“The observed rate of viral failure during follow-up was lower among people living with HIV initiating dolutegravir-based vs darunavir-based regimens in routine clinical care sites across the US,” reports Dr Heidi M Crane, from the University of Washington in Seattle in an IDWeek 2017 presentation. Much of the existing literature on viral failure with integrase inhibitors is based on clinical trial results rather than clinical care settings, and little is known about recently approved agents, Crane said.
The research team compared viral failure rates among HIV patients who initiated on dolutegravir-based vs other guideline recommended regimens in real-world clinical care settings. A total of 5,177 patients across 8 CFAR Network of Integrated Clinical Systems (CNICS) sites who were initiated on a recommended regimen between August 2013 to March 2017 were included for analysis.
The researchers compared viral failure among patients initiated on dolutegravir vs. other INSTI regimens, and dolutegravir vs. darunavir-based regimens that are a part of current guidelines for starting antiretroviral therapy (ART).
Viral failure (VF) was defined as a viral load of >400 copies/mL >6 months after initiation, explained Crane. Multivariate models were adjusted for age, gender, race/ethnicity, hepatitis B/C, tuberculosis, HIV risk factor, CD4 count, days since last HIV viral load, and site.
Patients who were initiated on a dolutegravir-based regimen experienced fewer viral failures than those on darunavir-based regimen (hazard ratio [HR] 0.41, 95% CI: 0.30–0.55).
“The HR for dolutegravir vs. darunavir-based regimens ranged from 0.40 to 0.50 depending on censoring definitions for end of follow-up, but these associations were all (statistically) significant,” she said.
Background: Much of the prior research on viral failure (VF) with integrase inhibitor (INSTI) therapy is based on results from trials rather than clinical care settings and little is known about recently approved medications such as dolutegravir (DTG). We compared VF in persons living with HIV (PLWH) who initiated DTG-based vs. other guideline recommended regimens in clinical care across the U.S.
Methods: PLWH from 8 CFAR Network of Integrated Clinical Systems (CNICS) sites who started a recommended regimen between 8/2013-8/2016 were included. We compared DTG vs. other INSTI, and vs. darunavir-based (DRV) regimens included in current guidelines for initiating antiretroviral therapy (ART). VF was defined as a viral load of >400 copies/mL >6 months after initiation. We used Cox models adjusting for age, sex, race/ethnicity, hepatitis B, hepatitis C, tuberculosis, HIV risk factor, CD4 count, days since last HIV viral load, and site. PLWH were censored at death, regimen change or loss to follow-up (LTFU) with sensitivity analyses varying LTFU definitions from 0-12 months after last activity and including/excluding inverse probability censoring weights based on variables in the main models.
Results: Among 6636 PLWH who initiated a recommended regimen, a lower proportion on DTG-based regimens experienced VF during follow-up (Figure). The adjusted hazard ratio (HR) for VF for DTG vs. DRV-based regimens was 0.56 (95% confidence interval 0.37-0.86). In sensitivity models, the HR for VF for DTG vs. other INSTI regimens ranged from 0.73-1.07 depending on LTFU definitions. The HR for DTG vs. DRV-based regimens ranged from 0.38-0.63 depending on LTFU definitions. In sensitivity analyses among the 1229 PLWH known to be ART-na•ve at initiation, a similar pattern was found with a lower HR of VF among those who initiated DTG vs. DRV-based regimens (HR 0.25, 95% CI 0.11-0.56).
Conclusion: The observed rate of VF during follow-up was lower among PLWH initiating DTG-based vs DRV-based regimens in routine clinical care at sites across the US. Results also demonstrated that different definitions of LTFU can have a large impact on the results and highlight the importance of sensitivity analyses in informing study definitions to minimise bias.
Robin Nance, Vani Vannappagari, Kimberly Smith, Catherine Johannes, Brian Calingaert, Catherine Saltus, Stephen Boswell, Benigno Rodriguez, Richard Moore, Joseph Eron, Elvin Geng, W Christopher Mathews, Michael S Saag, Mari Kitahata, JaC Delaney, Heidi M Crane