Durability of INI-containing regimens after switching from PI-containing regimens: a single-centre cohort of drug-experienced HIV-infected subjects

Abstract

Purpose

Integrase inhibitor (INI)-containing regimens are increasingly replacing protease inhibitor(PI)-containing regimens in clinical practice. The aim of this study was to evaluate the determinants of the durability of INI-containing regimens after the switch.

Patients and methods

We retrospectively analysed all of the people with HIV infection attending the University of Milan’s Infectious Diseases Unit at Luigi Sacco Hospital who were switched from a PI- to an INI-containing regimen between April 2008 and March 2017. The probability of remaining on an INI-containing regimen was estimated using Kaplan-Meier curves, and the baseline clinical predictors of INI-containing regimen durability were assessed using a multivariable Cox proportional hazard regression model.

Results

Three hundred and twelve patients were included in the analysis. The median time of observation was 21 months (interquartile range 10–36 months). The main reasons for switching from a PI-containing regimen to an INI-containing regimen were toxicities (31.4%) and simplification (31.1%). Univariate analysis revealed no difference in the probability of INI discontinuation between the patients treated with raltegravir, dolutegravir or elvitegravir (p=0.060), but the multivariable Cox regression model showed that the patients treated with dolutegravir were at less risk of discontinuation than those treated with raltegravir (adjusted hazard ratio 0.49, 95% confidence interval 0.26–0.95; p=0.034).

Conclusion

Switching from a PI- to an INI-containing regimen may be an option for patients under virological control. The patients switched to dolutegravir were less likely to discontinue the INI than those switched to raltegravir. Our findings support this therapeutic strategy and highlight the durability and efficacy of dolutegravir containing-regimens after switching from a PI-containing regimen.

Keywords:

• HIV
• protease inhibitors
• integrase inhibitors
• dolutegravir
• lipids
• Framingham

Acknowledgment

We would like to thank Mrs Tiziana Formenti for her excellent technical help.

Abbreviation list

PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; INI, integrase inhibitor; RAL, raltegravir; EVG, elvitegravir; DTG, dolutegravir; ub, unboosted; LPV, lopinavir; fAPV, fosamprenavir; ATV, atazanavir; DRV, darunavir; IQR, interquartile range; CI, confidence interval; cART, combined antiretroviral therapy; STR, single tablet regimen; TC, total cholesterol; TG, triglycerides; DAA, direct antiviral agents.

Ethics approval and informed consent

The protocol was reviewed and approved by the Comitato Etico Interaziendale Milano Area 1, and an informed consent form was signed by all of the subjects who participated in this study.

Data availability

Data will be made available upon reasonable request.

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

SR has received research grants, consultancy payments and speaker’s fees from Bristol-Myers Squibb, Gilead, ViiV Healthcare, Merck Sharp Dohme, ABBvie and Janssen. MG has received research grants, consultancy payments and speaker’s fees from Bristol-Myers Squibb, Gilead, ViiV Healthcare, Merck Sharp Dohme, ABBvie, Janssen and Roche. The authors report no other conflicts of interest in this work.