A large US study has provided important new
insights into the incidence and timing of cancers among people taking
antiretroviral therapy. Published in the online edition of Clinical Infectious Diseases, the study showed that incidence of
AIDS-defining cancers was highest in the six months after starting HIV
therapy and then fell dramatically.
In contrast, after the first year of HIV
treatment, annual rates of non-AIDS defining cancers increased by approximately
7%, an increase attributed to ageing. A lower CD4 cell count at the time
antiretroviral treatment was started was a risk factor for several cancers.
The investigators believe their findings
show the importance of early antiretroviral therapy and the integration of "aggressive" cancer screening into routine HIV care.
Cancers are an important cause of serious
illness and death in people living with HIV. However, the timing and incidence of
malignancies after starting antiretroviral therapy has received little
A team of investigators in the United
States therefore examined the records of approximately 11,500 people who
started triple-drug HIV therapy between 1996 and 2011. Trends in cancer
incidence were monitored for up to ten years after treatment initiation. The
investigators also sought to identify factors associated with a cancer
The investigators divided cancers into
several categories: AIDS-defining cancers (Kaposi’s sarcoma, non-Hodgkin’s
lymphoma and cervical cancer); non-AIDS-defining cancers; lymphomas;
cancers related to human papillomavirus (HPV); other virus-related cancers; and virus-unrelated cancers.
The patients were racially diverse and
overwhelmingly male (80%). The median age for starting antiretroviral
therapy was 38 years. Most people were immunosuppressed when they started
treatment, median CD4 cell count being just 202 cells/mm3. The
majority of people (47%) started treatment with a regimen based on a protease
inhibitor and 42% started treatment with a non-nucleoside reverse transcriptase
inhibitor (NNRTI)-based combination.
Patients were followed for a median of
three years and 10% of patients contributed ten years of follow-up.
There were 457 cancer diagnoses during
46,318 person-years of follow-up.
This provided an incidence rate of 987
cases per 100,000 person-years.
Overall incidence of AIDS-defining cancers
was similar to the incidence rate for non-AIDS-defining cancers (515 vs 466
per 100,000 person-years).
Kaposi’s sarcoma was the most common
AIDS-defining cancer, with an incidence rate of 304 cases per 100,000
person-years. The most common non-AIDS-defining malignancy was anal cancer (69
cases per 100,000 person-years). Among women, the most common non-AIDS cancer
was breast cancer (128 cases per 100,000 person-years).
The timing of cancer diagnosis varied
according to whether the malignancy was AIDS-defining or non-HIV-related.
Incidence of Kaposi’s sarcoma was
especially high in the first six months after HIV therapy was started (1342
cases per 100,000 person-years). Incidence then fell dramatically during the
second six months of therapy (348 cases per 100,000 person-years). Incidence of
the cancer then remained at low rates throughout the rest of follow-up (164
cases per 100,000 person-years).
A similar trend was observed for lymphomas
(both non-Hodgkin and Hodgkin). Incidence was highest in the first six months
after treatment initiation (660 cases per 100,000 person-years) and then fell
sharply in the next six months (269 cases per 100,000 person-years).
In contrast, incidence of all
non-AIDS-defining cancers increased with longer duration of follow-up. The increase
was 7% for each additional year of treatment. Incidence climbed from 416 cases
per 100,000 person-years after the first year of therapy to 615 cases per
100,000 person-years after ten years of treatment.
"This increase is likely a consequence of
increasing cancer incidence with advancing age, as noted in the general
population", write the authors.
Each ten-year increase in age was
associated with a doubling in the risk of non-lymphoma cancers and HPV-related
cancers (adjusted HR = 2.33; 95% CI, 1.97-2.74).
CD4 cell count at the time HIV therapy was
started was also associated with subsequent cancer risk.
Immune suppression at the time of treatment
initiation was an especially strong predictor of Kaposi’s sarcoma. The pattern
of a high incidence of this malignancy in the first six months of treatment
followed by a steep decline was seen only in people with a baseline CD4 cell
count below 200 cells/mm3 (p = 0.002). People with a CD4 cell
count above this level when they started therapy had a low incidence of
Kaposi’s sarcoma throughout follow-up.
A low CD4 cell count was also associated
with the development of lymphomas and diagnosis with HPV-related cancers.
The investigators found no evidence that
overall cancer incidence declined over time, therefore suggesting "incremental
improvements in antiretroviral therapy during the modern antiretroviral therapy
era have not had dramatic effects on cancer incidence". They believe this
finding "emphasizes the continued need for cancer screening and prevention
measures in the HIV population…for instance increased HPV vaccination and anal
pap smear screening may help prevent anal cancer, one of the most common
malignancies in this population."
The authors also believe their study
further supports efforts to reduce rates of late HIV diagnosis.