# Hodgkin Lymphoma in PLWH in South Africa: TB, EBV, and Tumor Molecular Markers

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $848,142

## Abstract

PROJECT SUMMARY
 Hodgkin lymphoma (HL) outcomes in PLWH in South Africa (S.A.) are inferior to those in HIV(-) patients,
although outcomes compare favorably in clinical trials. Advanced stage disease and consistent EBV-association
are well recognized in PLWH. In S.A., at the time of diagnosis, some PLWH are in such poor clinical condition
that they are not treated. Diagnostic delays contribute to late presentations, as HL diagnoses require surgical
biopsies for a definitive pathologic evaluation. Resources and infrastructure in S.A. are limited in this regard.
 To better understand disparate outcomes in PLWH in standard-of-care settings, we propose a prospective
observational study of HIV(+) and HIV(-) HL in S.A. (Aim 1). Performance status (PS), organ function, clinical
stage, tumor histological subtype, EBV association, and mutational landscape will all be assessed, as will
chemotherapy regimen, response to treatment, and cause of death, as determined by a minimally invasive
autopsy in consenting participants. Since tuberculosis (TB) is the leading cause of death in PLWH in S.A., the
symptoms of which mimic HL, HL patients are often empirically treated and repeatedly tested for TB before
excisional biopsies are pursued. A high co-infection rate coupled with immunosuppressive chemotherapy may
lead to TB progression in PLWH during therapy, and may contribute to ultimate mortality. Therefore, Aim 1 will
also have a major focus on the contributions of TB. The results of this study will lead to a better understanding
of the roles that PS, organ function and TB have in HL prognosis in PLWH, as well as aspects of the EBV
association and the mutational features.
 The near uniform association of EBV in HIV(+) HL may aid in the recognition of HL in PLWH via a non-invasive
plasma EBV test that can identify patients needing urgent excisional biopsy. To explore this possibility, we
propose to develop a diagnostic algorithm (Aim 2A) in a discovery cohort of PLWH with HL and without
malignancy. EBV DNA will be assessed along with additional plasma markers to increase specificity. The optimal
combination of markers will be used to develop an algorithm that will be tested in a validation cohort of high risk
PLWH (Aim 2B). Baseline PS and organ function will be obtained, and a rigorous yearlong follow-up will ensure
accurate classification of persons with lymphoma. In those who are diagnosed with HL or other lymphoma, PS
and organ function will be re-assessed. Participants who experience a marked decline in these measures, to the
point that they do not receive standard chemotherapy, will be considered potential “lives saved” if the diagnostic
algorithm could be applied clinically. We note that much of the infrastructure needed to implement the molecular
techniques is available in S.A., and that our South African collaborators have a track record of introducing
sophisticated molecular diagnostics for TB to the entire country.
1

## Key facts

- **NIH application ID:** 10825552
- **Project number:** 5R01CA250069-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RICHARD Frederick AMBINDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $848,142
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825552

## Citation

> US National Institutes of Health, RePORTER application 10825552, Hodgkin Lymphoma in PLWH in South Africa: TB, EBV, and Tumor Molecular Markers (5R01CA250069-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10825552. Licensed CC0.

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