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.
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.
Authors: William Spreen; Susan L Ford; Shuguang Chen; David Wilfret; David Margolis; Elizabeth Gould; Stephen Piscitelli Journal: J Acquir Immune Defic Syndr Date: 2014-12-15 Impact factor: 3.731
Authors: Chasity D Andrews; Yun Lan Yueh; William R Spreen; Leslie St Bernard; Mar Boente-Carrera; Kristina Rodriguez; Agegnehu Gettie; Kasi Russell-Lodrigue; James Blanchard; Susan Ford; Hiroshi Mohri; Cecilia Cheng-Mayer; Zhi Hong; David D Ho; Martin Markowitz Journal: Sci Transl Med Date: 2015-01-14 Impact factor: 17.956
Authors: Michael C Thigpen; Poloko M Kebaabetswe; Lynn A Paxton; Dawn K Smith; Charles E Rose; Tebogo M Segolodi; Faith L Henderson; Sonal R Pathak; Fatma A Soud; Kata L Chillag; Rodreck Mutanhaurwa; Lovemore Ian Chirwa; Michael Kasonde; Daniel Abebe; Evans Buliva; Roman J Gvetadze; Sandra Johnson; Thom Sukalac; Vasavi T Thomas; Clyde Hart; Jeffrey A Johnson; C Kevin Malotte; Craig W Hendrix; John T Brooks Journal: N Engl J Med Date: 2012-07-11 Impact factor: 91.245
Authors: Jared M Baeten; Deborah Donnell; Patrick Ndase; Nelly R Mugo; James D Campbell; Jonathan Wangisi; Jordan W Tappero; Elizabeth A Bukusi; Craig R Cohen; Elly Katabira; Allan Ronald; Elioda Tumwesigye; Edwin Were; Kenneth H Fife; James Kiarie; Carey Farquhar; Grace John-Stewart; Aloysious Kakia; Josephine Odoyo; Akasiima Mucunguzi; Edith Nakku-Joloba; Rogers Twesigye; Kenneth Ngure; Cosmas Apaka; Harrison Tamooh; Fridah Gabona; Andrew Mujugira; Dana Panteleeff; Katherine K Thomas; Lara Kidoguchi; Meighan Krows; Jennifer Revall; Susan Morrison; Harald Haugen; Mira Emmanuel-Ogier; Lisa Ondrejcek; Robert W Coombs; Lisa Frenkel; Craig Hendrix; Namandjé N Bumpus; David Bangsberg; Jessica E Haberer; Wendy S Stevens; Jairam R Lingappa; Connie Celum Journal: N Engl J Med Date: 2012-07-11 Impact factor: 91.245
Authors: David A Margolis; Cynthia C Brinson; Graham H R Smith; Jerome de Vente; Debbie P Hagins; Joseph J Eron; Sandy K Griffith; Marty H St Clair; Marita C Stevens; Peter E Williams; Susan L Ford; Britt S Stancil; Melinda M Bomar; Krischan J Hudson; Kimberly Y Smith; William R Spreen Journal: Lancet Infect Dis Date: 2015-07-19 Impact factor: 25.071
Authors: Jeanne M Marrazzo; Gita Ramjee; Barbra A Richardson; Kailazarid Gomez; Nyaradzo Mgodi; Gonasagrie Nair; Thesla Palanee; Clemensia Nakabiito; Ariane van der Straten; Lisa Noguchi; Craig W Hendrix; James Y Dai; Shayhana Ganesh; Baningi Mkhize; Marthinette Taljaard; Urvi M Parikh; Jeanna Piper; Benoît Mâsse; Cynthia Grossman; James Rooney; Jill L Schwartz; Heather Watts; Mark A Marzinke; Sharon L Hillier; Ian M McGowan; Z Mike Chirenje Journal: N Engl J Med Date: 2015-02-05 Impact factor: 91.245
