Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up

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Abstract

Purpose

Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors.

Methods

We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004–2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors.

Results

Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use.

Conclusion

Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00432-023-05500-9.

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Most cited references 40

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Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration

Colette J Smith, Lene Ryom, Rainer Weber … (2014)

With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011.

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Spectrum of cancer risk among HIV-infected people in the United States during the modern antiretroviral therapy era: a population-based registry linkage study

Raúl Hernández-Ramírez, Meredith Shiels, Robert Dubrow … (2017)

Background Monitoring cancer risk among HIV-infected people in the modern antiretroviral therapy (ART) era is critical given their elevated risk for many cancers and prolonged survival with immunosuppression, ART exposure, and aging. Our study described cancer risk in HIV-infected people in the United States relative to the general population. Methods Utilizing data from linked population-based HIV and cancer registries (nine areas; 1996–2012), we calculated standardized incidence ratios (SIRs). We tested SIR differences by AIDS status and over time using Poisson regression. Findings Among 448,258 HIV-infected people, risk was elevated (p<0·0001) for cancer overall (SIR 1·69; 95%CI: 1·67–1·72), AIDS-defining cancers (Kaposi sarcoma [498; 478–519], non-Hodgkin lymphoma [11·5; 11·1–11·9], and cervix [3·24; 2·94–3·56]), most other virus-related cancers (e.g., anus [19·1; 18·1–20·0], liver [3·21; 3·02–3·41], and Hodgkin lymphoma [7·70; 7·20–8·23]), and some virus-unrelated cancers (e.g., lung [1·97; 1·89–2·05]), but not for other common cancers. Risk for several cancers was higher after AIDS onset and declined across calendar periods. After multivariable adjustment, SIRs decreased significantly across 1996–2012 for six cancers (Kaposi sarcoma, two non-Hodgkin lymphoma subtypes, anus, liver, and lung) but remained elevated in the latest period. SIRs did not increase over time for any cancer. Interpretation Risks for several virus-related cancers and lung cancer declined among HIV-infected people, likely reflecting ART expansion since 1996. Despite declines, risk for many cancers remain elevated in the modern treatment era. Funding National Cancer Institute.

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Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment.

Allan R Tenorio, Yu Zheng, Ronald Bosch … (2014)

Defining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events. We conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders. Higher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes. Interventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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Author and article information

Contributors

Marta Rava:

ORCID: http://orcid.org/0000-0003-2260-9370

mrava@isciii.es

Journal

Journal ID (nlm-ta): J Cancer Res Clin Oncol

Journal ID (iso-abbrev): J Cancer Res Clin Oncol

Title: Journal of Cancer Research and Clinical Oncology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0171-5216

ISSN (Electronic): 1432-1335

Publication date (Electronic): 26 November 2023

Publication date PMC-release: 26 November 2023

Publication date (Print): 2023

Volume: 149

Issue: 20

Pages: 18161-18171

Affiliations

[1 ]Grupo de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario Infanta Sofía, FIIB HUIS HHEN, ( https://ror.org/05dfzd836) Madrid, Spain

[2 ]CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, ( https://ror.org/00ca2c886) Madrid, Spain

[3 ]Department of Medicine, Universidad Europea de Madrid, ( https://ror.org/04dp46240) Madrid, Spain

[4 ]GRID grid.411093.e, ISNI 0000 0004 0399 7977, Hospital General Universitario de Elche and Universidad Miguel Hernández, ; Alicante, Spain

[5 ]Hospital Universitario Ramón y Cajal, IRYCIS, ( https://ror.org/050eq1942) Madrid, Spain

[6 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Hospital Gregorio Marañón Servicio de Enfermedades Infecciosas/Microbiología Clínica Instituto de Investigación Gregorio Marañón, ; Madrid, Spain

[7 ]Hospital Universitario La Paz, ( https://ror.org/01s1q0w69) Madrid, Spain

[8 ]GRID grid.411083.f, ISNI 0000 0001 0675 8654, Infectious Diseases Department, , Vall d’Hebron Research Institute (VHIR), Hospital Universitari Vall d’Hebron, ; Barcelona, Spain

[9 ]Servicio de Medicina Interna, Hospital Clínico Universitario de Valladolid, ( https://ror.org/04fffmj41) Valladolid, Spain

[10 ]Infectious Diseases Unit, Hospital Universitario Central de Asturias and Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), ( https://ror.org/05xzb7x97) Oviedo, Spain

[11 ]GRID grid.507938.0, Hospital de La Marina Baixa, ; Alicante, Spain

[12 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Centro Nacional de Epidemiologia, , Instituto de Salud Carlos III, ; Madrid, Spain

Author information

Marta Rava http://orcid.org/0000-0003-2260-9370

Article

Publisher ID: 5500

DOI: 10.1007/s00432-023-05500-9

PMC ID: 10725373

PubMed ID: 38008809

SO-VID: 25c08cb9-df34-4b88-a8d4-54dc12a43e55

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 25 July 2023

Date accepted : 30 October 2023

Funding

Funded by: Gilead Scholarship Program for Biomedical Research

Award ID: GLD19_00106

Award Recipient : Marta Rava

Funded by: ISCIII- Miguel Servet

Award ID: CP19CIII - 00002 contract

Award Recipient : Marta Rava

Funded by: Instituto de Salud Carlos III

Open Access :

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer,mortality,hiv,cohort study

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer, mortality, hiv, cohort study

Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up

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Most cited references 40

Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration

Spectrum of cancer risk among HIV-infected people in the United States during the modern antiretroviral therapy era: a population-based registry linkage study

Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment.

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