Risk of Mortality Similar Between Most First-Line Antiretroviral Regimens for HIV

Role of Highly-Active Antiretroviral Therapy
Role of Highly-Active Antiretroviral Therapy
Researchers compared mortality outcomes among patients with HIV infection receiving integrase strand transfer inhibitor-based antiretroviral therapy (ART) compared with those receiving other ART regimens.

Mortality rates did not significantly differ between most first-line antiretroviral therapy (ART) regimens for the treatment of HIV infection, according to results of a study published in The Lancet HIV.

In recent years, ART regimens among patients with HIV infection have commonly included integrase strand transfer inhibitors (INSTIs). Owing to the lack of data on mortality risk among receiving INSTI-based ART, researchers compared the risk for all-cause mortality among patients who received INSTI-based ART vs those who received other types of ART regimens between 2013 and 2018. The analysis included only patients whose ART regimens comprised 3 or more medications.

Data for this analysis were obtained from the Antiretroviral Therapy Cohort Collaboration and UK Collaborative HIV Cohort. Assessed ART treatments included rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, and efavirenz.

Overall, 62,500 patients were included in the analysis, of whom the median age was 28 (IQR, 30-48) years, 19.9% were women, and 21.2% were receiving dolutegravir-based ART.

During 188,952 person-years of follow-up (median, 3.0 [IQR, 1.6-4.4] years), 1243 (2.0%) patients died. Patients receiving efavirenz-based ART were more likely to be lost to follow-up compared with those on other ART regimens.

The researchers found little evidence that the risk of mortality was decreased among patients receiving rilpivirine-based ART vs those who receiving either dolutegravir-based ART (adjusted hazard ratio [aHR], 0.78; 95% CI, 0.55-1.10). The risk for all-cause mortality also was not significantly different between patients on rilpirvirine- vs elvitegravir-based ART (aHR, 0.93; 95% CI, 0.68-1.20), or between those on efavirenz- vs elvitegravir-based ART (aHR, 0.87; 95% CI, 0.64-1.18).

Further analysis showed that the risk of mortality was increased when the initial treatment was raltgegravir-based ART compared with both dolutegravir-based ARTaHR, 1.49, 95% CI 1.15-1.94) and elvitegravir-based ART (aHR, 1.86, 95% CI 1.43-2.42). Initiating treatment with raltegravir-based ART also increased the risk of mortality when compared with rilpivirine-based ART (aHR 1.99, 95% CI 1.49-2.66), darunavir-based ART (aHR 1.62, 95% CI 1.33-1.98), and efavirenz-based ART (aHR 2.12, 95% CI 1.60-2.81). Dolutegravir had higher rates of virological suppression compared to the other drugs.

These results remained consistent when adjustments were made for missing data and for the period of ART initiation (2013-2015 and 2016-2018).

Limitations included that the majority of patients were men, as well as the possibility of residual or unmeasured cofounding. In additions, these findings may be generalizable to only HIV-positive individuals residing in high-income countries.

“Although unmeasured confounding cannot be excluded as an explanation for [these] findings, virologic benefits of first-line INSTI-based ART might not translate to differences in mortality,” the researchers concluded.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Trickey A, Zhang L, Gill MJ, et al. Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study. Lancet HIV. 2022;9(6):e404-e413. doi: 10.1016/S2352-3018(22)00046-7