Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma.

OBJECTIVES: People living with HIV (PLWH) have elevated risk of non-Hodgkin lymphoma (NHL) and other diseases. Studying clonal hematopoiesis (CH), the clonal expansion of mutated hematopoietic stem cells, could provide insights regarding elevated NHL risk.

DESIGN: Cohort analysis of participants in the Multicenter AIDS Cohort Study (N = 5,979).

METHODS: Mosaic chromosomal alterations (mCAs), a type of CH, were detected from genotyping array data using MoChA. We compared CH prevalence in men living with HIV (MLWH) to HIV-uninfected men using logistic regression, and among MLWH, assessed the associations of CH with NHL incidence and overall mortality using Poisson regression.

RESULTS: Comparing MLWH to HIV-uninfected men, we observed no difference in the frequency of autosomal mCAs (3.9% vs. 3.6%, p-value=0.09) or mosaic loss of the Y chromosome (mLOY) (1.4% vs. 2.9%, p-value=0.13). Autosomal mCAs involving copy-neutral loss of heterozygosity (CN-LOH) of chromosome 14q were more common in MLWH. Among MLWH, mCAs were not associated with subsequent NHL incidence (autosomal mCA p-value=0.65, mLOY p-value=0.48). However, two MLWH with diffuse large B-cell lymphoma had overlapping CN-LOH mCAs on chromosome 19 spanning U2AF2 (involved in RNA splicing), and one MLWH with Burkitt lymphoma had high-frequency mCAs involving chromosome 1 gain and chromosome 17 CN-LOH (cell fractions 22.1% and 25.0%, respectively). mCAs were not associated with mortality among MLWH (autosomal mCA p-value=0.52, mLOY p-value=0.93).

CONCLUSIONS: We found limited evidence for a relationship between HIV infection and mCAs. Although mCAs were not significantly associated with NHL, mCAs detected in several NHL cases indicate a need for further investigation.