HIV Boosts Risk of Acute COPD Exacerbation in 130,000-Veteran Analysis

HIV infection independently heightened the risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in a 130,000-person Veterans Aging Cohort Study (VACS) analysis. Lower CD4+ count, smoking and unhealthy alcohol use also raised AECOPD risk.

Previous work found higher COPD prevalence in HIV populations independent of smoking history. A small study of injection drug users linked HIV infection to higher risk of AECOPD, but risk factors for AECOPD in HIV populations remain poorly characterized. VACS investigators conducted this study to compare AECOPD incidence in HIV-positive and negative veterans and to identify risk factors.

VACS researchers identified veterans with HIV and matched each to two HIV-negative veterans by age, race, sex and region. The researchers defined AECOPD as a COPD ICD-9 diagnosis plus steroid and/or antibiotic prescription within five days of diagnosis. They defined unhealthy alcohol use as one inpatient or two outpatient ICD-9 alcohol-related diagnoses. The primary outcome was time to AECOPD through two years of observation.

The study matched 43,618 veterans with HIV to 86,492 without HIV. Most study participants (98%) were men, averaged age 48 years; 48% were black, 39% white and 8% Hispanic. Almost half (48%) were current smokers, and 14% were former smokers. Among veterans with HIV, median baseline CD4+ count stood at 303 cells/mm³.

AECOPD incidence measured 18.8 per 1000 person-years in HIV-positive veterans and 13.3 per 1000 person-years in the control group (P < .001). Unadjusted AECOPD incidence was significantly higher in veterans with HIV (incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 1.32 to 1.51). Unadjusted analysis restricted to veterans with HIV determined that lower CD4+ counts were associated with a significantly greater risk of AECOPD (compared with >350 cells/mm³, <200 cells/mm³ IRR 2.12 and ≥200 to 349 cells/mm³ IRR 1.31). Taking antiretroviral therapy at study enrollment significantly lowered the risk of AECOPD (IRR 0.73, 95% CI 0.64 to 0.83).

Multivariable Poisson regression analysis determined that veterans with HIV had more than a 50% higher risk of AECOPD than HIV-negative veterans (IRR 1.54, 95% CI 1.44 to 1.65). Compared with HIV-negative veterans, HIV-positive veterans with a baseline CD4+ count <200 cells/mm³ had more than a doubled risk of AECOPD (IRR 2.30, 95% CI 2.10 to 2.53), while those with 200 to 349 cells/mm³ had a one-third higher risk (IRR 1.32, 95% CI 1.15 to 1.51). But HIV-positive veterans with a CD4+ count >350 cells/mm³ had an AECOPD risk equivalent to that of HIV-negative veterans (IRR 0.99, 95% CI 0.88 to 1.10).

Other independent AECOPD risk factors in this model included current smoking (IRR 2.47, 95% CI 2.22 to 2.75), past smoking (IRR 1.67, 95% CI 1.47 to 1.90) and unhealthy alcohol use (IRR 1.54, 95% CI 1.41 to 1.68). In a separate model, smoking and unhealthy alcohol use conferred a greater AECOPD risk in veterans with HIV than in those without HIV (current smoking IRR 2.86 with HIV and 2.22 without HIV, past smoking IRR 1.78 with HIV and 1.62 without HIV, unhealthy alcohol use IRR 1.75 with HIV and 1.39 without HIV).

The VACS investigators conclude, "[S]everity of immune suppression increases risk for AECOPD, likely through greater risk of infection." They stress that two modifiable risk factors -- smoking and unhealthy alcohol use -- also independently boost AECOPD risk, and those factors raise increase that risk more in people with than without HIV.