Associations Between Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid Levels and Incidence of Invasive Cancer in People With HIV After Initiation of Combination Antiretroviral Therapy

Olof Elvstam; Gaetano Marrone; Patrik Medstrand; Carl Johan Treutiger; Veronica Svedhem; Magnus Gisslén; Per Björkman

doi:10.1093/ofid/ofab131

Associations Between Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid Levels and Incidence of Invasive Cancer in People With HIV After Initiation of Combination Antiretroviral Therapy

Open Forum Infect Dis. 2021 Mar 17;8(6):ofab131. doi: 10.1093/ofid/ofab131. eCollection 2021 Jun.

Authors

Olof Elvstam¹, Gaetano Marrone², Patrik Medstrand¹, Carl Johan Treutiger³, Veronica Svedhem⁴, Magnus Gisslén^{5

6}, Per Björkman^{1

7}

Affiliations

¹ Department of Translational Medicine, Lund University, Malmö, Sweden.
² Department of Infectious Diseases and Clinical Virology, Karolinska University Hospital, Stockholm, Sweden.
³ Department of Infectious Diseases/Venhälsan, South General Hospital, Stockholm, Sweden.
⁴ Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
⁵ Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Department of Infectious Diseases, Skåne University Hospital, Malmö, Sweden.

Abstract

Background: Human immunodeficiency virus (HIV) viremia could be involved in the increased risk of cancer in people with HIV (PWH) receiving combination antiretroviral therapy (cART). We analyzed the association between plasma HIV ribonucleic acid levels in PWH starting cART and incident invasive cancer using the Swedish cohort InfCare HIV linked with national registers.

Methods: Adults starting cART in 1996-2017 were included if they had ≥1 viral load (VL) measurement before receiving any antiretroviral agent (pre-ART VL) and ≥2 VLs ≥6 months after start of cART. Viremia during cART was analyzed both as viremia-copy-years and categorized as suppression (<50 copies/mL), low-level viremia ([LLV] 50-999 copies/mL), and nonsuppression (≥1000 copies/mL). The main outcome was a composite of invasive malignancies with increased incidence among PWH. We fitted proportional subhazard models (including sex, age, pre-ART CD4 count, and injection drug use) for both pre-ART VL and viremia during cART.

Results: After 32 105 person-years, 3254 of 4931 participants (66%) were classified as suppressed, 438 (9%) were classified as LLV, and 1221 (25%) were classified as nonsuppressed. Neither viremia category nor cumulative viremia during cART had a statistically significant association with cancer. Higher pre-ART VL was associated with cancer (adjusted subhazard ratio, 1.4; 95% confidence interval, 1.0-1.8); this remained statistically significant with viremia during cART in the model. In subanalysis, the association with pre-ART VL was statistically significant for acquired immune deficiency syndrome (AIDS)-defining and infection-related non-AIDS-defining cancer, but not for other malignancies.

Conclusions: In this nationwide cohort, pre-ART VL was an independent predictor of invasive cancer, whereas viremia profile during cART was not associated with cancer incidence.

Keywords: HIV infection; acquired immunodeficiency syndrome; anti-retroviral agents; neoplasms; viremia.