Risk of cancers during interrupted antiretroviral therapy in the SMART study.
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.


METHODS
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/microl and (re)started if it fell to less than 250 cells/microl 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.


CONCLUSIONS
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.
Silverberg
Michael J
MJ
Division of Research, Kaiser Permanente Northern California, Oakland, California 94110, USA.
Neuhaus
Jacqueline
J
Bower
Mark
M
Gey
Daniela
D
Hatzakis
Angelos
A
Henry
Keith
K
Hidalgo
Jose
J
Lourtau
Leonardo
L
Neaton
James D
JD
Tambussi
Giuseppe
G
Abrams
Donald I
DI
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology; D008223:Lymphoma / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000209:etiology; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000453:epidemiology / Q000209:etiology; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology
D044966:Anti-Retroviral Agents; D012367:RNA, Viral