High prevalence of COPD at baseline in START study sub-study

Gareth Hardy, HIV i-Base

Chronic obstructive pulmonary disease (COPD) has been a leading cause of death globally (currently third highest) for at least the last 25 years. The main risk factor for COPD is cigarette smoking.

Although observational studies have reported that HIV infection is an independent risk factor for COPD, these have generally been in small European or North American cohorts.

At AIDS 2014, Ken Kunisaki and colleagues at Minneapolis Veterans Administration Health Care System, Minnesota, presented baseline lung-function results from the pulmonary substudy of the ongoing international START study, reporting prevalence of COPD by region, age and smoking status. [1]

COPD is characterised by destruction of lung tissue (emphysema), airway inflammation and airway fibrosis. Airways become collapsible and narrowed, trapping air in the lung, hyperinflating the chest and leading to shortness of breath with exertion.

The substudy recruited 1027 treatment-naive adults from 20 countries. Enrolment by regions included United States (91), Asia (103), Latin America (191), Europe, Israel, Australia (313), and Africa (328). Other baseline characteristics included 29% women, 38% black and 34% white.

Due to the nature of the main study, median CD4 count was high (648 cells/mm3; IQR 582, 767) and people were in relatively early infection (HIV diagnosed for median 1.2 years (IQR 0.4, 3.5).

Approximately a third were current smokers (29%) and 11% were former smokers. Median age was 36 (IQR 30, 44) with entry criteria for the substudy being older than 25.

Lung function was assessed using standardised spirometry with COPD defined as FEV1/FVC ratio (forced expiratory volume in 1 second/forced vital capacity) below the predicted 5th percentile.

Overall, COPD was present in 6.8% of the cohort (95% CI: 5.3% – 8.5%), varying by region, with a strong association with current smoking and age. Prevalence was 12% in current smokers compared to 5% in former and 6% in never smoked.

However, almost half of those with COPD (47%) reported never smoked. COPD prevalence was 92% in those aged >44 compared to 4% in those under 30. Prevalence was 9.1% in Europe, Israel and Australia, 8.2% in the USA, 7.8% in Africa, 3.3% in Latin America and 2% in Asia.

In multivariate analysis with FEV1/FVC ratio as the dependent variable, COPD was more strongly associated with older age (p<0.0001) and increased smoking pack-years (p<0.0001), and more weakly with region (p=0.01). Gender had no effect.

The researchers speculated that the variation in COPD according to region may result from non-smoking factors such as environmental exposure to biomass fuel use, or occupational exposure to dust and smoke. However, no data on these parameters was collected.

In conclusion, COPD was found to be common in this cross-sectional analysis of HIV positive adults in early HIV infection, especially among smokers and older adults.

The researchers stressed the importance of smoking cessation interventions in adults with HIV as COPD is likely to emerge as a major co-morbidity in this population. However, the observation that nearly half of those with COPD reported never smoking, suggests the need for further investigation of COPD incidence.

The main START study has randomised 4685 HIV positive people with CD4 counts >500 cells/mm3 to either immediate or deferred ART (when CD4 is 350) with a primary endpoint of serious events of death. Top-line results are expected by the end of 2016, the predicted time for reaching 213 endpoints. [2]


This substudy from START will produce the largest longitudinal dataset for incidence of COPD in HIV positive people and with randomised data on the role of ART.

A second cross-sectional study was also just presented at ICAAC 2014, reporting 9% prevalence of COPD in 623 patients attending a single site in France. In this study, age and smoking history increased the risk of COPD (OR 1.61 [95%CI: 1.14-2.28] and 1.28 [95%CI: 1.09-1.50], respectively). Notably, COPD was previously undiagnosed in 77% of cases. [3, 4]


  1. Kunisaki K et al. Chronic obstructive pulmonary disease (COPD) in a large international cohort of HIV-infected adults with CD4+ counts >500 cells/mm3. 20th International AIDS Conference (AIDS 2014), 20-25 July 2014, Melbourne. Oral abstract WEAB0104. (abstract) (webcast)
  2. DSMB report for the Strategic Timing of AntiRetroviral Treatment (START) study, May 2014.
  3. Risso K et al. Chronic obstructive pulmonary disease in a large cohort of HIV-Infected patients: prevalence and predictive factors. 54th ICAAC, September 5-9, 2014. Washington, DC. Abstract H1196.
  4. Smart T. COPD may be common and underdiagnosed in people living with HIV. (12 September 2014).

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