title: [Safety profile of dolutegravir].
abstract: Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers.
authors: Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba-IMIBIC, España.
authors: Antonio
authors: A
authors: Rivero
authors: Unidad de Enfermedades Infecciosas, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España. Electronic address: pdomingo@santpau.cat.
authors: Pere
authors: P
authors: Domingo
mesh_terms: D016723:Bone Remodeling / Q000187:drug effects; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D004342:Drug Hypersensitivity / Q000209:etiology; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006261:Headache / Q000139:chemically induced; D006525:Hepatitis, Viral, Human / Q000150:complications; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced; D007684:Kidney Tubules / Q000187:drug effects; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D019964:Mood Disorders / Q000139:chemically induced; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors; D000075102:Organic Cation Transporter 2; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012120:Respiration Disorders / Q000139:chemically induced; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D000099226:Dolutegravir; D000099227:Abacavir
chemical_list: D003404:Creatinine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D019259:Lamivudine; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099226:Dolutegravir; C491013:SLC22A2 protein, human; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir
keywords: Adverse effects; Bone remodeling markers; Creatinina; Creatinine; Dolutegravir; Efectos adversos; Inhibidores de la integrasa; Integrase inhibitors; Marcadores de remodelado óseo; Tolerabilidad; Tolerability