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

Abstract

BACKGROUND:

Although 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.

METHODS:

Seven 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.

RESULTS:

During 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.

CONCLUSION:

Dual-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.

• Authors: Stefano Rusconi, Vania Giacomet, Chiara Mameli, Alessandra Viganò, Ottavia Viganò, Fulvio Adorni, Massimo Galli, Gian Vincenzo Zuccotti
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 12 Pg. 179 (Aug 06 2012) ISSN: 1471-2334 [Electronic] England
• PMID: 22866946 (Publication Type: Journal Article)

Chemical References

• Anti-HIV Agents
• Carbamates
• Furans
• HIV Protease Inhibitors
• Lipids
• Oligopeptides
• Organophosphates
• Pyridines
• RNA, Viral
• Sulfonamides
• Atazanavir Sulfate
• Ritonavir
• fosamprenavir

Topics

• Adolescent
• Anti-HIV Agents (administration & dosage)
• Antiretroviral Therapy, Highly Active (methods)
• Atazanavir Sulfate
• CD4 Lymphocyte Count
• Carbamates (administration & dosage)
• Child
• Female
• Furans
• HIV Infections (drug therapy)
• HIV Protease Inhibitors (administration & dosage)
• Humans
• Lipids (blood)
• Male
• Oligopeptides (administration & dosage)
• Organophosphates (administration & dosage)
• Pyridines (administration & dosage)
• RNA, Viral (blood)
• Ritonavir (administration & dosage)
• Salvage Therapy (methods)
• Sulfonamides (administration & dosage)
• Treatment Outcome
• Viral Load