Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: Results from the SCOLTA project long-term surveillance.

Muscle alterations ranging from asymptomatic creatine phosphokinase (CPK) increases to rhabdomyolysis and central nervous system (CNS) symptoms have been reported in patients receiving raltegravir. Muscle symptoms and CPK increases were investigated in a cohort of HIV-infected patients receiving raltegravir-based antiretroviral therapy, and possible associated predictors were evaluated. The SCOLTA Project is a prospective, observational, multicentre study created to assess the incidence of adverse events in patients receiving new antiretroviral drugs in clinical practice. In total, 496 HIV-infected patients were enrolled [333 (67.1%) male]. CDC stage was C in 196 patients (39.5%). Mean age at enrolment was 45.9 ± 9.3 years. Median follow-up was 21 months. Twenty-six patients (5.2%) reported muscle symptoms (16 muscle pain and 17 weakness; 7 had both). Of 342 patients with normal baseline CPK values, 72 (21.1%) had a CPK increase. Seven patients (1.4%) discontinued raltegravir because of muscular events (three for muscle pain/weakness and four CPK increases). No cases of rhabdomyolysis were observed. Patients with muscle symptoms were more frequently receiving in their regimen than those not receiving atazanavir (P=0.04) and were more likely to also report CNS symptoms (P<0.0001). Significant predictors of muscle symptoms were CNS symptoms and use of atazanavir. Female sex was associated with a reduced risk of CPK increase. In conclusion, muscle symptoms and CPK elevations occurred frequently and caused most discontinuations due to adverse events. Their monitoring in patients receiving raltegravir should be considered, especially when co-administered with atazanavir or when CNS symptoms are also present.

Low bone mineral density in institutionalized patients with HIV and psychiatric co-morbidity.

Osteoporosis occurs in HIV-infected patients as well as in common psychiatric conditions and causes significant morbidity. There are no published studies assessing bone mineral density (BMD) in institutionalized HIV patients with associated psychiatric disorders. We analyzed 51 subjects in a case control study: 17 HIV patients (males or pre-menopausal females) with psychiatric co-morbidity and a long-term antipsychotic and antiretroviral therapy; and 34 control healthy subjects, not infected with HIV, matched with patients by age and sex. The results show that the HIV group had significantly higher rates of pathological T-scores, as compared with the controls (71% vs. 9% p<0.001). Chronic mental illness may represent a possible important co-factor influencing BMD in HIV patients. We suggest that fracture risk should be carefully evaluated for institutionalized HIV patients with psychiatric co-morbidity.

Aortic stiffness in untreated adult patients with human immunodeficiency virus infection.

HIV infection is associated with chronic immune activation, subclinical inflammation, and an atherogenic metabolic profile. It remains controversial whether HIV infection is a risk factor for accelerated arteriosclerosis independent from the effects of antiretroviral drugs. We investigated whether aortic stiffness, an early marker of arteriosclerosis, is increased in HIV patients who were not under antiretroviral treatment. In 39 untreated HIV-infected patients and 78 individually matched age-, sex-, and blood pressure-matched HIV-uninfected control subjects, we determined aortic pulse wave velocity (PWV), a direct noninvasive measure of aortic stiffness, by tonometric method. Subjects with overt cardiovascular disease or major cardiovascular risk factors were excluded from the study. Prevalence of the metabolic syndrome was higher in HIV patients (18% versus 5%; P=0.025). HIV patients had a higher aortic PWV (7.5+/-1.4 versus 6.7+/-1.1 m.s(-1); P=0.001) than control subjects. Age, mean arterial pressure as a measure of distending pressure, and HIV infection (all P<0.05) independently predicted aortic PWV when a consistent number of cardiovascular risk factors was simultaneously controlled for. Among HIV-infected subjects, serum gamma-glutamyl transpeptidase concentration (beta=0.46; P=0.003) and mean arterial pressure (beta=0.32; P=0.03) were independent determinants of aortic PWV. In conclusion, aortic stiffness is increased in HIV-infected individuals who have never received antiretroviral therapy. PWV increases with increasing serum gamma-glutamyl transpeptidase concentration. Our data support the hypothesis that HIV infection is a risk factor for arteriosclerosis.

Impact of treatment with protease inhibitors on aortic stiffness in adult patients with human immunodeficiency virus infection.

BACKGROUND: The role of antiretroviral therapy in acceleration of atherosclerosis in patients with human immunodeficiency virus (HIV) infection is controversial. We hypothesized that aortic stiffness, an early marker of arteriosclerosis, may be increased in HIV patients treated with protease inhibitors. METHODS AND RESULTS: In 32 HIV-infected patients treated with protease inhibitors and 32 age-, sex-, and blood pressure-matched HIV-uninfected control subjects, we obtained aortic pulse wave velocity and central aortic pressure waveform, from which aortic augmentation was calculated. HIV patients had a higher aortic pulse wave velocity (7.6+/-1.1 versus 6.8+/-1.2 m x s(-1), P=0.015) and aortic augmentation (6.8+/-5 versus 4.6+/-4 mm Hg, P=0.037) than control subjects. Age and HIV infection (both P<0.05) independently predicted aortic pulse wave velocity when a consistent number of cardiovascular risk factors was simultaneously controlled for. The cumulative duration of treatment was a predictor of aortic pulse wave velocity, each 5 years of treatment duration being independently related to a 1.35 m x s(-1) increase in pulse wave velocity. CONCLUSIONS: Aortic stiffness is increased in HIV-positive individuals receiving antiretroviral therapy including a protease inhibitor. Pulse wave velocity increases with longer exposure to protease inhibitors. We hypothesize that arteriosclerosis is a side effect of antiretroviral treatment including a protease inhibitor.