Authors: Chasity D Andrews; William R Spreen; Hiroshi Mohri; Lee Moss; Susan Ford; Agegnehu Gettie; Kasi Russell-Lodrigue; Rudolf P Bohm; Cecilia Cheng-Mayer; Zhi Hong; Martin Markowitz; David D Ho Journal: Science Date: 2014-03-04 Impact factor: 47.728
Authors: Joseph S Redman; J Nicholas Francis; Robert Marquardt; Damon Papac; Alan L Mueller; Debra M Eckert; Brett D Welch; Michael S Kay Journal: Mol Pharm Date: 2018-02-22 Impact factor: 4.939
Authors: Raphael J Landovitz; Deborah Donnell; Meredith E Clement; Brett Hanscom; Leslie Cottle; Lara Coelho; Robinson Cabello; Suwat Chariyalertsak; Eileen F Dunne; Ian Frank; Jorge A Gallardo-Cartagena; Aditya H Gaur; Pedro Gonzales; Ha V Tran; Juan C Hinojosa; Esper G Kallas; Colleen F Kelley; Marcelo H Losso; J Valdez Madruga; Keren Middelkoop; Nittaya Phanuphak; Breno Santos; Omar Sued; Javier Valencia Huamaní; Edgar T Overton; Shobha Swaminathan; Carlos Del Rio; Roy M Gulick; Paul Richardson; Philip Sullivan; Estelle Piwowar-Manning; Mark Marzinke; Craig Hendrix; Maoji Li; Zhe Wang; Jeanne Marrazzo; Eric Daar; Aida Asmelash; Todd T Brown; Peter Anderson; Susan H Eshleman; Marcus Bryan; Cheryl Blanchette; Jonathan Lucas; Christina Psaros; Steven Safren; Jeremy Sugarman; Hyman Scott; Joseph J Eron; Sheldon D Fields; Nirupama D Sista; Kailazarid Gomez-Feliciano; Andrea Jennings; Ryan M Kofron; Timothy H Holtz; Katherine Shin; James F Rooney; Kimberly Y Smith; William Spreen; David Margolis; Alex Rinehart; Adeola Adeyeye; Myron S Cohen; Marybeth McCauley; Beatriz Grinsztejn Journal: N Engl J Med Date: 2021-08-12 Impact factor: 176.079
Authors: Angela R Bazzi; Chad J Valasek; Samantha A Streuli; Carlos F Vera; Alicia Harvey-Vera; Morgan M Philbin; Katie B Biello; Alexis M Roth; Steffanie A Strathdee; Heather A Pines Journal: AIDS Patient Care STDS Date: 2022-06-21 Impact factor: 5.944
Authors: Philip L Tzou; Diane Descamps; Soo-Yon Rhee; Dana N Raugi; Charlotte Charpentier; Nuno Taveira; Robert A Smith; Vicente Soriano; Carmen de Mendoza; Susan P Holmes; Geoffrey S Gottlieb; Robert W Shafer Journal: J Infect Dis Date: 2020-06-11 Impact factor: 5.226
Authors: Robert A Smith; Vincent H Wu; Christopher G Zavala; Dana N Raugi; Selly Ba; Moussa Seydi; Geoffrey S Gottlieb Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Raphael J Landovitz; Sue Li; Beatriz Grinsztejn; Halima Dawood; Albert Y Liu; Manya Magnus; Mina C Hosseinipour; Ravindre Panchia; Leslie Cottle; Gordon Chau; Paul Richardson; Mark A Marzinke; Craig W Hendrix; Susan H Eshleman; Yinfeng Zhang; Elizabeth Tolley; Jeremy Sugarman; Ryan Kofron; Adeola Adeyeye; David Burns; Alex R Rinehart; David Margolis; William R Spreen; Myron S Cohen; Marybeth McCauley; Joseph J Eron Journal: PLoS Med Date: 2018-11-08 Impact factor: 11.069