TY - JOUR
T1 - Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy
T2 - A multinational prospective cohort study
AU - D:A:D Study Group
AU - Chammartin, Frederique
AU - Lodi, Sara
AU - Logan, Roger
AU - Ryom, Lene
AU - Mocroft, Amanda
AU - Kirk, Ole
AU - D'Arminio Monforte, Antonella
AU - Reiss, Peter
AU - Phillips, Andrew
AU - El-Sadr, Wafaa
AU - Hatleberg, Camilla I.
AU - Pradier, Christian
AU - Bonnet, Fabrice
AU - Law, Matthew
AU - De Wit, Stephane
AU - Sabin, Caroline
AU - Lundgren, Jens D.
AU - Bucher, Heiner C.
AU - Calvo, G.
AU - Dabis, F.
AU - Morfeldt, L.
AU - Weber, R.
AU - Lind-Thomsen, A.
AU - Salbøl Brandt, R.
AU - Hillebreght, M.
AU - Zaheri, S.
AU - Wit, F. W.N.M.
AU - Scherrer, A.
AU - Schoni-Affolter, F.
AU - Rickenbach, M.
AU - Tavelli, A.
AU - Fanti, I.
AU - Leleux, O.
AU - Mourali, J.
AU - Le Marec, F.
AU - Boerg, E.
AU - Thulin, E.
AU - Sundstrom, A.
AU - Bartsch, G.
AU - Thompsen, G.
AU - Necsoi, C.
AU - Delforge, M.
AU - Fontas, E.
AU - Caissotti, C.
AU - Dollet, K.
AU - Mateu, S.
AU - Torres, F.
AU - Petoumenos, K.
AU - Blance, A.
AU - Rozentale, B.
N1 - Publisher Copyright:
© 2021 American College of Physicians.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts < 350 and < 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.
AB - Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts < 350 and < 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.
UR - http://www.scopus.com/inward/record.url?scp=85108303283&partnerID=8YFLogxK
U2 - 10.7326/M20-5226
DO - 10.7326/M20-5226
M3 - Article
C2 - 33721519
AN - SCOPUS:85108303283
SN - 0003-4819
VL - 174
SP - 768
EP - 776
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 6
ER -