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Review
. 2022 Oct;19(5):384-393.
doi: 10.1007/s11904-022-00616-y. Epub 2022 Sep 16.

Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?

Urvi M Parikh  1 , Catherine A Koss  2 , John W Mellors  3
Affiliations
Review

Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?

Urvi M Parikh et al. Curr HIV/AIDS Rep. 2022 Oct.

Abstract

Purpose of review: Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation.

Recent findings: The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention.

Keywords: Cabotegravir; HIV drug resistance; HIV prevention; Integrase strand transfer inhibitors (INSTI); Pre-exposure prophylaxis.

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Conflict of interest statement

U.M.P. reports consulting agreements from Merck, outside the submitted work. C.A.K has received grant support to the University of California, San Francisco from the Gilead Research Scholars Program in HIV. J.W.M. reports consulting agreements from Gilead Sciences, Inc., and Infectious Disease Connect, and shares/share options from Infectious Disease Connect and Abound Bio, outside the submitted work.

Figures

Fig. 1
Fig. 1
Causes and potential consequences of cabotegravir resistance for HIV prevention and treatment
See this image and copyright information in PMC

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