Risk of cancers during interrupted antiretroviral therapy in the SMART study

Michael J. Silverberg, Jacqueline Neuhaus, Mark Bower, Daniela Gey, Angelos Hatzakis, Keith Henry, Jose Hidalgo, Leonardo Lourtau, James D. Neaton, Giuseppe Tambussi, Donald I. Abrams

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1957-1963
Number of pages7
Issue number14
StatePublished - Sep 2007


  • Antiretroviral therapy
  • CD4 T-cell counts
  • Cancer
  • HIV
  • Randomized clinical trials


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