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. 2021 Aug 2;73(3):e735-e744.
doi: 10.1093/cid/ciab087.

Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study

Yann Ruffieux  1 , Mazvita Muchengeti  2   3 , Matthias Egger  1   4   5 , Orestis Efthimiou  1   6 , Lina Bartels  1 , Victor Olago  2 , Maša Davidović  1   7 , Tafadzwa Dhokotera  1   2   8 , Julia Bohlius  1 , Elvira Singh  2   3 , Eliane Rohner  1
Affiliations

Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study

Yann Ruffieux et al. Clin Infect Dis. .

Abstract

Background: We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) in South Africa.

Methods: We used data from the South African HIV Cancer Match Study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported adjusted hazard ratios (aHRs) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µL decrease.

Results: Of 3 532 266 PLWH, 15 078 developed cancer. The most common cancers were cervical cancer (4150 cases), Kaposi sarcoma (2262 cases), and non-Hodgkin lymphoma (1060 cases). The association between lower CD4 cell count and higher cancer incidence rates was strongest for conjunctival cancer (aHR per 100 CD4 cells/µL decrease: 1.46; 95% confidence interval [CI], 1.38-1.54), Kaposi sarcoma (aHR, 1.23; 95% CI, 1.20-1.26), and non-Hodgkin lymphoma (aHR, 1.18; 95% CI, 1.14-1.22). Among infection-unrelated cancers, lower CD4 cell counts were associated with higher incidence rates of esophageal cancer (aHR, 1.06; 95% CI, 1.00-1.11) but not breast, lung, or prostate cancer.

Conclusions: Lower CD4 cell counts were associated with an increased risk of developing various infection-related cancers among PLWH. Reducing HIV-induced immunodeficiency may be a potent cancer-prevention strategy among PLWH in sub-Saharan Africa, a region heavily burdened by cancers attributable to infections.

Keywords: CD4 cell count; HIV; South Africa; cancer; immunodeficiency.

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Figures

Figure 1.
Figure 1.
Adjusted hazard ratios (solid lines) with 95% confidence intervals (gray area) for the incidence of AIDS-defining cancers, comparing a grid of CD4 cell counts with the reference value of 200 cells/µL. The models are adjusted for sex, age, calendar year, and diagnosis of other cancers.
Figure 2.
Figure 2.
Adjusted hazard ratios (solid lines) with 95% confidence intervals (gray area) for the incidence of infection-related, non–AIDS-defining cancers, comparing a grid of CD4 cell counts with the reference value of 200 cells/µL. The models are adjusted for sex, age, calendar year, and diagnosis of other cancers. Abbreviations: EBV, Epstein-Barr virus; HPV, human papillomavirus.
Figure 3.
Figure 3.
Adjusted hazard ratios (solid lines) with 95% confidence intervals (gray area) for the incidence of infection-unrelated cancers, comparing a grid of CD4 cell counts with the reference value of 200 cells/µL. The models are adjusted for sex, age, calendar year, and diagnosis of other cancers.
Figure 4.
Figure 4.
Adjusted hazard ratios for cancer incidence with associated 95% confidence intervals, per 100 cells/µL decrease in CD4 cell count. The models assumed a linear relationship between CD4 cell count and the log-hazard of the cancer, while adjusting for sex, age, calendar year, and diagnosis of other cancers. The cancers are ranked in decreasing order of their adjusted hazard ratios. Abbreviations: EBV, Epstein-Barr virus; HPV, human papillomavirus.
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