Risk of cancers during interrupted antiretroviral therapy in the SMART study

• Published in: AIDS (London) Vol. 21; no. 14; pp. 1957 - 1963
• Main Authors: SILVERBERG, Michael J, NEUHAUS, Jacqueline, ABRAMS, Donald I, BOWER, Mark, GEY, Daniela, HATZAKIS, Angelos, HENRY, Keith, HIDALGO, Jose, LOURTAU, Leonardo, NEATON, James D, TAMBUSSI, Giuseppe
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 12.09.2007
• Subjects: Acquired Immunodeficiency Syndrome - complications; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - epidemiology; Adult; AIDS/HIV; Anti-Retroviral Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Cohort Studies; Female; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - epidemiology; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Incidence; Infectious diseases; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Lymphoma - epidemiology; Lymphoma - etiology; Male; Medical sciences; Middle Aged; Neoplasms - etiology; Pharmacology. Drug treatments; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - etiology; Recurrence; Risk Factors; RNA, Viral - analysis; Sarcoma, Kaposi - epidemiology; Sarcoma, Kaposi - etiology; Skin Neoplasms - epidemiology; Skin Neoplasms - etiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Antiretroviral agent; Lung; antiretroviral therapy; Microbiological investigation; Immunological investigation; CD4 T-cell counts; T-Lymphocyte; Antiviral; Clinical trial; Viral load; Human; Immunopathology; AIDS; Malignant tumor; Immune deficiency; Infection; Numeration; Chemotherapy; Treatment; HIV; Viral disease; Risk factor; randomized clinical trials; Skin; Arm; Prostate; Cancer
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e3282ed6338

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. A randomized clinical trial. 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. 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. 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.