Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

INSIGHT START Study Group

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1668-1676
Number of pages9
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume63
Issue number12
DOIs
StatePublished - Dec 15 2016

Fingerprint

Virus Diseases
HIV
Infection
Neoplasms
Therapeutics
RNA
Risk Reduction Behavior
CD4 Lymphocyte Count
Cell Count
Confidence Intervals
Proportional Hazards Models
Sample Size

Keywords

  • antiretroviral therapy
  • cancer
  • HIV
  • Kaposi sarcoma
  • non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{1bf342fb77664989885771de9c49f0a5,
title = "Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection",
abstract = "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.",
keywords = "antiretroviral therapy, cancer, HIV, Kaposi sarcoma, non-Hodgkin lymphoma",
author = "{INSIGHT START Study Group} and Borges, {{\'A}lvaro H.} and Jacqueline Neuhaus and Babiker, {Abdel G.} and Keith Henry and Jain, {Mamta K.} and Adrian Palfreeman and Peter Mugyenyi and Pere Domingo and Christian Hoffmann and Read, {Tim R.H.} and Sanjay Pujari and Michael Meulbroek and Margaret Johnson and Timothy Wilkin and Ronald Mitsuyasu",
year = "2016",
month = "12",
day = "15",
doi = "10.1093/cid/ciw621",
language = "English (US)",
volume = "63",
pages = "1668--1676",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

AU - INSIGHT START Study Group

AU - Borges, Álvaro H.

AU - Neuhaus, Jacqueline

AU - Babiker, Abdel G.

AU - Henry, Keith

AU - Jain, Mamta K.

AU - Palfreeman, Adrian

AU - Mugyenyi, Peter

AU - Domingo, Pere

AU - Hoffmann, Christian

AU - Read, Tim R.H.

AU - Pujari, Sanjay

AU - Meulbroek, Michael

AU - Johnson, Margaret

AU - Wilkin, Timothy

AU - Mitsuyasu, Ronald

PY - 2016/12/15

Y1 - 2016/12/15

N2 - 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.

AB - 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.

KW - antiretroviral therapy

KW - cancer

KW - HIV

KW - Kaposi sarcoma

KW - non-Hodgkin lymphoma

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U2 - 10.1093/cid/ciw621

DO - 10.1093/cid/ciw621

M3 - Article

C2 - 27609756

AN - SCOPUS:85033367649

VL - 63

SP - 1668

EP - 1676

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 12

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