Study Finds Potential Cancer Risk Biomarker in People Living With HIV

People living with HIV (PLWH) with a low CD4/CD8 ratio are at a higher risk of developing any form of cancer, according to a study published in Journal of the National Cancer Institute.

It is already known that PLWH are at higher risk of developing cancer than the general population, due to a combination of factors including immunosuppression and higher prevalence of smoking and cancer-causing viruses.

It is also known that low CD4/CD8 ratio is associated with harmful immune senescence, activation, and inflammation, all of which can potentially contribute to carcinogenesis and excess cancer risk in this population.

To evaluate whether low CD4/CD8 ratio is predictive of cancer among PLWH, researchers with the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) analyzed data from between 1998 and 2016.

This analysis included a total of 83,893 PLWH from 15 cohorts, and all included patients received at least 12 months of follow-up. The study also excluded PLWH who either already had cancer at the time of joining their cohort or developed cancer within 6 months of joining.

The study population was mostly male (86%) and White (43%), with 37% of patients being Black and 11% being Latinx. The median age at cohort entry was 43 years.

The median CD4 cell count was 437—normal CD4 count is between 500 to 1400 cells per cubic millimeter (mm³)—and the median CD4/CD8 ratio was 0.47 at NA-ACCORD entry. Most PLWH in this study were receiving antiretroviral therapy at entry or began soon after, and most (58%) had an undetectable viral load at the beginning of the follow-up period.

The authors also noted that 21% had hepatitis C, 7% had hepatitis B, 29% had a history of heavy alcohol use, and 33% had a history of smoking.

Among 83,893 PLWH, 5628 developed cancer, with 6.7% of PLWH in the cohort developing cancer during a median follow-up of 8.5 years. The most frequently diagnosed cancer was prostate cancer (n=801), followed by lung cancer (n=755), Kaposi sarcoma (n=501), non-Hodgkin lymphoma (n=497), anal cancer (n=439), liver cancer (n=347), and colorectal cancer (n=221).

The overall median 6-month lagged CD4/CD8 ratio was 0.52, with an IQR of 0.30-0.82.

On the lower end, a ratio of 0.30 was associated with an increased risk of any incident cancer by 24% (adjusted hazard ratio = 1.24; 95% CI, 1.14-1.35), compared with a 6-month lagged CD4/CD8 ratio of 0.80.

CD4/CD8 ratio was also inversely associated with all of the detected cancers in this study except for prostate cancer in adjusted analyses.

The authors found similar results using 12-, 18-, and 24-month lagged CD4/CD8 ratios. The 24-months lagged CD4/CD8 ratio resulted in a similar increased risk of 24% when compared with the 6-month lagged ratio.

According to the authors, the large population size and large amount of cancers detected in NA-ACCORD are major strengths of the study.

While crediting the CD4/CD8 ratio as a potential useful biomarker for certain cancers in PLWH, they also said further research is necessary to define how and when CD4/CD8 ratio can be used in cancer screening among PLWH.

Reference

Castilho JL, Bian A, Jenkins CA, et al. CD4/CD8 Ratio and Cancer Risk among Adults with HIV. J Natl Cancer Inst. Published online March 16, 2022. doi:10.1093/jnci/djac053