2 months of the new treatment and remained undetectable in all cases through the entire study period. At the beginning of the study all cases showed a normal lipid profile. During the study period, 4/7 subjects showed total cholesterol, low density lipoprotein and triglyceride levels >97th cent.le for the males and 94th cent.le for the females. HDL cholesterol showed protective values. Hepatic enzymes remained stable during the entire observation, whereas total bilirubin showed toxicity II/III grade in 6/7 subjects. No change in fat redistribution and insulin resistance was observed.ConclusionDual-boosted protease inhibitor therapy was virologically and immunologically effective and it could be considered as a possible alternative to a rescue regimen in children and adolescents. However, hypercholesterolemia and hypertriglyceridemia need close follow-up and may limit the use of this therapeutic option.

show abstract

“…In children who failed an NRTI/NNRTI based HAART regimen, a double boosted PI regimen (SQV and LPV/r) was demonstrated to have strong virological and immunological response after 48 weeks and 96 weeks [31,50]. However, as mentioned before, the C min of both PIs were higher than the therapeutic concentrations, resulting in elevated lipids and suggesting further exploration of the possibility of dose reduction of PI in children.…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Abstract: Double boosted SQV/LPV/r resulted in significant CD4 rise and VL decline at 48 weeks. Hyperlipidemia was common. Cmin of both PIs exceeded therapeutic concentrations. Poor adherence caused failure in 10%. No major PI mutations were found.

Cited by 24 publications

References 20 publications

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

Efficacy and safety of a dual boosted protease inhibitor-based regimen, atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric population

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

Contact Info

Product

Resources

About