Predictors of virological failure and time to viral suppression of first line integrase inhibitor based antiretroviral treatment. Clinical Infectious Diseases
Pyngottu et al. aimed to identify risk factors for treatment failure of integrase strand transfer inhibitor (InSTI-) based combined antiretroviral treatment (cART) in drug-naive individuals living with HIV from the Swiss HIV Cohort Study (SHCS) and to assess the impact of minor InSTI resistance-associated mutations (RAMs) on treatment outcome.
The authors studied time-to-treatment failure and time to viral suppression among 1’419 drug-naive patients in the Swiss HIV Cohort Study. In 646 patients with a baseline genotypic resistance test of the integrase, they studied the impact of minor integrase resistance mutations. Virological failure was defined as follows: 2 consecutive RNA values >50 copies/mL after at least 180 days of continuous treatment, 1 value >50 copies/mL after 180 days of treatment followed by treatment change to another drug class, or no viral suppression <50 copies/mL after more than 180 days of treatment.
They observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3–3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1–3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/μL (mHR, 0.5; 95% CI, .3–.8) and >500 cells/ μL (mHR, 0.4; 95% CI, .2–.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6–.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0–1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.
In conclusion, the study shows that response to InSTI-based first-line treatment of drug-naïve patients was excellent. Nevertheless, many of the risk factors commonly associated with therapeutic failure such as the severity of immunodeficiency and stage of the disease were still relevant despite the potency of InSTIs. The chance for virological failure was consistently associated with the baseline viral load and the CD4 count, even in patients on dolutegravir.
Additional comment Dominique Braun and Huldrych Günthard
With this 38th press release in this challenging 2020 due to the COVID-19 pandemic, we say good-bye to you and wish you and your families a Merry Christmas and a Happy New Year. We hope that you will read us again in 2021 and that we can continue to provide you interesting results from the SHCS research community.