Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study

Data Collection of Adverse Events of Anti-HIV drugs (D:A:D) Study group

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)


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 × 10 9 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 × 10 9 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 × 10 9 cells/L and less than 350 × 10 9 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.

Original languageEnglish
Pages (from-to)768-776
Number of pages9
JournalAnnals of Internal Medicine
Issue number6
Publication statusPublished - 1 Jun 2021

Bibliographical note

Funding Information:
Financial Support: The D:A:D study was supported by grant DNRF126 from the Danish National Research Foundation (Centre of Excellence for Health, Immunity and Infections [CHIP] and Personalized Medicine of Infectious Complications in immune deficiency [PERSIMUNE]); the Highly Active Anti-retroviral Therapy Oversight Committee, a collaborative committee with representation from academic institutions; the European Agency for the Evaluation of Medicinal Products; the U.S. Food and Drug Administration; the patient community; and the following pharmaceutical companies with licensed anti-HIV drugs in the European Union: AbbVie, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck & Co., and Janssen Pharmaceuticals. It was also supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Center for Infectious Disease Control of the National Institute for Public Health and the Environment to Stichting HIV Monitoring (ATHENA [AIDS Therapy Evaluation Project Netherlands]); by a grant from the Agence nationale de recherches sur le sida et les hépatites virales (Action Coordonnée no. 7, Cohortes) to the Aquitaine Cohort; by grant FIS 99/0887 from the Fondo de Investigación Sanitaria and grant FIPSE 3171/00 from the Fundación para la Investigación y la Prevención del SIDA en España to the Barcelona Antiretroviral Surveillance Study; by grants 5U01AI042170-10 and 5U01AI046362-03 from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to the Terry Beirn Community Programs for Clinical Research on AIDS; by primary funding provided by the European Union's Seventh Framework Programme for research, technological development, and demonstration under EUROCOORD grant agreement 260694; by unrestricted grants from Bristol-Myers Squibb, Janssen R&D, Merck & Co., Pfizer, and GlaxoSmithKline (the participation of centers from Switzerland is supported by grant 108787 from the Swiss National Science Foundation) to the EuroSIDA study; by unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Pfizer, and Janssen Pharmaceuticals to the ICONA (Italian Cohort Naive Antiretro-virals) Foundation; and by financing within the framework of the Swiss HIV Cohort Study, supported by grant 148522 from the Swiss National Science Foundation and by the Swiss HIV Cohort Study research foundation. The Australian HIV Observational Database is funded as part of the Asia Pacific HIV Observational Database, a program of the Foundation for AIDS Research (amfAR), and is supported in part by grant U01-AI069907 from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and by unconditional grants from Merck & Co., Gilead Sciences, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen-Cilag, and ViiV Healthcare. The Kirby Institute is funded by the Australian government Department of Health and Ageing and is affiliated with the Faculty of Medicine at the University of New South Wales. This study was additionally funded by grant KFS-4106-02-2017 from Swiss Cancer League/Swiss Cancer Research and by Stiftung Institut fu€r klinische Epidemiologie. Dr. Lodi was supported by grant P30AI042853 from the Providence/Boston Center for AIDS Research.

Publisher Copyright:
© 2021 American College of Physicians.


Dive into the research topics of 'Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study'. Together they form a unique fingerprint.

Cite this