A poor CD4
response to antiretroviral therapy (ART) is associated with an increased risk
of virus-related non-AIDS-defining cancers (NADC), US investigators report in AIDS. Several CD4 count measures were
associated with this risk, all were independent of baseline immune status,
viral load and age.
recommend that people living with HIV who have low CD4 counts should be intensively screened for
virus-related malignancies. The most frequently-occurring virus-related malignancies are those caused by human papillomavirus (anal cancer and squamous cell cancers of the oral cavity and pharynx), hepatitis B and C (liver cancer) and Epstein-Barr virus (Hodgkin lymphoma).
effects of immune status at ART initiation, changes in immune status after ART
initiation impact on virus-related NADC risk with the influence of early CD4+
cell response being most notable,” comment the authors. “This highlights the
importance of adherence to effective durable ART to reduce the risk of
virus-associated cancers in a population at increased risk for repeated
episodes of infection with oncogenic viruses.”
treatment and care mean that many people living with HIV now have a normal life
expectancy. However, non-AIDS-defining cancers such as lung cancer, anal cancer
and Hodgkin’s lymphoma remain more common in people living with HIV compared to
the general population. The reasons for this include high rates of smoking and
sexual risk behaviour. The immune suppression associated with HIV infection may
also have a role.
wanted to see if CD4 cell response to HIV therapy was associated with the risk
of non-AIDS-defining cancers.
population comprised 9389 people who started HIV therapy between 1996 and
2011. The authors examined the association between the risk of diagnosis with
non-AIDS-defining cancers and CD4 count six months after starting treatment,
latest CD4 count and cumulative CD4 count. This final variable was a measure of
the magnitude and durability of immune response to treatment.
categorised as virus related and non-virus related.
Median CD4 count
and viral load at treatment initiation was 200 cells/mm3 and 63,000
copies/ml, respectively. A fifth of the patients were women, 43% were white and
the median age at baseline was 38 years. Six months after treatment initiation,
64% of patients had an undetectable viral load.
After the first
six months of therapy, patients were followed for a median of an additional 3.3
years and contributed a total of 41,538 person-years of follow-up.
a mean of nine CD4 count measurements. Median CD4 count during the first six
months of treatment was 260 cells/mm3, increasing to 324 cells/mm3
in the second six months and 358 cells/mm3 between months 12 and
18. The pace of CD4 gain then slowed.
cumulative CD4 count showed that the average count during the first five years
of follow-up was 385 cells/mm3, increasing to 457 cells/mm3
over ten years.
A total of 164
non-AIDS-defining cancers were diagnosed, giving an incidence rate of 395 per
100,000 person years. Sixty-five cancers (40%) were virus related, the most
frequent being anal cancer (n = 26).
Each 100 cells/mm3
increase in six-month CD4 count decreased the risk of diagnosis with a
virus-related non-AIDS-defining cancer by 29% (HR = 0.71; 95% CI, 5.0-47.0).
Similarly, each 100 cell/mm3 increase in current CD4 count decreased
the risk of diagnosis with this category of cancer by 30% (HR = 0.70; 95% CI,
7-48). Higher cumulative viral load was also associated with a decreased risk
of virus-related non-AIDS malignancies.
were little altered when the authors limited their analysis to the 73% of
patients who were taking their first antiretroviral regimen.
There was no
association between immune response to therapy and the risk of
“A greater CD4+
cell count ART response was associated with a lower NADC incidence,
specifically for NADCs related to viral coinfections,” write the authors. “The
association was independent of CD4+cell count at ART initiation,
HIV-1 RNA response, age and other patient factors and consistently observed for
measures of early, time-varying and cumulative time-varying immunologic ART
believe that the long-term magnitude and durability of CD4 response “may be
particularly relevant to virus-related NADCs, as longer periods of
immunosuppression may provide greater susceptibility to acquisition, reactivation
or persistence of oncogenic viruses.”
They recommend people with low CD4 counts during HIV therapy should have frequent screens
for virus-related malignancies.