Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.
BACKGROUND
In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.


METHODS
Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.


RESULTS
There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.


CONCLUSIONS
Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.
Centre for Health and Infectious Diseases Research, Department of Infectious Diseases, Section 2100, Rigshospitalet, University of Copenhagen, Denmark.
Álvaro H
ÁH
Borges
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
Jacqueline
J
Neuhaus
Medical Research Council Clinical Trials Unit, University College London, United Kingdom.
Abdel G
AG
Babiker
Hennepin County Medical Center, Minneapolis, Minnesota.
Keith
K
Henry
Division of Infectious Disease, UT Southwestern Medical Center, Dallas, Texas.
Mamta K
MK
Jain
Department of Infectious Diseases, University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
Adrian
A
Palfreeman
Joint Clinical Research Center, Kampala, Uganda.
Peter
P
Mugyenyi
Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA, Barcelona, Spain.
Pere
P
Domingo
Infektionsmedizinisches Centrum Hamburg Study Center, Hamburg.|Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany.
Christian
C
Hoffmann
Melbourne Sexual Health Centre, Alfred Hospital and Central Clinical School, Monash University, Australia.
Tim R H
TR
Read
Institute of Infectious Diseases, Pune, Maharashtra, India.
Sanjay
S
Pujari
Projecte dels Noms/Hispanosida, Barcelona, Spain.
Michael
M
Meulbroek
Ian Charleson Day Centre, Royal Free Hospital, London, United Kingdom.
Margaret
M
Johnson
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York.
Timothy
T
Wilkin
Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles.
Ronald
R
Mitsuyasu
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000517:prevention & control*; D040242:Risk Reduction Behavior; D061665:Time-to-Treatment
D019380:Anti-HIV Agents
HIV; Kaposi sarcoma; antiretroviral therapy; cancer; non-Hodgkin lymphoma