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Updated: Jul 15, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Outcomes for persons with triple-class resistant HIV and a history of virologic failure
Suzanne M Ingle1, Fabrice Bonnet2, Linda Wittkop3
1Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Objective:
To assess outcomes of heavily treatment experienced people with HIV (PWH) who received the antiretroviral therapy salvage regimen containing raltegravir, etravirine, and darunavir/ritonavir (known as TRIO).
Methods:
Data were from the ART Cohort Collaboration, which is a collaboration of European and North American HIV cohort studies. Adult PWH were eligible if they had a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors; three or more primary protease inhibitor and nucleoside reverse transcriptase inhibitor mutations; three or fewer darunavir and nonnucleoside reverse-transcriptase inhibitor mutations; received TRIO between 2007 and 2018; virologic failure at TRIO start; and did not receive any TRIO drugs previously. Follow-up began at TRIO start. We examined rates of virologic suppression on TRIO, AIDS/death, receipt of drug-reducing regimens post-TRIO in those virologically suppressed, and subsequent virologic response. We used a competing risks framework to estimate 5-y cumulative incidence of outcomes.
Results:
Among 126 eligible PWH, 24% were female, and median age was 46 y (IQR: 41-50). Median follow-up was 7.9 y (IQR: 5.1-9.3). A total of 94 (74.6%) were virologically suppressed on TRIO. Of these, 26 (28%) subsequently switched to a drug-reducing regimen, of whom 19 of 26 (73.1%) were virologically suppressed at their next viral load measure. The 5-y cumulative incidence of outcomes was stop TRIO and start another three or more drug regimen (39.1%); simplify (16.0%); stop TRIO without switching (8.8%); and death on TRIO (7.2%).
Conclusions:
Although the most common outcome after TRIO was switch to another three or more drug regimen, almost one third of virologically suppressed PWH under TRIO (with a history of multidrug resistance) switched to a drug-reducing regimen, the majority of whom maintained suppression.
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