ObjectivesWith the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its treatment. This study was designed to explore these issues. MethodsDemographic information and fasting blood samples were collected from 419 antiretroviral-naïve HIV-1-infected patients. ResultsThe average age of the participants was 38.2 years, with 21% being female, 60% being African American, and 14% having a history of injection drug use. The mean CD4 lymphocyte count was 216 cells/mL, the mean baseline log 10 HIV viral load was 4.98 HIV-1 RNA copies/mL, and 26% of patients had a history of AIDS-defining events. Women and African Americans had significantly higher levels of high-density lipoprotein (HDL) cholesterol, and older age was associated with higher total cholesterol levels. Lower CD4 lymphocyte counts and higher HIV RNA levels were independently associated with lower HDL cholesterol levels. Additionally, higher HIV RNA level was associated with lower levels of low-density lipoprotein (LDL) cholesterol and higher levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides. A history of AIDS-defining events was associated with higher total cholesterol, VLDL cholesterol and triglyceride concentrations. With respect to glucose homeostasis, a higher CD4 lymphocyte count was associated with less evidence of insulin resistance. However, a higher body mass index was associated with higher lipid levels and with more evidence of insulin resistance. ConclusionsBoth HIV disease and demographic characteristics were found to influence lipid values and glucose homeostasis in the absence of antiretroviral treatment. More advanced HIV disease was associated with less favourable lipid and glucose homeostatic profiles. The independent association between HIV RNA levels and various lipid parameters suggests that viral replication had a direct effect on lipid levels. Interpretation of the effects of various HIV treatment regimen and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied.

The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) Study, a prospective observational study on a cohort of 23 468 patients with HIV infection, indicated that the incidence of myocardial infarction (MI) increased by 26% per year of exposure to combination antiretroviral treatment (CART). However, it remains unclear whether the observed increase in the rate of MI in this population can be attributed to changes in conventional cardiovascular risk factors. ObjectiveTo compare the number of MIs observed among participants in the D:A:D Study with the number predicted by assuming that conventional cardiovascular risk equations apply to patients with HIV infection. MethodsThe Framingham equation, a conventional cardiovascular risk algorithm, was applied to individual patient data in the D:A:D Study to predict rates of MI by duration of CART. A series of sensitivity analyses were performed to assess the effect of model and data assumptions. Predictions were extrapolated to provide 10-year risk estimates, and various scenarios were modelled to assess the expected effect of different interventions. ResultsIn patients receiving CART, the observed numbers of MIs during D:A:D follow up were similar to or somewhat higher than predicted numbers: 9 observed vs 5.5 events predicted, 14 vs 9.8, 22 vs 14.9, 31 vs 23.2 and 47 vs 37.0 foro1 year, 1-2 years, 2-3 years, 3-4 years and 44 years CART exposure, respectively. In patients who had not received CART, the observed number of MIs was fewer than predicted (3 observed vs 7.6 predicted). Nine per cent of the study population have a predicted 10-year risk of MI above 10%, a level usually associated with initiation of intervention on risk factors. ConclusionsA consistent feature of all analyses was that observed and predicted rates of MI increased in a parallel fashion with increased CART duration, suggesting that the observed increase in risk of MI may at least in part be explained by CART-induced changes in conventional risk factors. These , to predict the rate of MI that would have been expected during the D:A:D Study follow up based on patients' risk factors for CVD and to compare this with the observed rate. This would allow an assessment of whether the overall cardiovascular risk in HIV-infected individuals in the D:A:D Study is similar to that among uninfected patients with similar risk profiles. In addition, this analysis would also help to determine whether the observed increased risk of MI with duration of CART can be explained by changes in conventional cardiovascular risk factors that occur over time. We hypothesized that, if the increased risk was mediated through such risk factors, then it would be expected that the predicted rates of MI would parallel the increased rates observed with increasing duration of CART during follow up, both overall and according to age and gender [15][16][17].A basic principle of prevention is that the intensity of risk-reduction measures should be adjusted to a person's absolute risk. Various preventive guidelines have been de...

Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered among all individuals exposed for longer time periods. The use of d-drugs should furthermore be avoided, where there are alternatives available, and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis-independent, TDF association calls for further investigations.