Despite treatment with combination antiretroviral therapy (cART), patients with HIV infection with low CD4/CD8 ratios had an increased risk of developing Kaposi sarcoma (KS), and those with high CD8 counts had an increased risk of developing non-Hodgkin lymphoma (NHL), according to results of a study published in Clinical Infectious Diseases.

Using data obtained from a large cohort collaboration conducted in 12 countries in Europe between 2000 and 2014, researchers aimed to evaluate the relationship between CD4/CD8 ratio restoration and the risk for KS or NHL in patients with HIV infection who achieved virologic control (plasma HIV-1 RNA ≤ 500 copies/mL) within 9 months of initiating treatment with cART. A secondary analysis included a total of 19,133 patients with CD4 counts of 500/mm3 or greater at baseline.

Using spline transformations, the researchers analyzed CD4/CD8 ratio, CD4 count, and CD8 count as time-dependent variables. Baseline was the time of the first CD4/CD8 measurement within 6 months after virologic control, with persistent suppressed viremia.


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Of the 56,708 patients (median age, 38 years) included in the analysis, 49% were men who have sex with men (MSM) and 25% were women. The median follow-up period was 59 months from baseline. At baseline, the median CD4 count, CD8 count, and CD4/CD8 ratio were 414/mm3 (interquartile range [IQR], 296-552), 936/mm3 (IQR, 670-1304), and 0.43 (IQR, 0.28-0.65), respectively. A total of 221 patients were diagnosed with KS 9 months (IQR, 2-37) after baseline, and 187 were diagnosed with NHL 18 months (IQR, 7-42) after baseline.

After adjustment for CD4 count and viral load, the researchers observed that a low CD4/CD8 ratio was associated with an increased risk for KS. Compared with a CD4/CD8 ratio of 1, a CD4/CD8 ratio of 0.8 yielded a hazard ratio (HR) of 1.18 (95% CI, 0.98-1.42), and a CD4/CD8 ratio of 0.3 yielded an HR of 2.02 (95% CI, 1.23-3.31). The inverse association between CD4/CD8 ratio and the risk for KS was significantly increased among patients with CD4 counts of 500/mm3 or greater at baseline.

Although a low CD4/CD8 ratio was not associated with an increased risk for NHL, the risk for NHL significantly increased among patients with high CD8 counts. Compared with a CD8 count of 1000/mm3, a CD8 count of 2000/mm3 yielded an HR of 1.61 (95% CI, 1.09-2.37), and a CD8 count of 3000/mm3 yielded an HR of 3.14 (95% CI, 1.58-6.22). Secondary analyses showed that the association between CD4/CD8 ratio and the risk for KS and CD8 count and the risk for NHL was significantly increased among patients with CD4 counts of 500/mm3 or greater at baseline.

Other independent factors associated with an increased risk for KS and NHL were virologic failure and older age. In addition, patients who were MSM had an increased risk for KS, whereas men had an increased risk for NHL.

Limitations of this study included “the absence of information on KS clinical presentation, NHL histological subtypes, and viral serostatus associated with NHL,” the researchers noted.

“Further studies are needed to clarify the impact of the CD4/CD8 ratio on the risk for other HIV-related diseases, to know which specific preventives measures could be implemented,” the researchers concluded.

Disclosure: Some study author(s) declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Caby, F, Guiguet M, Weiss L, et al; the (CD4/CD8 ratio and cancer risk) project working group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord. CD4/CD8 ratio and the risk of Kaposi sarcoma or non-Hodgkin lymphoma in the context of efficiently treated human immunodeficiency virus (HIV) infection: a collaborative analysis of 20 European cohort studies. Clin Infect Dis. 2021;73(1):50-59. doi:10.1093/cid/ciaa1137