Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study.

AIMS: HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. METHODS AND RESULTS: Prospective multinational cohort study. The data set included 22,625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti-HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score. The models included age, sex, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, HDL cholesterol and indinavir, lopinavir/r and abacavir exposure. The models performed well with area under the receiver operator curve statistics of 0.783 (range 0.642-0.820) for myocardial infarction, 0.776 (0.670-0.818) for coronary heart disease and 0.769 (0.695-0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. CONCLUSION: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs, might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models.

Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe.

BACKGROUND: Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce. METHODS: All HIV-positive patients living in Europe and Argentina recruited in EuroSIDA (1994-2006) were tested for serum HBV surface antigen (HBsAg). Chronic carriers were further characterized virologically at one central laboratory. Variables influencing HBV genotype distribution and viraemia were assessed using logistic regression. RESULTS: From 16 505 HIV patients enrolled in EuroSIDA, 1179 (7.1%) were HBsAg positive, of whom 474 had specimens that allowed inclusion in the virological substudy. Overall 293 (62%) were treated with anti-HBV active antiretroviral drugs at the time of testing. Hepatitis delta virus superinfection was recognized in 14% and hepatitis C virus (HCV) antibodies in 27%. Serum HBV DNA was detectable in 315 (66.5%) and HBV genotyping gave results in 170 (35.9%) patients. HBV genotype distribution was as follows: A (72.9%), D (17.1%), G (1.8%), E (1.2%), F (1.2%) and C (0.6%); another 5.9% were co-infected with multiple HBV genotypes. In the multivariate analysis, the best predictor of HBV genotype A infection was risk exposure other than intravenous drug use, whereas predictors for detectable HBV viraemia were lower CD4 counts and lack of HCV antibodies. CONCLUSION: A substantial proportion of HIV-positive patients with chronic hepatitis B show detectable HBV viraemia despite being treated with anti-HBV active antiretroviral drugs (mainly lamivudine). Low CD4 counts were associated with an independent higher risk of detectable HBV viraemia, which supports an earlier introduction of antiretroviral therapy, including anti-HBV drug(s) more potent than lamivudine.

Risk of discontinuation of nevirapine due to toxicities in antiretroviral-naive and -experienced HIV-infected patients with high and low CD4+ T-cell counts.

INTRODUCTION: It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients. PATIENTS AND METHODS: 1,571 EuroSIDA patients started NVPc after 1/1/1999, with CD4+ T-cell counts and viral load measured in the 6 months before starting treatment, and were stratified into four groups based on CD4+ T-cell counts at initiation of NVPc (high [H], > 400/mm3 or > 250/mm3 for male or female, respectively, or low [L], < or = 400/mm3 or 5250/mm3 for male or female) and prior antiretroviral experience (antiretroviral-naive [N] or -experienced [E]). Cox proportional hazards models compared the risks of discontinuation of nevirapine due to toxicities or patient/physician choice (TOXPC). RESULTS: After adjustment, there was a significantly lower risk of discontinuation of nevirapine due to TOXPC in the HE group (n = 588; proportion discontinued by 3/12 months: 10/17%, respectively) than in HN (n = 62; 21/32% respectively; overall relative hazard [RH]: 0.56; 95% confidence interval [CI]: 0.34-0.94; P = 0.027). This difference was most pronounced during the first 3 months of NVPc (RH: 0.44; 95% CI: 0.23-0.87; P = 0.017). There were no deaths in the 6 months after starting NVPc resulting from exposure to < 3 months of NVPc exposure within the HE group (incidence: 0; per 1,000 person-years follow up; 95% CI: 0-6.9). After adjustment, there were no differences between the HE and HN groups in discontinuation due to TOXPC in patients starting efavirenz-based cART (RH: 0.91; 95% CI: 0.60-1.38; P = 0.66) or protease-inhibitor-based cART (RH: 1.13; 95% CI: 0.77-1.66; P = 0.52). CONCLUSIONS: Results from this non-randomized study suggest that NVPc might be safer to initiate in antiretroviral-experienced than in antiretroviral-naive patients with high CD4+ T-cell counts.