Fosamprenavir calcium plus ritonavir for HIV infection

Abstract

Fosamprenavir is a protease inhibitor (PI) approved for the treatment of HIV-1 infection. Fosamprenavir is a prodrug of amprenavir developed to reduce the pill burden yet maintain the unique resistance pattern and efficacy associated with amprenavir. In a head-to-head, noninferiority trial in antiretroviral treatment-naive HIV-infected patients, the antiviral efficacy and tolerability of ritonavir-boosted fosamprenavir was not inferior to ritonavir-boosted lopinavir, when the PIs were combined with two other nucleoside reverse transcriptase inhibitors. There are fewer studies published about fosamprenavir use in antiretroviral treatment-experienced HIV-infected patients. The high genetic barrier to the development of resistance to fosamprenavir and the low level of cross-resistance between ritonavir-boosted fosamprenavir and other PI regimens are notable. As with amprenavir, gastrointestinal disturbance and rash are the most frequent short-term treatment-limiting events with fosamprenavir. Treatment with ritonavir-boosted fosamprenavir can produce a durable response. To date, fosamprenavir is one of the recommended preferred PI components for the treatment of antiretroviral-naive HIV-infected patients.

Post‐licensing safety of fosamprenavir in HIV‐infected children in Europe

“…However, the number and rate of grade ≥3 events were low, with no discernible trend by duration of exposure. There were an elevated number of grade 2 hypercholesterolemia events, and increased serum cholesterol has previously been described in patients treated with protease inhibitors . No serious clinical AEs related to FPV/r were reported.…”

Current and Novel Inhibitors of HIV Protease

“…Several mutations, namely V32I, I47V/A, I50V, I54L/M, L76V and I84 V/A, are relative contraindications to the use of FPV. The side effects of FPV are comparable to those of APV [52]. …”

Pharmacokinetics and 48-week Safety and Antiviral Activity of Fosamprenavir-containing Regimens in HIV-infected 2- to 18-year-old Children

“…13,18 Vomiting was more common in children in the FPV group, perhaps due to the larger volumes of FPV suspension or the younger age of this cohort. Grade 3/4 neutropenia was reported in 15% of children, although the late onset and the use of concomitant medications that may be associated with neutropenia suggest that it is unlikely to be FPV related.…”

“…The proportion of subjects achieving HIV-1 RNA <400 copies/mL at week 48 ranged from 48% among PI-experienced to 83% among ART-naïve children; this compares to 66% to 73% in ART-naïve adults in the NEAT, SOLO and KLEAN studies and 58% in ART-experienced adults in the CONTEXT study indicating an adequate antiviral response when considering that this pediatric population included PI-naïve and PI-experienced subjects. 18,19 …”