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Originally published as JCO Early Release 10.1200/JCO.2008.19.6626 on December 29 2008

Journal of Clinical Oncology, Vol 27, No 6 (February 20), 2009: pp. 884-890
© 2009 American Society of Clinical Oncology.

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AIDS-Related Cancer

Highly Active Antiretroviral Therapy and the Incidence of Non–AIDS-Defining Cancers in People With HIV Infection

Thomas Powles, David Robinson, Justin Stebbing, Jonathan Shamash, Mark Nelson, Brian Gazzard, Sundhiya Mandelia, Henrik Møller, Mark Bower

From the Department of Medical Oncology, St Bartholomew's Hospital, Little Brittain; Department of Medical Statistics. Thames Cancer Registry; and the Department of Oncology, Chelsea and Westminster Hospital, London, United Kingdom.

Corresponding author: Thomas Powles MD, MRCP, Department of Medical Oncology, St Bartholomew's Hospital, Little Brittain, London EC1A7BE, United Kingdom; e-mail: thomas.powles{at}bartsandthelondon.nhs.uk.

Purpose The effect of highly active antiretroviral therapy (HAART) on the incidence of non–AIDS-defining cancers (NADCs) is unclear.

Methods We have investigated the occurrence of NADCs in a prospective cohort of 11,112 HIV-positive individuals, with 71,687 patient-years of follow-up. Standardized incidence ratios (SIRs) were calculated using general population incidence data. We investigated the effect of calendar period, HIV parameters, and immunologic and treatment-related factors on the incidence of these cancers using univariate and multivariate analyses.

Results The SIR for all NADCs was 1.96 (95% CI, 1.66 to 2.29). There was no significant excess in incidence in the pre-HAART era (1983 to 1995; SIR, 0.95; 95% CI, 0.58 to 1.47). However, the incidence increased in the early HAART period (1996 to 2001) and remains elevated in the most recent established HAART period (2002 to 2007; SIR, 2.05; 95% CI, 1.51 to 2.72, and SIR 2.49; 95% CI, 2.00 to 3.07, respectively). Multivariate analysis showed that use of HAART (hazard ratio [HR] = 1.64; 95% CI, 1.13 to 2.39) and a nadir CD4 count less than 200/µL (HR = 1.67; 95% CI, 1.10 to 2.54) were associated with an increased risk. Only the non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with a significantly increased risk of NADCs (HR = 1.45; 95% CI, 1.01 to 2.08). Much of this association was attributable to an increased risk of Hodgkin's lymphoma with NNRTIs (HR = 2.20; 95% CI, 1.03 to 4.69).

Conclusion Since the introduction of HAART, there has been a significantly increased risk of NADCs, which has now stabilized. A number of factors are associated with this increased risk, including HAART use. There may be an association between the use of NNRTIs and the development of Hodgkin's lymphoma.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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