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Risk of cancers during interrupted antiretroviral therapy in the SMART study

Silverberg, Michael Ja; Neuhaus, Jacquelineb; Bower, Markc; Gey, Danielad; Hatzakis, Angelose; Henry, Keithf; Hidalgo, Joseg; Lourtau, Leonardoh; Neaton, James Db; Tambussi, Giuseppei; Abrams, Donald Ij

doi: 10.1097/QAD.0b013e3282ed6338
Epidemiology and Social

Objective: To compare rates of AIDS-defining and non-AIDS-defining malignancies between patients on a CD4 T-cell-guided antiretroviral therapy (ART) strategy and continuous ART.

Design: A randomized clinical trial.

Methods: Malignancy rates were compared between the drug conservation arm in which ART was stopped if the CD4 T-cell count exceeded 350 cells/μl and (re)started if it fell to less than 250 cells/μl and the viral suppression arm utilizing continuous ART. Cox models were used to examine baseline characteristics including age, sex, race, cigarette use, previous malignancies, CD4 T-cell and HIV-RNA levels, hepatitis B or C, and ART duration.

Results: A total of 5472 participants were randomly assigned to treatment groups, of whom 70 developed cancer: 13 AIDS-defining malignancies and 58 non-AIDS-defining malignancies (one patient had both). The AIDS-defining malignancy rate per 1000 person-years was higher in the drug conservation arm (3.0 versus 0.5). Proximal CD4 T-cell and HIV RNA levels mediated much of this increased risk. The drug conservation arm also had higher rates of Kaposi's sarcoma (1.9 versus 0.3) and lymphoma (Hodgkin's and non-Hodgkin's; 1.1 versus 0.3). The non-AIDS-defining malignancy rate was similar between the drug conservation and viral suppression arms (8.8 versus 7.1). The most common non-AIDS-defining malignancies were skin (n = 16), lung (n = 8) and prostate (n = 6) cancers.

Conclusion: Non-AIDS-defining malignancies were more common in this cohort than AIDS-defining malignancies. This analysis provides further evidence against the use of CD4 T-cell-guided ART because of a higher risk of AIDS-defining malignancies in addition to opportunistic infections and deaths.

From the aDivision of Research, Kaiser Permanente Northern California, Oakland, California, USA

bDivision of Biostatistics, University of Minnesota, School of Public Health, Minneapolis, Minnesota, USA

cDepartments of Oncology and HIV Medicine, Chelsea and Westminster Hospital, London, UK

dCopenhagen HIV Programme, Faculty of Health Sciences, University of Copenhagen, Panum Institute, Copenhagen, Denmark

eDepartment of Hygiene and Epidemiology, Athens University Medical School, Athens, Greece

fHIV Program, Minnesota AIDS Clinical Trials Unit, Minneapolis, Minnesota, USA

gHIV Program, Guillermo Almenara Hospital, Lima, Peru

hServicio de Inmunocomprometidos, Hospital JM Ramos Mejía, Buenos Aires, Argentina

iClinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy

jHematology–Oncology Division, San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA.

Received 24 April, 2007

Revised 7 June, 2007

Accepted 14 June, 2007

Correspondence to Donald I. Abrams, MD, Hematology–Oncology Division, San Francisco General Hospital, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110-2859, USA. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.