RESUMEN
People living with HIV (PLWH) have a risk of cardiovascular disease (CVD) that is 1.5 to 2 times higher than the general population owing to traditional risk factors, HIV-mediated factors like chronic inflammation and immune dysfunction, and exposure to antiretroviral therapy. Currently available CVD risk estimation calculators tend to underestimate risk in PLWH but can be useful when an individual's HIV history is considered. Improving modifiable risks is the primary intervention for reducing CVD risk in PLWH. Statin therapy is important for specific individuals, but attention should be given to drug interactions with antiretroviral agents used to treat HIV.
Asunto(s)
Enfermedades Cardiovasculares , Infecciones por VIH , Prevención Primaria , Humanos , Enfermedades Cardiovasculares/prevención & control , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/prevención & control , Prevención Primaria/métodos , Factores de Riesgo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Integrase strand transfer inhibitors (INSTIs) have become integral antiretroviral therapy (ART) agents for treating HIV infection. We report the case of a 44-year-old male with a history of hemophilia A who developed diabetes mellitus four months after switching from abacavir, lamivudine, and efavirenz to abacavir, lamivudine, and raltegravir. Hemoglobin A1C normalized without further need for exogenous insulin after raltegravir was switched back to efavirenz. In this case report, we will review a possible mechanism for INSTI-induced hyperglycemia and/or diabetes mellitus.
Asunto(s)
Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/patología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/efectos adversos , Adulto , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/efectos adversos , Combinación de Medicamentos , Hemoglobina Glucada/análisis , Inhibidores de Integrasa VIH/administración & dosificación , Humanos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Masculino , Raltegravir Potásico/administración & dosificación , Raltegravir Potásico/efectos adversosRESUMEN
OBJECTIVES: This open-label, single-arm, pharmacokinetic (PK) study in HIV-seronegative volunteers evaluated the bioequivalence of rosuvastatin and lopinavir/ritonavir when administered alone and in combination. Tolerability and lipid changes were also assessed. METHODS: Subjects took 20 mg of rosuvastatin alone for 7 days, then lopinavir/ritonavir alone for 10 days, and then the combination for 7 days. Intensive PK sampling was performed on days 7, 17, and 24. RESULTS: Twenty subjects enrolled, and PK data were available for 15 subjects. Geometric mean (+/-SD) rosuvastatin area under the concentration time curve (AUC)[0,tau] and maximum concentration (Cmax) were 47.6 ng.h/mL (+/-15.3) and 4.34 ng/mL (+/-1.8), respectively, when given alone versus 98.8 ng.h/mL (+/-65.5) and 20.2 ng/mL (+/-16.9) when combined with lopinavir/ritonavir (P < 0.0001). The geometric mean ratio was 2.1 (90% confidence interval [CI]: 1.7 to 2.6) for rosuvastatin AUC[0,tau] and 4.7 (90% CI: 3.4 to 6.4) for rosuvastatin Cmax with lopinavir/ritonavir versus rosuvastatin alone (P < 0.0001). There was 1 asymptomatic creatine phosphokinase elevation 17 times the upper limit of normal (ULN) and 1 liver function test elevation between 1.1 and 2.5 times the ULN with the combination. CONCLUSIONS: Rosuvastatin low-density lipoprotein reduction was attenuated with lopinavir/ritonavir. Rosuvastatin AUC and Cmax were unexpectedly increased 2.1- and 4.7-fold in combination with lopinavir/ritonavir. Rosuvastatin and lopinavir/ritonavir should be used with caution until the safety, efficacy, and appropriate dosing of this combination have been demonstrated in larger populations.