icon-folder.gif   Conference Reports for NATAP  
  18th International Workshop on
Clinical Pharmacology of Antiviral Therapy
June 14-17, 2017
Chicago, Ill.C
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Effect of a high fat meal on the pharmacokinetics of the HIV integrase inhibitor, cabotegravir
  Reported by Jules Levin
18th International Workshop on Clinical Pharmacology of Antiviral Therapy; June 14-16, 2017; Chicago, IL
What is Cabotegravir - for HIV treatment & prevention
Two forms of cabotegravir are being studied: tablets that are taken by mouth (known as oral cabotegravir or oral CAB) and a long-acting injectable form that is injected into the muscle (known as cabotegravir LA or CAB LA; LA stands for "long-acting").6,7 (A long-acting drug formulation works over a long period of time. Using this type of drug might mean that the drug could be taken less often, making a treatment or prevention regimen simpler to take.)4
Cabotegravir is an investigational integrase strand transfer inhibitor (INSTI) and is not approved by regulatory authorities anywhere in the world. Cabotegravir is being developed by ViiV Healthcare for the treatment and prevention of HIV and is currently being evaluated as a long-acting, nanosuspension formulation for intramuscular injection and also as a once-daily oral tablet for induction prior to long-acting injection.
Expected times for FDA submission: for treatment Flair & Atlas based on current recruitment some time in first half of 2019; for Prevention/PrEP hard to predict but likely a couple of years after treatment is submitted to FDA.
Phase 3 
The HPTN083 study is in MSM and trans gender women, that trial has started recruitment and aims to enroll 4500 subjects.  The HPTN084 study will enroll women and will take place in sub-Saharan Africa and is due to start later this year and will enroll 3200 subjects.  Both trials are International and fully recruited and now just need to accrue time on therapy before we can do the analysis of the data. 
......In FLAIR, treatment-naïve patients will be given a 20-week daily oral dolutegravir/abacavir/lamivudine (Triumeq®) regimen, and will then be randomised to switch to a regimen of long-acting, injectable cabotegravir and rilpivirine, or remain on oral therapy.[2] In ATLAS, treatment-experienced patients with suppressed viral load will be randomised to switch from their existing antiretroviral therapy (ART) to long-acting, injectable formulations of cabotegravir and rilpivirine or remain on oral ART.[3] Participants will be enrolled from investigative sites across Africa, the Americas, Asia and Europe.
HPTN 084 will test the safety and efficacy of injectable cabotegravir for HIV prevention in young women in sub-Saharan Africa beginning in 2017. This study will be supported by NIAID, the U.S. Agency for International Development and ViiV Healthcare.
NIAID is sponsoring the study, called HPTN 083, and ViiV Healthcare and Gilead Sciences are providing the study medications. The study will enroll 4,500 men who have sex with men and transgender women who have sex with men at 45 sites in eight countries in the Americas, Asia and Africa. Participants will be aged 18 years or older and at high risk for HIV infection. Results are expected in 2021. HPTN 083 study participants will be randomly assigned to either the cabotegravir group or the Truvada group. Neither the participants nor the study team will know who is in which group until the end of the trial. "The HPTN 083 study has the potential to provide game changing data as the first large-scale test of a long-acting injectable drug for HIV prevention," said Protocol Co-Chair Beatriz Grinsztejn, M.D., Ph.D. Dr. Grinsztejn directs the Instituto de Pesquisa Clinica Evandro Chagas HIV/AIDS Clinical Research Centre of the Oswaldo Cruz Foundation-Fiocruz in Rio de Janeiro, Brazil. https://www.niaid.nih.gov/news-events/nih-launches-first-large-trial-long-acting-injectable-drug-hiv-prevention
HPTN 084
A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women. HPTN 084 is a study being done to to evaluate the safety and efficacy of the injectable agent, cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis (PrEP) in HIV-uninfected women. HPTN 084 will enroll approximately 3,200 women 18 to 45 years old in sub-Saharan Africa who are at risk for acquiring HIV. https://www.hptn.org/research/studies/hptn084
  HPTN 083 [MSM, transgender women] & HPTN 084 [for women]
https://www.niaid.nih.gov/news-events/nih-launches-first-large-trial-long-acting-injectable-drug-hiv-prevention A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), for Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women who have Sex with Men..... https://www.hptn.org/sites/default/files/2016-06/(T5) Raphael Landovitz - FINAL v2 (6.14.2016)_0.pdf
CROI: Long-term Safety and Efficacy of CAB and RPV as 2-Drug Oral Maintenance Therapy - (02/18/17) 
CROI: ECLAIR: Phase 2A Safety and PK Study of Cabotegravir LA in HIV-Uninfected Men.......Long-Acting Cabotegravir Data Suggest PrEP Injections Every 8 Week -  (02/24/16) IAC: Cabotegravir + Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 48 Results - (07/25/16)
 IAC: Satisfaction, Tolerability, and Acceptability of Cabotegravir (CAB) + Rilpivirine (RPV) Long-Acting Therapy: LATTE-2 Results - (07/29/16)
IAC: Experiences with long acting injectable ART: a qualitative study among PLHIV participating in a Phase II study of Cabotegravir + Rilpivirine (LATTE-2) in the United States and Spain - (07/25/14)
IAC: Persistence of Rilpivirine Following Single Dose of Long-Acting Injection - (07/29/16)
new PrEP for women........CROI: GSK1265744 Long-Acting Protects Macaques against Repeated High-Dose Intravaginal Challenges & Depo Provera-treated - (03/14/14)
PrEP for MSM.....CROI: Long-Acting Integrase Inhibitor GSK744 for PrEP (Once Monthly or maybe longer) - (03/05/14)......."GSK744 LA has afforded high---level protection against repeated intrarectal SHIV challenges in rhesus macaques......plasma concentrations >3X PAIC90 result in 100% protection.....plasma levels corresponding to protection can be readily achieved in man with quarterly 800mg intramuscular injections.......These data support moving GSK744 LA into clinical evaluation as PrEP in high-risk men who have sex with men - Phase 2 safety and tolerability studies commence in Spring 2014 
Effect of a high fat meal on the pharmacokinetics of the HIV integrase inhibitor, cabotegravir
Reported by Jules Levin
18th International Workshop on Clinical Pharmacology of Antiviral Therapy; June 14-16, 2017; Chicago, IL
Patel P1, Ford S2, Lou Y2, Bakshi K3, Tenorio A1, Zhang Z2, Pan R3, Speen W1 1ViiV Healthcare, Research Triangle Park, United States; 2PAREXEL International, Durham, United States; 3GlaxoSmithKline, Collegeville, United States