Low CD4 count, smoking and unhealthy alcohol use are risk factors for acute exacerbation of COPD in people with HIV

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HIV infection increases the risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), investigators from the US Department of Veterans Affairs report in the online edition of AIDS. A low CD4 cell count was a significant risk factor, and HIV infection amplified the already well-established association between AECOPD and smoking and problematic alcohol use.

“We found that HIV was independently associated with an increased risk of AECOPD, and that immune suppression, reflected by a lower baseline CD4+ cell count, was associated with a greater risk of AECOPD,” comment the authors. They add, “the increased risk of AECOPD in HIV may be related to enhanced susceptibility to harms from the modifiable risk factors of smoking and unhealthy alcohol use.”

Chronic obstructive pulmonary disease (COPD) affects approximately 7% of the US population, causing significant illness and death. The disease is associated with annual healthcare costs in the region of $60-70 billion.


chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Symptoms include difficulty breathing, cough, mucus (sputum) production and wheezing. It is caused by long-term exposure to irritating gases or particulate matter, most often from tobacco smoking (active or passive).


Affecting the lungs.


acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

disease progression

The worsening of a disease.



HIV is now a manageable condition and many patients are surviving well into old age. Previous research has shown an increased prevalence of COPD among patients with HIV, even after controlling for well-known risk factors, such as smoking.

Investigators wanted to see if patients with HIV were also at risk of acute exacerbation of COPD. They therefore designed a study comparing incidence rates over two years between HIV-positive patients and HIV-negative individuals enrolled in the Virtual Cohort of the Veterans Aging Cohort Study.

The authors hypothesized that incidence would indeed be higher among those with HIV, and that modifiable risk factors, such as low CD4 count, smoking and unhealthy alcohol use, would increase the risk of AECOPD.

A total of 43,618 HIV-positive and 86,492 HIV-negative individuals were enrolled in the study. Approximately 4% of patients had a diagnosis of COPD at baseline. AECOPD was defined as an inpatient or outpatient diagnosis of the condition accompanied by a steroid and/or antibiotic prescription within five days.

Patients were followed for 234,099 person-years. During this time, 1428 HIV-positive and 2104 HIV-negative patients had one or more diagnoses of AECOPD. Half the patients with AECOPD had a baseline COPD diagnosis.

The rate of AECOPD was significantly higher among patients with HIV compared to uninfected individuals (19% vs. 13%, p < 0.001). 

Among patients with HIV, a decreasing CD4 count was associated with an increased risk of AECOPD (below 200 cells/mm3, IRR = 2.12; 95% CI, 1.86-2.42; 200-349 cells/mm3, IRR =1.31; 95% CI, 1.11-1.54). In contrast, use of antiretroviral therapy was protective against diagnosis with AECOPD.

Overall, HIV infection increased the risk of AECOPD by approximately half (IRR = 1.54; 95% CI, 1.44-1.65).

When compared with HIV-negative patients, individuals with a CD4 count below 200 cells/mm3  (IRR = 2.30; 95% CI, 2.10-2.53) and between 200-349 cells/mm3, (IRR = 1.32; 95% CI, 1.15-1.51) had an especially high risk of AECOPD. Conversely, HIV-positive patients with higher CD4 counts did not have a significantly increased risk of COPD progression when compared to HIV-negative individuals.

Current and past smoking and alcohol-related diagnoses were risk factors for AECOPD across the cohort.

However, HIV amplified the association between disease progression and current smoking (IRR = 1.18; 95% CI, 1.03-1.35, p = 0.021) and alcohol-related problems (IRR = 1.22; 95% CI, 1.04-1.44, p = 0.017).

“Modifiable risk factors to target in future trials to decrease AECOPD in HIV-infected patients include current smoking and unhealthy alcohol use,” conclude the investigators. “Intervening on these contributing factors may decrease morbidity and costs associated with COPD particularly in a vulnerable HIV-infected population.”


Depp TB et al. Risk factors associated with acute exacerbation of chronic obstructive pulmonary disease in HIV-infected and uninfected patients. AIDS 29, online edition. DOI: 10.1097/QAD.0000000000000940 (2015).