HIV RNA Screening Reduces Integrase Strand Transfer Inhibitor Resistance Risk in Persons Receiving Long-Acting Cabotegravir for HIV Prevention

Susan H Eshleman; Jessica M Fogel; Elias K Halvas; Estelle Piwowar-Manning; Mark A Marzinke; Ryan Kofron; Zhe Wang; John Mellors; Marybeth McCauley; Alex R Rinehart; Marty St Clair; Adeola Adeyeye; Juan C Hinojosa; Robinson Cabello; Keren Middelkoop; Brett Hanscom; Myron S Cohen; Beatriz Grinsztejn; Raphael J Landovitz; HPTN 083 Study Team

doi:10.1093/infdis/jiac415

HIV RNA Screening Reduces Integrase Strand Transfer Inhibitor Resistance Risk in Persons Receiving Long-Acting Cabotegravir for HIV Prevention

J Infect Dis. 2022 Dec 13;226(12):2170-2180. doi: 10.1093/infdis/jiac415.

Authors

Susan H Eshleman¹, Jessica M Fogel¹, Elias K Halvas², Estelle Piwowar-Manning¹, Mark A Marzinke^{1

3}, Ryan Kofron⁴, Zhe Wang⁵, John Mellors², Marybeth McCauley⁶, Alex R Rinehart⁷, Marty St Clair⁷, Adeola Adeyeye⁸, Juan C Hinojosa⁹, Robinson Cabello¹⁰, Keren Middelkoop¹¹, Brett Hanscom⁵, Myron S Cohen¹², Beatriz Grinsztejn¹³, Raphael J Landovitz¹⁴; HPTN 083 Study Team

Collaborators

HPTN 083 Study Team:
Michael Seisa, Yolanda Lie, William Meyer, Jeanne Marrazzo, Sheila Peel, Carole Wallis, Aida Asmelash, Eric Daar, James Rooney, Richard Clark

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
³ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Medicine, University of California, Los Angeles, California, USA.
⁵ Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁶ FHI 360, Durham, North Carolina, USA.
⁷ ViiV Healthcare, Research Triangle Park, North Carolina, USA.
⁸ Prevention Science Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
⁹ Asociación Civil Selva Amazónica, Iquitos, Peru.
¹⁰ Asociación Via Libre, Lima, Peru.
¹¹ Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
¹² Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
¹³ Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil.
¹⁴ Center for Clinical AIDS Research and Education, University of California, Los Angeles, Los Angeles, California, USA.

Abstract

Background: The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged.

Methods: Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads <500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results.

Results: Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high.

Conclusions: When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP.

Keywords: HIV; HPTN; INSTI; PrEP; cabotegravir; injectable; integrase; prevention; resistance.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Drug Resistance, Viral / genetics
HIV Infections* / drug therapy
HIV Integrase Inhibitors* / pharmacology
HIV Integrase Inhibitors* / therapeutic use
HIV Integrase* / genetics
HIV-1* / genetics
Humans
Mutation
Pyridones / therapeutic use
RNA

Substances

cabotegravir
RNA
Pyridones
HIV Integrase Inhibitors
HIV Integrase

Abstract

Publication types

MeSH terms

Substances

Grants and funding