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

Abstract

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.

First time genotyping of Cryptosporidium spp. isolates from diarrheic stools of Algerian HIV-Infected subjects supports predominant zoonotic transmission routes

“…infection among immunocompromised patient [35,41] and the excellent virological and immunological response with an increased CD4 absolute number over time with the use of double boosted-PI regimen plus 3TC as second-line treatment [42], in the current study, patients were not able to clear off the infection, and their CD4 counts remained below 200 cells/ mm3 which aligns with previous studies [43,44].…”

Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens

“…The virology analyses presented here from the APV29005 and APV20002 studies together encompass the widest age range (4 weeks to 18 year age), and the largest number of FPV and FPV/RTV-treated pediatric patients from prospective clinical trials published to date. The overall findings from the APV29005 and APV20002 studies of low rates of VF and low rates of selection for PI mutations at VF and FPV RS, especially in the FPV/RTV treated populations, are similar to the limited data available for two small pediatric studies with FPV/RTV, where low rates of VF and selection for resistance mutations were observed [ 6 , 7 ]. In one, 7 ART-experienced, HIV-infected children whose virus already contained NRTI resistance mutations were switched to dual protease therapy with FPV/RTV and ATV.…”

“…In one, 7 ART-experienced, HIV-infected children whose virus already contained NRTI resistance mutations were switched to dual protease therapy with FPV/RTV and ATV. All 7 children became virologically suppressed shortly after therapy initiation and remained suppressed to <50 copies/mL through 42 months on therapy [ 6 ]. In a second study, HIV-infected, ART-naïve and ART-experienced children were treated with FPV/RTV (19/20) or FPV-containing regimens (1/20), and 14/20 (70%) children achieved or maintained virologic suppression.…”

“…Although the only other prior FPV/RTV pediatric studies have already been described [ 6 , 7 ], 2 additional pediatric studies that include resistance evaluations in second-line treatment regimens with other PIs are available for comparison [ 13 , 14 ]. In one, 30% of ART-experienced children switched to a darunavir/ritonavir-based regimen aged 6-17 years experienced VF (<1 log 10 HIV-1 RNA reduction) through 48 weeks.…”

“…While the FPV resistance profile is well documented in HIV-infected adults, there have been few previous pediatric studies utilizing FPV-based regimens and these have had with very limited resistance data [ 6 , 7 ]. When HIV-infected children experience VF while receiving FPV-containing ART regimens as first or second line or salvage therapy, it is vital to know if the FPV resistance-associated mutations that can be selected will be the same as those seen in the more frequently studied adult population and whether these mutations result in cross resistance to other PIs and thus impact future drug sequencing options.…”