New data out of the United Kingdom offer some reassuring news regarding the clinical impact of non-integrase mutations on HIV treatment outcomes among recently diagnosed people starting integrase inhibitor-based therapy. They also help reinforce recommendations regarding the best ways for us to monitor for, and adjust to, the risk for antiretroviral drug resistance in a range of clinical settings.
Highlighted Study Population and Methods
This study analyzed samples from 1,106 people in the United Kingdom who had recently acquired HIV-1. Recent infection (within six months) was defined using the UK RITA algorithm; RITA excludes those already on treatment at sampling.
Whole-genome sequencing was performed on pre-treatment plasma samples obtained between 2015 and 2021, and these sequences were linked to clinical data. The analysis focused on non-integrase regions and mutations previously implicated in integrase strand transfer inhibitor (INSTI) resistance: Env (Y61H, A539V), Gag-NC (N8S), and 3’ polypurine tract (3’PPT c9053t).
Of the participants, 375 (34%) started an INSTI-based antiretroviral therapy (ART); 337 (90%) were men, median age was33 years, and 196 (52%) had subtype B infection. Median number of viral load (VL) measurements in 24 months after ART start was four. Evaluated endpoints were time to viral suppression and occurrence of viral load blips.
Key Findings
Prevalence of non-integrase mutations:
Env Y61H: 33/375 (≈10%)
Env A539V: 16/375 (5.0%)
3’PPT c9053t: 17/375 (5.0%)
NC N8S: 16/375 (4.8%)
No significant effect of mutations on virological outcomes.
No statistically significant association between these individual non-integrase mutations and time to viral suppression.
No significant associations were found between these mutations and time to viral blip.
Accessory INSTI resistance mutations were found more frequently in viruses that also harbored Env A539V, suggesting potential interactions related to the accumulation of integrase resistance.
Clinical outcomes were good overall.
Read an expert analysis from Benjamin Young, M.D., Ph.D. at TheBodyPro.
Source : TheBodyPro
Get involved
Are you living with HIV/AIDS? Are you part of a community affected by HIV/AIDS and co-infections? Do you work or volunteer in the field? Are you motivated by our cause and interested to support our work?
Subscribe
Stay in the loop and get all the important EATG updates in your inbox with the EATG newsletter. The HIV & co-infections bulletin is your source of handpicked news from the field arriving regularly to your inbox.