Related Experiment Video
Updated: Mar 13, 2026
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Virological Failure on Long-Acting Injectable Cabotegravir and Rilpivirine: An Analysis of Subtypes, Drug Levels,
Maria Mazzitelli1,2, Milosz Parczewski3, David Burger4
1Dipartimento di Sicurezza e Bioetica-Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
Background:
Virological failure (VF) with long-acting injectable cabotegravir and rilpivirine (CAB/RPV-LA) is uncommon but often associated with selection of resistance, potentially limiting future treatment options. Registration trials associated VF risk with baseline RPV resistance, A1/A6 subtypes, and body mass index (BMI) >30 kg/m2, but these factors have rarely been analyzed in other clinical settings. We summarize the first ∼100 reported VF cases, focusing on subtypes, drug levels, and resistance patterns.
Methods:
Published data on CAB/RPV-LA through July 2025 were analyzed for risk factors. Resistance mutations were interpreted using the Stanford HIVdb database.
Results:
After excluding duplicates, 94 VF cases were analyzed. Only 4.4% met the high-risk threshold of ≥2 risk factors. Subtype A lineages were reported in 26.4%, preexisting RPV mutations in 14.7%, and BMI >30 kg/m2 in 36.9%. At failure, low CAB or RPV levels were observed in 29% but did not differ from treatment successes. Predicted reduced susceptibility to CAB or RPV was observed in 87.2% (56% for both), with CAB resistance mutation N155H more frequently observed among subtype A lineages. Predicted susceptibility to dolutegravir/bictegravir (44.3%), doravirine (39.7%), or etravirine (35.9%) was common, but high-level resistance was rare.
Conclusions:
Emergent resistance in VF cases often resulted in cross-resistance to other nonnucleoside reverse transcriptase inhibitors and integrase strand transfer inhibitors. Although most cases did not meet the high-risk profile as defined by registration trials, subtype A lineages were overrepresented. Low drug levels were not elevated versus treatment successes. These data suggest that subtype-specific factors beyond A6 may influence VF risk and merit further study.
Insights
Virological failure with long-acting injectable cabotegravir/rilpivirine is uncommon. Subtype A lineages, not just high-risk factors, may increase failure risk, warranting further investigation into subtype-specific influences.
Area of Science:
- Infectious Diseases
- Virology
- Pharmacology
Background:
- Virological failure (VF) with long-acting injectable cabotegravir and rilpivirine (CAB/RPV-LA) is rare but can lead to resistance.
- Previous studies linked VF risk to baseline rilpivirine resistance, subtype A1/A6, and high BMI, but these factors need validation in diverse clinical settings.
Purpose of the Study:
- To analyze risk factors, subtypes, drug levels, and resistance patterns in approximately 100 reported cases of virological failure (VF) with CAB/RPV-LA.
Main Methods:
- Analysis of published data on CAB/RPV-LA through July 2025.
- Interpretation of resistance mutations using the Stanford HIVdb database.
Main Results:
- Out of 94 VF cases, only 4.4% met the high-risk threshold of ≥2 factors.
- Subtype A lineages (26.4%), preexisting RPV mutations (14.7%), and BMI >30 kg/m² (36.9%) were observed.
- Reduced susceptibility to CAB/RPV occurred in 87.2%, with N155H common in subtype A lineages. Cross-susceptibility to other antivirals was frequent, but high-level resistance was rare.
Conclusions:
- Emergent resistance often caused cross-resistance to other nonnucleoside reverse transcriptase inhibitors and integrase strand transfer inhibitors.
- Subtype A lineages were overrepresented in VF cases, suggesting subtype-specific factors beyond A6 may influence risk.
- Low drug levels were not elevated in VF cases compared to treatment successes, indicating other factors may be involved.
More Related Videos
Related Concept Videos
01:10Retrovirus Life Cycles
01:29Subviral Agents
02:33Retroviruses