Infection with HIV is an independent risk
factor for lung cancer, according to the results of a large US study published
in the online edition of AIDS.
Investigators from the US Department of
Veterans Affairs found that HIV increased the relative risk of lung cancer by
70%, even after controlling for other potential risk factors.
“We found that HIV infected Veterans had a
significantly higher incidence of lung cancer than uninfected Veterans,” write
the authors. “HIV infection was an independent risk factor for lung cancer
after controlling for potential confounders including smoking.”
Although it is rare, lung cancer is an
increasingly important cause of death in patients with HIV. The exact reasons
for this are unclear. The immune damage caused by the virus may have an
important role. Moreover, it is well known that there is a high prevalence of
smoking among HIV-positive people. In addition, the intensive medical
monitoring that should form an integral part of HIV care could mean that lung cancer
is more likely to be detected in people with HIV than in uninfected
Investigators from the Department of
Veterans Affairs – a major provider of free HIV care in the US – wanted to
establish a clearer understanding of the possible association of HIV with this
They therefore studied data from 37,294
HIV-positive individuals, which was matched with the medical records of 75,750
HIV-negative people. The participants all received care after the introduction of
effective antiretroviral therapy. The investigators calculated the incidence of
lung cancer for the two groups, and also undertook a series of analyses to see
if HIV was an independent risk factor for the malignancy. These analyses took
into account other possible risk factors, such as age, gender, smoking and
history of other lung diseases.
Median duration of follow-up was 5.8 years
for the HIV-positive people and 7.3 years for the HIV-negative individuals (p
The patients had a mean age of 46 years and
98% were men. Approximately half were black.
The HIV-infected participants were more
likely to be current smokers (48 vs 46%), to misuse drugs (19 vs 13%) or
alcohol (16 vs 15%), to be co-infected with hepatitis C (35 vs 15%) and to have a
previous history of bacterial pneumonia (5 vs 1%; all comparisons, p <
A total of 457 new cases of lung cancer
were identified in the HIV-positive patients and 614 cases among the
HIV-negative individuals. The incidence of the malignancy was therefore 204
cases per 100,000 person-years for the HIV-infected patients and 119 cases per
100,000 person-years for the HIV-negative people in the control group. Incidence was therefore
some 70% higher in the HIV-positive
participants (IRR = 1.7; 95% CI, 1.5-2.0).
Next, the investigators compared the
characteristics of the HIV-positive and HIV-negative participants who developed
lung cancer. They found that those with HIV were older (51 vs 45 years),
were more likely to be white (47 vs 38%), had a higher prevalence of current
smokers (57 vs 48%), had increased rates of chronic obstructive pulmonary
disease (11 vs 4%) and were also more likely to have a been diagnosed with bacterial
pneumonia (8 vs 5%; comparisons, p < 0.001 or p = 0.01).
After taking into account other factors
associated with lung cancer risk, the investigators found that HIV remained a
significant, independent risk factor for the malignancy (IRR = 1.7; 95% CI,
1.5-1.9, p < 0.001).
Other risk factors included older age,
being a current or former smoker, having a history of chronic obstructive lung disease
(all p < 0.001), and a history of bacterial pneumonia (p = 0.007).
Sensitivity analyses, one of which
purposefully over-estimated the prevalence of HIV-positive participants who were
current smokers, confirmed the significant association between infection with
HIV and an increased risk of lung cancer (IRR = 1.2; 95% CI, 1.1-1.4).
Cancer stage at the time of diagnosis was
similar for the HIV-positive and HIV-negative participants. “The increased
incidence of lung cancer among the HIV infected patients does not appear to be
explained by more vigilant surveillance,” comment the investigators.
Although they found no significant
association between lung cancer risk and current CD4 cell count or viral load,
the researchers note that such associations have been found in other studies.
They write: “For the purposes of understanding the relationship between
immunodeficiency and lung cancer risk among HIV infected patients, we plan to
conduct more sophisticated analyses with time-updated modeling of CD4 cell
The authors believe their findings may
actually under-represent both the incidence and risk of lung cancer for
patients with HIV. They therefore conclude: “Additional investigations are
required to understand the mechanisms by which HIV infection may increase the
risk for lung cancer.”