People with detectable HIV viral load and advanced immune
deficiency are likely to experience greater decreases in lung function over
time, with high viral load linked to more impairment than smoking, according to
a study presented last week at the 19th Conference
on Retroviruses and Opportunistic Infections in Seattle.
Speaking at a
session on metabolic and cardiovascular complications associated with HIV and
its treatment, Michael Drummond from Johns Hopkins University described an
analysis of lung function changes among participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study.
Drummond's team previously reported that a cross-sectional
analysis -- looking across all patients at a single point in time -- showed
that higher HIV RNA levels were associated with increased risk of obstructive
lung disease. This category includes lung problems characterised
by inflamed airways and shortness of breath, for example asthma and chronic
obstructive pulmonary disease (COPD); it
does not include infectious illnesses traditionally associated with HIV/AIDS
such as Pneumocystis pneumonia or
In this study the researchers looked at longitudinal data,
analysing changes in lung function over time. The analysis included 1,064
injection drug users in Baltimore, one-third of whom were HIV-positive.
A majority of participants (65%) were men, the average age
was 49 years, and about 90% were black. The HIV-positive group as a whole did
not have well-controlled disease, with only 55% on antiretroviral therapy (ART)
and 10% having high viral load (>75,000 copies/mL). Almost all (95%)
had a history of tobacco smoking, with 88% being current smokers.
Over a median 2.75 years of follow-up, the researchers
performed 455 spirometry measurements, a lung
function test that measures the volume or flow of air as it is inhaled and
exhaled. They then estimated the effects
of HIV infection, viral load and CD4 T-cell count on annual changes in forced
expiration volume in one second, known as FEV1; FEV1 levels below 25% of normal
are generally disabling.
At baseline, 16% of participants had obstructive lung
disease and the overall prevalence did not differ significantly between HIV-positive
and HIV-negative people. People with HIV did, however, have lower FEV1 at
baseline after adjusting for demographic factors, body mass index and smoking.
Overall, HIV-positive people did not experience
significantly faster decline of FEV1 compared with HIV-negative people (-23.7
vs -35.7 mL/year, respectively).
But HIV-positive people with viral load above 75,000
copies/mL did show significantly greater annual decline in FEV1 (-99.1
mL/year), compared with -29.9 mL/year for those with lower HIV RNA levels.
Similarly, while HIV-positive people with CD4 T-cell counts
above 200 cells/mm3 had rates of FEV1 decline similar to those of
HIV-negative people (-26.3 mL/year), people with CD4 counts of 100-200 cells/mm3
or below 100 cells/mm3 experienced significantly more rapid
FEV1 decline (-57.9 and -80.0 mL/year, respectively).
Based on these findings the researchers concluded,
"Markers of advanced and uncontrolled HIV disease are associated with more
rapid decline in lung function." This decline was "statistically and probably clinically significant
as well," Drummond added.
Drummond explained that lung function typically declines
slowly with age. Among smokers the decline is larger and more rapid, in the
range of -50 to -70 mL/year. In this study, people with uncontrolled HIV and
advanced immune deficiency had even greater declines than smokers.
It was difficult to make comparisons between smokers and
non-smokers in this study because most participants smoked now or in the past.
Drummond said his team did not see an effect of smoking marijuana or using
other illegal drugs.
Drummond's team suggested that, "Optimal antiretroviral
therapy with HIV virological suppression may diminish accelerated lung function
decline." The study also underscores the importance of smoking cessation
counseling and support.
Drummond said it appears that viral load is the main driver
of the decline in lung function, and proposed this might be related to
accelerated apoptosis (programmed cell death) or systemic inflammation. This study
adds to the growing evidence linking inflammation and age-related non-AIDS
conditions in people with HIV.