Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251
| Autor: | Amanda Y. Poon, Agegnehu Gettie, Kasi E. Russell-Lodrigue, Natanya Gettie, James F. Blanchard, David D. Ho, Hiroshi Mohri, Zhi Hong, Martin Markowitz, Leslie St. Bernard, William Spreen, Chasity D. Andrews |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Sexual transmission Anti-HIV Agents Pyridones Immunology Simian Acquired Immunodeficiency Syndrome Pharmacology medicine.disease_cause Macaque Injections Intramuscular Virus Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cabotegravir biology.animal medicine Immunology and Allergy Animals 030212 general & internal medicine biology business.industry Infectious dose fungi food and beverages Simian immunodeficiency virus Macaca mulatta Integrase strand transfer inhibitor 030104 developmental biology Infectious Diseases Long acting Treatment Outcome chemistry Delayed-Action Preparations Female Pre-Exposure Prophylaxis business |
| Zdroj: | AIDS (London, England). 31(4) |
| ISSN: | 1473-5571 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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