Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers.

BACKGROUND: As those with HIV infection live longer, 'non-AIDS' condition associated with immunodeficiency and chronic inflammation are more common. We ask whether 'non-HIV' biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART). METHODS: Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. RESULTS: Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P < 0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data. CONCLUSIONS: When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.

Reduced aerobic capacity and physical functioning in older HIV-infected men.

Aerobic capacity and physical functioning decline with age and chronic illness. The extent of physical disability is unknown in older HIV-infected adults, who represent a rapidly growing proportion of HIV/AIDS patients in the United States. We performed functional performance testing including treadmill testing in 32 HIV-infected male veterans aged 40-69 years. Controls were 47 healthy male subjects tested previously in the same exercise laboratory. HIV-infected subjects were classified as younger (40-49 years, n = 12) or older age (50+ years, n = 20). Peak aerobic capacity (VO2peak) was significantly reduced in the older vs. younger HIV subjects [19.1 mL/kg/min +/- 5.7 (mean, SD) vs. 25.2 +/- 4.2, p = 0.01]. VO2peak was reduced 41% +/- 15% (mean, SD) in HIV-infected subjects compared to expected values from age-matched healthy controls. Regression analyses show a similar decline in VO2peak with age in HIV-infected and healthy controls. Mean 6-min walk distance was not significantly different between the HIV-infected age groups, and was reduced only 8% compared to expected values for healthy adults. Current CD4 count and HAART exposure were similar in the two age groups and were not significantly associated with VO2peak. Anemia (HCT <35%) was significantly associated with reduced VO2peak (p = 0.02), but this association was not independent of the effect of age (p = 0.1). We conclude that older HIV-infected adults have markedly impaired aerobic capacity but maintain the capacity to undertake day-to-day activities. Additional physiologic and metabolic testing is needed to measure the effect of HAART toxicity and primary aging on aerobic capacity, and to determine if older HIV-infected adults are at greater risk.