Patients who experience a viral rebound during treatment with the injectable combination of cabotegravir and rilpivirine (CAB/RPV) may face limited options for further therapy. The reason is the development of drug resistance, which complicates not only the continued use of these agents but also other drugs from the same classes. The findings were presented at the 20th European AIDS Conference in Paris.
Although such cases remain rare, researchers warn that the consequences can be serious. The CAB/RPV combination is considered an effective long-acting injectable therapy that replaces daily oral treatment. However, in cases of treatment failure, the virus may develop mutations that reduce susceptibility to integrase inhibitors (INIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).
A study led by Maria Mazzitelli of the Catholic University of Rome identified 94 cases of virologic failure, representing about 1.3% of all individuals receiving CAB/RPV. More than half of these patients developed resistance to both components of the regimen. Some also showed reduced sensitivity to other commonly used drugs — dolutegravir, bictegravir, etravirine, and doravirine.
The French Dat’AIDS cohort, which included more than 2,000 participants, showed a similar proportion of viral rebounds — 1.3%. In several cases, mutations were detected that made further use of INIs impossible.
A review of seven clinical trials confirmed that the overall risk of virologic failure with CAB/RPV is comparable to that of three-drug oral therapy, but the risk of developing resistance to integrase inhibitors is five times higher.
Experts emphasize that such cases require close clinical monitoring. Patients with high body mass index, specific viral subtypes, or pre-existing mutations are advised to regularly monitor drug levels and viral load. In the event of treatment failure, it is essential to promptly select an alternative regimen to prevent the further spread of resistant virus strains.