Outcome of Darunavir–Cobicistat-Based Regimens in HIV-Infected People Who Have Experienced Virological Failure

Abstract

Objective

To evaluate the virological outcome of darunavir–cobicistat (DRVc)‐based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination.

Methods

This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc‐based regimen with HIV‐RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV‐RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or loss to follow‐up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS.

Results

A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV‐RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004–1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant–bearing protease inhibitor–resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up.

Conclusion

Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.

Keywords:

• HIV infection
• antiretroviral therapy
• ART
• darunavir–cobicistat
• DRVc
• virological failure
• VF

Ethics and Consent

Individuals provided written informed consent to the use of their data in scientific analyses and to be included in the Centro San Luigi (CSL) HIV Cohort. The CSL-HIV Cohort was approved by the Ethics Committee of the IRCCS San Raffaele Scientific Institute (Milan, Italy; date of approval 4th December 4, 2017, protocol 34). The study described in the manuscript was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki.

Acknowledgments

The authors thank Diana Canetti for medical writing on behalf of the IRCCS San Raffaele Scientific Institute and Johnson & Johnson Italy.

Disclosure

AC has received personal fees for advisory boards, speaker panels, and educational materials from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme, and Theratechnologies. NG has been an advisor for Gilead Sciences, Janssen-Cilag, ViiV Healthcare and Merck Sharp & Dohme and has received speakers’ honoraria from Gilead Sciences, ViiV Healthcare, Janssen-Cilag and Merck Sharp & Dohme. FA, LG, RL, CC, MC, MR, MS declare no competing interests. AU is an employee of Johnson & Johnson Italy.

Additional information

Funding

This analysis was funded by Johnson & Johnson Italy.