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Faster Lung Function Decline With HIV Linked to sCD14 Activation Marker
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Spirometry-measured lung function fell faster in HIV-positive people than in a matched HIV-negative group in a 2009-2012 study [1]. Soluble CD14 (sCD14), an immune activation marker, predicted faster lung function decline in people with HIV, but not in the HIV-negative comparison group.
Compared with the general population, people with HIV have higher rates of chronic obstructive pulmonary disease (COPD), noted researchers from the University of Washington, Seattle. People with COPD and current smokers have about a 60-mL/year drop in forced expiratory volume in 1 second (FEV1), compared with about 30 mL/year in healthy nonsmokers. Previous research, the Seattle team observed, links low CD4 count and high viral load in injection drug users to faster FEV1 drops [2]. But the impact of HIV-associated chronic inflammation, immune activation, and altered coagulation on lung disease remains unexplored.
To address these issues, the University of Washington group compared FEV1 over time in HIV-positive and negative outpatients of the Veterans Aging Cohort Study (VACS), matching the groups for current smoking. Study participants enrolled from 2009 through 2012 and had postbronchodilator spirometry at the baseline visit then every 6 to 12 months, averaging three spirometry measures per person over 24 months. The investigators collected samples to measure IL-6 (an inflammation marker), sCD14 (an activation marker), and d-dimer (a coagulation marker).
Median ages of the 168 HIV-positive people and 147 HIV-negative controls were 55 and 53 (P < 0.05). Large majorities of people with and without HIV (98% and 88%) were men (P < 0.05), and about two thirds were black (69% and 63%). Proportions of current smokers were 64% with HIV and 57% without HIV (a nonsignificant difference), while proportions of injection drug users were 33% and 17% (P < 0.05). Most people with HIV, 91%, were taking antiretroviral therapy. Median CD4 count and viral load in the HIV group stood at 431 and 48 copies.
Median levels of two of the three markers assessed were significantly higher in the HIV group: IL-6 (1.88 versus 1.44 pg/mL) and sCD14 (1666 versus 1413 ng/mL) (P < 0.05 for both). Median d-dimer levels were significantly lower in the HIV group (0.26 versus 0.28 mcg/mL, P < 0.05).
People with HIV had higher baseline forced vital capacity (FVC, average 96 versus 92, P < 0.05), but not when calculated as percent predicted (16% and 16%). Average baseline FEV1 was similar in the HIV and non-HIV groups (average 92 and 89, percent predicted 19% and 17%). Airflow obstruction, defined as FEV1/FVC below 70%, did not differ significantly between the two groups at the baseline visit (20% versus 18%). But a significantly higher proportion of people with than without HIV had diffusing capacity below 60% predicted (40% versus 25%, P < 0.05).
In a generalized estimating equation model adjusted for age, body mass index, and smoking pack-years, FEV1 declined significantly more over time in the HIV group than in HIV-negative controls, 100 versus 63 mL/year (P = 0.03). An analysis adjusted for CD4 count, viral load, race/ethnicity, smoking pack-years, and injection drug use found associations between higher levels of all three biomarkers and worse baseline FEV1 percent in people with HIV but not in those without HIV.
A generalized estimating equation model adjusted for age, body mass index, and pack-years linked higher sCD14 levels with faster FEV1 decline in people with HIV (110 mL/year with sCD14 above group median versus 56 mL/year with sCD4 below median, P < 0.01). This association did not hold true for people without HIV. And FEV1 decline did not differ significantly by IL-6 or d-dimer level in either group.
The link between higher sCD14 and declining lung function, the researchers conclude, suggests that "selective innate immune activation may play an important role in the progression of COPD in HIV infection." Although rapid drops in FEV1 are linked to worsening health in the general population, the Seattle team noted that the clinical impact of falling FEV1 requires further study in people with HIV.
References
1. Crothers K, Rodriguez CV, Wongtrakool C, et al. Association of HIV infection and immune activation with decline in lung function. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 774.
2. Drummond MB, Merlo CA, Astemborski J, et al. The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort. AIDS. 2013;27:1303-1311. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953568/
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