Tolerability of integrase inhibitors in a real-life setting.
Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them.



We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients.



Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit. Major outcomes were early discontinuation (≤1 year) due to any reason and more specifically due to toxicity. Incidence was calculated as number of episodes per 1000 person-years. Risk factors for discontinuation were assessed by multivariate Cox models.



Early discontinuations due to any reason were 271 (raltegravir), 168 (elvitegravir) and 264 (dolutegravir) per 1000 patient-years ( P  =   0.0821). Early discontinuations due to toxicity were 76 (raltegravir), 103 (elvitegravir) and 81 (dolutegravir) per 1000 patient-years ( P  =   0.6792). Overall, the most common toxicities leading to discontinuation were neuropsychiatric, osteomuscular or digestive. Most frequent neuropsychiatric manifestations reported at discontinuation were insomnia, dizziness, headache and anxiety irrespective of the integrase inhibitor. Among discontinuations due to toxicity, neuropsychiatric effects were more common with dolutegravir than with raltegravir or elvitegravir ( P  =   0.0046). Age (HR 1.04, 95% CI 1.02-1.07, P  =   0.0007) was the only independent risk factor for early discontinuation due to toxicity.



Discontinuations due to any reason tended to be less common with elvitegravir, but discontinuations due to toxicity did not differ among integrase inhibitors. Neuropsychiatric toxicity leading to drug discontinuation was more frequent with dolutegravir.
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Judit
J
Peñafiel
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Elisa
E
de Lazzari
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Mireia
M
Padilla
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Jhon
J
Rojas
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Ana
A
Gonzalez-Cordon
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Jose L
JL
Blanco
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Jordi
J
Blanch
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Maria A
MA
Marcos
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Montserrat
M
Lonca
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Maria
M
Martinez-Rebollar
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Montserrat
M
Laguno
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Amparo
A
Tricas
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Ana
A
Rodriguez
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Josep
J
Mallolas
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Jose M
JM
Gatell
Hospital Clínic, University of Barcelona, Barcelona, Spain.
Esteban
E
Martinez
D000328:Adult; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008019:Life Style; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D016016:Proportional Hazards Models; D011728:Pyridones; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use / Q000633:toxicity; D000068898:Raltegravir Potassium / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D000099226:Dolutegravir
D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D015363:Quinolones; D000068898:Raltegravir Potassium; D000099226:Dolutegravir; C509700:elvitegravir