Adverse Events of Raltegravir and Dolutegravir

Luigia Elzi; Stefan Erb; Hansjakob Furrer; Matthias Cavassini; Alexandra Calmy; Pietro Vernazza; Huldrych Günthard; Enos Bernasconi; Manuel Battegay

Disclosures

AIDS. 2017;31(13):1853-1858. 

In This Article

Methods

Study Setting

We analysed the Swiss HIV Cohort Study (SHCS) database, a large prospective and ongoing cohort study in Switzerland with continuous enrolment of HIV-infected individuals of 16 years or older. In the SHCS, basic sociodemographic characteristics, clinical course, ART, reasons for discontinuation or change of the ART regime, comedication, immunological, and virological data as well as information on comorbidity and coinfections are collected at registration into the study and every 6 months thereafter on standardized protocols. For the present analysis we used SHCS database update of January 2017.

Study Population

All HIV-infected individuals participating in the SHCS starting an antiretroviral regime containing raltegravir or dolutegravir combined with appropriate backbone between 1 April 2006 and 31 December 2015 and who had a follow-up of at least 12 months were eligible for this study.

Definitions

Treatment modification was defined as discontinuation or switch of ART within the first year of treatment. Discontinuation was defined as stopping dolutegravir or raltegravir for at least 4 weeks. A switch to another regimen was defined as changing one or more drugs within 4 weeks after stopping ART. The main reason for treatment modification was classified as treatment failure, intolerance, and/or toxic effects, the patient's choice, the physician's decision, and other reasons. Since 2014 more detailed reasons for drug discontinuation were introduced and prospectively collected in the SHCS database, including treatment simplification, concerns about drug interactions and adherence. Toxicity, predominantly from the nervous system was specifically coded detailed as neuropsychiatric toxicity, headache, or peripheral neuropathy.

Statistical Analysis

The primary endpoint was the time to first treatment modification (i.e., switch to another antiretroviral regime or discontinuation) during the first year of treatment. Basic sociodemographic characteristics, CD4+ cell counts, HIV RNA, and ART were compared using the [chi][2] test for categorical and Mann–Whitney U or Kruskal–Wallis test for continuous variables. We used Kaplan–Meier curves to describe the cumulative incidence of treatment modification according to either raltegravir or dolutegravir-containing ART regimen, and the curves were compared using log-rank tests. Uni and multivariable Cox regression analysis was used to investigate risk factors for treatment modification because of any reason and because of adverse events. The following variables were assessed: sex, age, ethnicity, prior AIDS-defining condition, hepatitis C virus coinfection, CD4+ cell count, HIV RNA, treatment status, ART backbone (abacavir–lamivudine versus tenofovir–emtricitabine versus other) and INSTI (raltegravir versus dolutegravir).

All patients were censored at 1 year after starting ART if no treatment modification or death had occurred. P values < 0.05 were considered statistically significant. All analyses were performed using commercially available software (STATA, version 13.1 for Windows, StataCorp, College Station, Texas, USA).

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