TY - JOUR
T1 - Risk of cancers during interrupted antiretroviral therapy in the SMART study
AU - Silverberg, Michael J.
AU - Neuhaus, Jacqueline
AU - Bower, Mark
AU - Gey, Daniela
AU - Hatzakis, Angelos
AU - Henry, Keith
AU - Hidalgo, Jose
AU - Lourtau, Leonardo
AU - Neaton, James D.
AU - Tambussi, Giuseppe
AU - Abrams, Donald I.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Antiretroviral therapy
KW - CD4 T-cell counts
KW - Cancer
KW - HIV
KW - Randomized clinical trials
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U2 - 10.1097/QAD.0b013e3282ed6338
DO - 10.1097/QAD.0b013e3282ed6338
M3 - Article
C2 - 17721103
AN - SCOPUS:34548222243
SN - 0269-9370
VL - 21
SP - 1957
EP - 1963
JO - AIDS
JF - AIDS
IS - 14
ER -