Virologic Risk Factors for Cabotegravir Plus Rilpivirine Failure in Treatment-Naive HIV

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Investigators sought to identify factors associated with the risk of virologic failure for cabotegravir plus rilpivirine in treatment-naive patients with HIV.

Among patients with HIV who were treatment naive, 10.1% were ineligible for cabotegravir plus rilpivirine dual therapy due to the prevalence of rilpivirine resistance-associated mutations (RAMs) and HIV-1 subtype A6/A1 sequences, according to study results from 3 large genotypic databases published in the Journal of Antimicrobial Chemotherapy. The findings highlighted the need to check for genotypic resistance profiles and viral subtypes in patients with HIV before initiating cabotegravir plus rilpivirine therapy.

Between 2010 and 2020, researchers analyzed 4212 reverse transcriptase and integrase sequences from treatment-naive patients from 3 databases in Paris, France. Among the 4212 sequences, 38.6% (n=1627) belonged to subtype B, 32.4% (n=1363) belonged to CRF02 AG, and 5.1% (n=214) belonged to subtype A with 183 being subtype A6/A1.

When taking into account the L74I polymorphism, the prevalence of cabotegravir RAMs was 16.2% and was higher in non-B subtypes compared with B subtype (21.5% vs 7.7%; P <.0001). However, resistance to cabotegravir was very low among patients (0.74%; n=31), according to the National Agency for AIDS Research (ANRS) algorithm for resistance interpretation.

The prevalence of rilpivirine RAMs was 14.3% with no difference between non-B subtypes and the B subtype (P =.6). Unlike resistance interpretation for cabotegravir, 6.2% (n=261) of patients exhibited viruses resistant to rilpivirine. Of the 261 patients, 17 had HIV-1 subtype A6/A1 sequences.

Cabotegravir and rilpivirine RAMs were mainly represented by the presence of the L74I polymorphism in integrase (13.0%; n=547) and E138A polymorphisms in reverse transcriptase (3.2%; n=134) and were stable over the decade. Prevalence was higher in non-B subtypes compared with the B subtype for both polymorphisms (P <.0001 for L74I and P =.0003 for E138A). However, the presence of both polymorphisms was rare and detected in only 16 (0.4%) patients.

Thus, when combining HIV-1 subtype A6/A1 prevalence (4.3%; n=183) and rilpivirine RAMs (5.8%; n=244), 10.1% of patients would be ineligible for cabotegravir plus rilpivirine dual therapy due to baseline virologic risk factors.

The investigators emphasized “the need for a pre-therapeutic genotypic resistance test to detect polymorphisms and transmitted drug resistance and to define HIV-1 subtype,” so that risk of virologic failure and emergence of resistance is minimized.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Charpentier C, Storto A, Soulié C, et al. Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients. J Antimicrob Chemother. Published online May 20, 2021. doi:10.1093/jac/dkab161