To the Editor Long-acting injectable cabotegravir and rilpivirine (CAB-RPV) is approved for people with HIV who have viral suppression with oral antiretroviral therapy (ART), no known or suspected resistance to either drug, and no chronic hepatitis B. In clinical trials, switching to this injectable therapy demonstrated noninferiority to continued oral ART in maintaining viral suppression. The most recent International Antiviral Society–USA (IAS-USA) treatment guidelines1 cited a study of successful treatment with CAB-RPV in 15 people with HIV viremia who were not taking oral ART due to adherence challenges.2 Because of the small size and preliminary nature of this report, CAB-RPV was not recommended in the setting of viremia.
Since publication of the IAS-USA treatment guidelines in December 2022, additional studies of CAB-RPV in people with HIV viremia due to difficulty taking oral ART have been reported. The authors of the original case series have published data on 57 individuals, of whom 94% achieved and maintained viral suppression, with 2 developing treatment failure with resistance.3 The program used intensive case-management services, including community-based supports, case managers and harm reduction services, travel support for visits or blood draws, as well as frequent review of the patients by a dedicated clinical team. In other studies of variable size, duration, and baseline demographic and clinical status, the virologic suppression rates with CAB-RPV in people with HIV viremia ranged from 57% to 100%4,5; however, follow-up for some patients was only a few months. A modeling study6 projected that the benefits of CAB-RPV in people with HIV viremia who could not take oral ART are greatest in those with advanced HIV-related immunosuppression. These accumulating data on using CAB-RPV in people with HIV viremia add to a growing body of evidence that long-acting injectable therapy offers an important treatment option for people with HIV who struggle with oral medication adherence.
Based on these data, and the high risk of disease progression or death in persons with advanced HIV disease who are not taking ART, the IAS-USA panel now makes the following revision to the Guidelines.
When supported by intensive follow-up and case management services, injectable cabotegravir and rilpivirine (CAB-RPV) may be considered for people with viremia who meet the criteria below when no other treatment options are effective due to a patient’s persistent inability to take oral ART (rating AIIa under the conditions described).
Unable to take oral ART consistently despite extensive efforts and clinical support
High risk of HIV disease progression (CD4 cell count <200/μL or history of AIDS-defining complications)
Virus susceptible to both CAB and RPV
If applicable, patients should also be referred for treatment of substance use disorder and/or mental illness.
This change is based on the accumulating evidence cited above. However, no randomized clinical studies exist to support this recommendation, and available data are limited by small numbers with variable follow-up, variation in dosing regimens, and insufficient information regarding the types and intensity of clinical support deployed. To generate more robust data, the panel continues to encourage clinicians to refer eligible patients to prospective clinical trials of this strategy.
Corresponding Author: Paul E. Sax, MD, Brigham and Women’s Hospital, 75 Francis St, Pbb-A-4, Boston, MA 02115 (psax@bwh.harvard.edu).
Published Online: March 1, 2024. doi:10.1001/jama.2024.2985
Conflict of Interest Disclosures: Dr Sax reported receiving grants from Gilead and ViiV; and personal fees from Gilead, Merck, Janssen, and ViiV, outside the submitted work. Dr Thompson reported receiving personal fees for serving as chair of an independent data monitoring committee for Excision Biotherapeutics, outside the submitted work. Dr Saag reported receiving consulting fees from TFF Pharmaceuticals and American Gene Technologies, outside the submitted work.
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