Duration of HIV Infection and Detectable Viral Load Linked to Higher Risk of Non-AIDS-defining
studies presented last week at the 5th International AIDS Society Conference on
HIV Pathogenesis, Treatment and Prevention (IAS 2009) add to the evidence linking
HIV infection, CD4 well decline, and cancer, even among people with relatively
well-preserved immune function, though results differed with regard to AIDS-defining
and non-AIDS-defining cancers.|
is well known that people with HIV are at higher risk for AIDS-defining cancers
such as Kaposi's sarcoma, but data
has accumulated in recent years indicating that HIV infection also raises
the risk of certain non-AIDS-defining malignancies, even at CD4 cell levels above
the traditional opportunistic infection "danger zone" of 200 cells/mm3.
Kesselring from the HIV Monitoring Foundation in Amsterdam and colleagues investigated
the association between immunodeficiency, HIV viremia, and non-AIDS defining malignancies,
while adjusting for traditional cancer risk factors.
investigators looked at 11,459 patients in the observational Netherlands ATHENA
cohort who started combination antiretroviral
therapy (ART) since January 1, 1996. A majority (77%) were men and the median
age was 38 years. Participants could be either treatment-naive or have previously
used nucleoside reverse transcriptase inhibitor (NRTI)
monotherapy or dual therapy. About one-quarter had a prior AIDS diagnosis, the
median nadir (lowest-ever) CD4 cell count was 150 cells/mm3, more than 70% had
ever smoked, and 5% each had hepatitis B virus (HBV)
and hepatitis C virus (HCV) coinfection.
researchers compared the risk of fatal and non-fatal non-AIDS-defining cancers
occurring after the start of combination ART (excluding basal cell and squamous
cell skin cancers), and their association with potential risk factors including
age, sex, region of origin, smoking, alcohol use, HBV and HCV coinfection, HIV
transmission route, prior AIDS diagnosis, nadir CD4 count, CD4 cell count and
viral load at the start of treatment, interval between HIV diagnosis and treatment,
and duration of ART. CD4 count and viral load were also considered as time-updated
variables and as a measure of cumulative time with a CD4 count below 200, 350,
or 500 cells/mm³ and with detectable HIV RNA > 400 cps/mL.
were classified as being non-infectious or related to infections including human
papillomavirus (HPV), which can cause cervical, anal, and oral cancers, and HBV
or HCV, which can cause liver cancer.
67,179 person-years (PY) of follow-up, a total of 232 malignancies were reported.|
were related to infections and 57% were due to other causes.|
most common types were lung cancer (44%), anal cancer (37%), and other epithelial
the 6 months prior to cancer diagnosis, 89% of affected patients were on combination
ART, 75% had undetectable HIV viral load, and the median CD4 count was 340 cells/mm3.|
duration with a CD4 count below 350 cells/mm³ was associated with development
of non-AIDS-defining malignancies.|
association was attributable to infection-related cancers.|
duration of detectable viral load, however, was not a significant risk factor.|
the setting of treated HIV infection, longer exposure to immunodeficiency below
350 CD4 cells/mm3 [is] associated with non-AIDS-defining malignancies," the
researchers concluded. "Longer exposure to viremia was not associated with
Monitoring Foundation, Amsterdam, Netherlands; Academic Medical Center of the
University of Amsterdam, Department of Infectious Diseases, Tropical Medicine
and AIDS, Amsterdam, Netherlands.
a related study, Nancy Crum-Cianflone from the Naval Medical Center San Diego
and colleagues asked what CD4 cell levels are associated with a reduced rate of
cancer in people with HIV.
investigators retrospectively analyzed 4963 participants from 7 sites enrolled
in a prospective, multicenter U.S. Military HIV Natural History Study between
1984 and 2008, representing 37,660 person-years. In this study, patients were
on average younger (median 28 years) and were more likely to men (92%).
too, malignancies were classified as AIDS-defining (Kaposis sarcoma, non-Hodgkins
lymphoma, or invasive cervical carcinoma) or non-AIDS-defining.
total of 501 patients (10.3%) developed cancer during the study period (including
20 with more than 1 type).|
were 336 AIDS-defining cancers and 186 non-AIDS-defining cancers.|
most common non-AIDS-defining cancer were skin cancers (52%), anal cancer (15%),
and Hodgkin?s disease (9%). |
who developed cancer and in particular an AIDS-defining cancer had a lower CD4
nadir before cancer developed and a lower CD4 count nearest the time of cancer
median CD4 count nearest the time of AIDS-defining cancer diagnosis was 53 cells/mm3,
compared with 454 cells/mm3 for non-AIDS-defining cancer diagnosis.|
the highest rate of AIDS-defining cancer was 44.7 per 1000 PY, observed in people
with CD4 counts < 200 cells/mm3. |
CD4 counts increased, the incidence of AIDS-defining cancer progressively declined,
with the lowest rate of 1.3 per 1000 PYs seen in people with a CD4 count >
700 cells/mm3. |
incidence of non-AIDS-defining cancers was similar in people with CD4 counts <
200 cells/mm3 and 500-700 cells/mm3 (5.1 and 5.6 per 1000 PY, respectively). |
rate fell to 3.6 per 1000 PY, however, for those with CD4 counts > 700 cells/mm3.
with the pre-HAART era, the rate of AIDS-defining cancer was lower in each CD4
cell strata after the advent of HAART.|
of non-AIDS-defining cancers, in contrast, were slightly higher in the HAART era.
of non-AIDS-defining cancers other than skin cancers were relatively similar across
CD4 cell strata, but skin cancers occurred at lower rates in people with >
the risk of AIDS-defining cancers was highest at CD4 counts < 200 cells/mm3,
increased risk was also present at counts < 500," the researchers concluded.
"There was an association between non-AIDS-defining cancers and CD4 counts
< 700 cells/mm3 during follow-up."
association was mainly seen in the pre-HAART era and for skin cancers: they continued.
"During the HAART era, there was no association between non-skin non-AIDS-defining
cancers and CD4 strata."
robust CD4 counts is useful in reducing AIDS-defining cancers among HIV patients,
but did not have a significant impact on non-AIDS-defining cancers in the HAART
Disease Clinical Research Program, Bethesda, MD; Naval Medical Center San Diego,
San Diego, CA; University of Minnesota, Minneapolis, MN.
Kesselring, L Gras, C Smit, and others. Immunodeficiency, not viremia, is a risk
factor for non-AIDS-defining malignancies in patients on cART. 5th International
AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009).
July 19-22, 2009. Cape Town, South Africa. Abstract
Crum-Cianflone, K Huppler Hullsiek, V Marconi, and others. What CD4 cell count
levels are associated with a reduced risk of cancer? 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22,
2009. Cape Town, South Africa. Abstract