Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals.

OBJECTIVE: To compare life expectancies between recently diagnosed HIV-infected patients and age and sex-matched uninfected individuals from the general population. DESIGN: : National observational HIV cohort in the Netherlands. METHODS: Four thousand, six hundred and twelve patients diagnosed with HIV between 1998 and 2007 and still antiretroviral therapy-naive as of 24 weeks after diagnosis were selected. Progression to death compared to the age and sex-matched general population was studied with a multivariate hazards model in 4174 (90.5%) patients without AIDS events at 24 weeks. Life expectancy and number of life years lost were calculated using the predicted survival distribution. RESULTS: During 17 580 person-years of follow-up since 24 weeks after diagnosis [median follow-up 3.3 years, interquartile range (IQR) 1.6-5.8], 118 deaths occurred, yielding a mortality rate of 6.7 [95% confidence interval (CI) 5.5-8.0] per 1000 person-years. Median CD4 cell counts at 24 weeks were 480 cells/microl (IQR 360-650). According to the model, the median number of years lived from age 25 was 52.7 (IQR 44.2-59.3; general population 53.1) for men and 57.8 (49.2-63.7; 58.1) for women without CDC-B event. The number of life years lost varied between 0.4 if diagnosed with HIV at age 25 and 1.4 if diagnosed at age 55; for patients with a CDC-B event this range was 1.8-8.0 years. CONCLUSION: The life expectancy of asymptomatic HIV-infected patients who are still treatment-naive and have not experienced a CDC-B or C event at 24 weeks after diagnosis approaches that of non-infected individuals. However, follow-up time is short compared to the expected number of years lived.

Which method of adherence measurement is most suitable for daily use to predict virological failure among immigrant and non-immigrant HIV-1 infected patients?

In industrialized countries, virological failure occurs more often among HIV-infected immigrant patients. Non-adherence is the most credible explanation. We compared adherence of immigrant patients with that of non-immigrant patients in the Netherlands, and investigated which method of adherence measurement is most suitable for daily use to predict virological treatment failure: testing knowledge of the current regimen, a quantitative adherence interview, pharmacy prescription refill ratio (dispensed medication divided by prescribed medication, DM/PM), and plasma drug levels. Included were 61 immigrants and 81 non-immigrants. Virological failure did occur more often in immigrants than in non-immigrants (19.7% (12/61) versus 8.6% (7/81), p=0.056), especially among previously naive patients (19.6% (11/56) versus 0% (0/54), p<0.01). There were no differences between both groups on any of the four adherence measures. Virological failure was associated with reporting stopping medication when not feeling well (OR=12, 95%CI=1.9-77.7, p=0.02), and, among naive patients, also with a DM/PM < 0.85 (Odds Ratio=5.1, 95%Confidence Interval=1.2-22.3, p=0.03). Although our study confirmed a much higher virological failure rate among immigrants, we were unable to identify clear differences in adherence between immigrants and non-immigrant patient, although virological failure was associated with stopping medication when not feeling well and a low DM/PM. Unstructured treatment interruptions are a likely explanation of the findings. Interventions should be aimed at preventing patients to stop medication. A DM/PM below 0.85 can be indicative for patients who did stop medication and are at risk for virological failure.