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Research Alert: Study Casts Doubt on "Shock and Kill" Cure Strategy

Incidence of Cancers in Australian Observational Cohort

May/June 2013

An Australian prospective cohort study described the incidence of AIDS-defining cancers (ADC), non AIDS-defining cancers (NADC) and all cancers from 1992-2005 reporting a strong negative association with CD4 cell count. Other HIV related factors such as prior AIDS, ART and HIV viral load were closely linked to ADCs.

This study, from Kathy Petoumenous and colleagues, was published in the February 2013 edition of HIV Medicine. This was a prospective cohort study of HIV related factors and the rate of cancer incidence from the onset of HIV diagnosis. The study included 2181 patients from the Australian HIV Observational Database (AHOD).

Cancer diagnosis was established using data from the Australian Cancer database (ACD) and the Australian National HIV database (NHD) and the National AIDs Registry (NAR). The databases were matched by a two by two name code and then AHOD was matched to the NHD and NAR records. All invasive cancers were included with the exception of nonmelanoma skin cancer.1

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ADCs were Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and cervical cancers. All other cancers were classified as NADCs. Each incident cancer was also categorized as infection-related (IR) or non-infection related (NIR). IR cancers observed in the study were Epstein-Barr virus (Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL) and nasopharynx cancer), human herpes virus 8 (HHV-8) and HPV (cervix, vagina, penis, anus, oral cavity and pharynx cavity).

Limited information on baseline characteristics were provided, although this have been published in other papers.1

The study identified 139 linked cancers (n=129) out of the 2181 AHOD participants. All but one of the cancers was diagnosed in male patients. The majority of all cancers were infection related (78%). Eighty-eight cancers (63%) were ADC, 61 (69%) were KS and 27 (31%) were NHL. The most common cancers among NADCs were melanoma (n=10), lung cancer (n=6), HL (n=5) and anal cancer (n=5).

The median age for cancer diagnosis was 43 years (IQR: 37-52). Median age of ADCs cancer diagnosis was lower compared to NADCs at median 41 years (IQR: 36-49) and 50 years (IQR 39-56) respectively.

Among the 2181 AHOD patients, 1793 had a recorded date of HIV diagnosis and 107 out of the 129 diagnosed with cancer had a recorded date of HIV diagnosis. Among these cancer patients there was a total of 21,021 person years (PY) of follow-up since the date of HIV diagnosis. This gave an overall crude rate of cancer incidence of 5.09/1000 PY. Cancer incidence rate for all cancers was greatest during the period of 1993-1996 (5.4/100 PY; 95% CI 3.54-8.05/1000 PY) and for KS (92.85/1000 PY; 95% CI 1.51-4.83/1000 PY). All cancers do not include KS, NHL and NADCs numbers.

At a CD4 cell count <100 cells/mm3, the incidence rate (/1000 PY) for all cancers was at its highest 15.9 (95% CI 9.25-25.4) compared to 2.0 (95% CI 1.15-3.17) for CD4 cell count >500 cells/mm3. A trend observed in both ADCs and NADCs.

In multivariate analysis CD4 cell count was again the strongest risk factor for the incidence of ADC and non-ADCs. At CD4 cell count <100 cells/mm3 the incidence rate ratio (IRR /1000 PY) of ADC was 4.32 (95% CI 1.95-9.57), p<0.001. People on ART had a lower risk factor for ADCs [IRR of 0.45 (95% CI 0.28-0.74), p=0.002]. Prior AIDS was a strong determining risk factor [IRR 3.98; (95%CI 2.39-6.62), p=0.001].

For NADCs CD4 cell count 100-199 cells/mm3 [IRR 3.49 (CI 95% 1.48-8.22), p=0.004] and prior AIDs [IRR 2.63 (CI 95% 1.37-5.06), p=0.004] were the two biggest risk factors. Patient numbers were too low to calculate the IRR of ART as a risk factor.

Age was a risk factor for ADCs and NADCs [IRR 1.14 (CI 95% 1.01-1.21), p=0.039] and [IRR 2.63 (CI 95% 1.37-5.06), p<0.001].

From 2000 onwards the rate of cancer incidence was much greater in NADCs [2.15; 95% CI 1.37-3.31] compared to KS [1.62; 95% CI 95% 0.92-2.62].


References

  1. Petoumenos K et al. Cancer, immunodeficiency and antiretroviral treatment: results from the Australian HIV Observational Database (AHOD). HIV Med. 2013 Feb 14(2):77-84. doi: 10.1111/j.1468-1293.2012.01038.x.
  2. The Australian HIV Observational Database. Rates of combination antiretroviral treatment change in Australia, 1997-2000. HIV Med. 2002 Jan 3(1): 28-36.

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