Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

ABSTRACT: OBJECTIVE:We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. DESIGN:CAB long acting is an integrase strand transfer inhibitor formulated as a 200?mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. METHODS:Three groups of rhesus macaques (n?=?8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50?mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50?mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25?mg/kg on week 0 and 50?mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. RESULTS:CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. CONCLUSION:These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

SUBMITTER: Andrews CD 

PROVIDER: S-EPMC5263045 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature