This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.

Aims To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non‐nucleoside reverse transcriptase inhibitor efavirenz. Methods Data from all samples analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed. Information on gender, age, body weight, height, race, hormonal contraceptive use (in a subset of patients), and time between sampling and last intake was recorded. PCR‐restriction fragment length polymorphism analysis was performed to detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and CYP2B6*7) which is associated with low CYP2B6 activity. Results A total of 255 patients were included in this analysis. The median plasma efavirenz concentration was 2.50 (interquartile range: 1.85–3.55) mg l−1. Eight patients (3.1%) were considered to have a subtherapeutic plasma concentration (<1.0 mg l−1) and 48 (18.9%) a toxic efavirenz concentration (>4.0 mg l−1). Gender, time after last intake, and race were the only factors that were significantly related to plasma efavirenz concentration in a multivariate analysis. No influence was observed for body weight, hormonal contraceptive use, and the presence of the CYP2B6 C1459T polymorphism. Conclusions Gender and race are important factors in determining interpatient variability in plasma efavirenz concentrations which were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians should be particularly alert for signs of efavirenz‐induced toxicity in females and non‐Caucasian patients.

Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.

To cite this article: Lijfering WM, ten Kate MK, Sprenger HG, van der Meer J. Absolute risk of venous and arterial thrombosis in HIV-infected patients and effects of combination antiretroviral therapy.

Background: HIV-infected patients are at increased risk of venous and arterial thrombosis. We hypothesized that acquired thrombophilic abnormalities that could predispose to thrombosis are most pronounced in patients in advanced stages of HIV infection. Methods: We included 109 consecutive HIV-infected patients in the study and tested them twice for currently known thrombophilic abnormalities at an interval of at least 3 months (median, 3 months; range, 3–12 months). Detailed information was collected about the date of diagnosis of HIV infection, HIV treatment, and previous episodes of venous and arterial thrombosis. Results: After HIV infection was diagnosed, 16% of the patients experienced symptomatic thrombosis (venous, 10%; arterial, 6%). Repeated measurements established protein C deficiency in 9% of the patients, increased factor VIII concentrations in 41%, high fibrinogen concentrations in 22%, and free protein S deficiency in 60%. Median factor VIII concentrations were higher in patients with AIDS (CD4 cell counts &lt;2 × 108/L) than in patients with a non–AIDS-defining illness (2260 IU/L vs 1 490 IU/L; P &lt; 0.001), whereas median free protein S concentrations were lower (450 IU/L vs 580 IU/L; P &lt; 0.001). Developing AIDS was associated with increasing factor VIII concentrations and decreasing free protein S concentrations. Increasing factor VIII concentrations were correlated with increasing fibrinogen concentrations and decreasing free protein S concentrations. Conclusions: Multiple acquired and persistent thrombophilic abnormalities are more frequently observed in HIV-infected patients than in the healthy population. The frequencies of these thrombophilic abnormalities increase with the progression to AIDS. These findings may contribute to the high prevalence of venous and arterial thrombosis in HIV-infected patients.