Frontiers in microbiology · 2026
HHV-8 genotypes and clinical features in Kaposi sarcoma and primary effusion lymphoma in people living with HIV in Salvador, Brazil.
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Benevides Carlos Frederico Lopes, Stocker Andreas, Vieira Sueli Moreno, Luz Estela, Brites Carlos
Аннотация
INTRODUCTION: Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi sarcoma (KS) and primary effusion lymphoma (PEL), important causes of morbidity and mortality among people living with HIV (PLWH). The highly polymorphic ORF-K1 region is commonly used for HHV-8 genotyping and phylogenetic analysis. We investigated the distribution of HHV-8 genotypes and their clinical correlates among PLWH diagnosed with KS or PEL in Salvador, Brazil.
METHODS: Between 2022 and 2025, biological specimens from PLWH with KS or PEL were prospectively collected, including skin biopsies, blood, pleural effusions, and serum samples. HHV-8 DNA was detected by real-time PCR, and positive samples underwent semi-nested PCR amplification and sequencing of the ORF-K1 region. Phylogenetic analyses were performed using Maximum Likelihood reconstruction with 602 reference HHV-8 K1 sequences obtained from GenBank. Clinical, virological, and immunological data were analyzed according to HHV-8 genotype.
RESULTS: HHV-8 DNA was successfully sequenced in 14 of 19 samples. Phylogenetic analysis identified subtype C in 7/14 (50.0%) cases, subtype B in 4/14 (28.6%), and subtype A in 3/14 (21.4%). Most participants were men who have sex with men (86.6%), with a median age of 34 years. Among 13 patients with available clinical data, eight (61.5%) presented with high-risk KS or PEL. Genotype A was detected in patients with aggressive disease manifestations, including visceral KS and PEL, whereas subtype C was predominantly associated with mucocutaneous disease. However, no statistically significant association was observed between genotype and disease severity (Fisher-Freeman-Halton exact test, p = 0.4639). Phylogenetic reconstruction also identified a distinct cluster containing two previously reported A5 isolates that segregated from recognized HHV-8 subtypes.
DISCUSSION: HHV-8 subtype C was the predominant genotype among PLWH with KS or PEL in Salvador, followed by subtypes B and A. Although limited by sample size, subtype A was observed only in patients with severe diseases, consistent with previous reports suggesting an association between subtype A and severe clinical presentations. The identification of a distinct phylogenetic branch expands current knowledge of HHV-8 genetic diversity and warrants further investigation. These findings improve understanding of HHV-8 molecular epidemiology and provide insights for future studies evaluating genotype-phenotype associations.
METHODS: Between 2022 and 2025, biological specimens from PLWH with KS or PEL were prospectively collected, including skin biopsies, blood, pleural effusions, and serum samples. HHV-8 DNA was detected by real-time PCR, and positive samples underwent semi-nested PCR amplification and sequencing of the ORF-K1 region. Phylogenetic analyses were performed using Maximum Likelihood reconstruction with 602 reference HHV-8 K1 sequences obtained from GenBank. Clinical, virological, and immunological data were analyzed according to HHV-8 genotype.
RESULTS: HHV-8 DNA was successfully sequenced in 14 of 19 samples. Phylogenetic analysis identified subtype C in 7/14 (50.0%) cases, subtype B in 4/14 (28.6%), and subtype A in 3/14 (21.4%). Most participants were men who have sex with men (86.6%), with a median age of 34 years. Among 13 patients with available clinical data, eight (61.5%) presented with high-risk KS or PEL. Genotype A was detected in patients with aggressive disease manifestations, including visceral KS and PEL, whereas subtype C was predominantly associated with mucocutaneous disease. However, no statistically significant association was observed between genotype and disease severity (Fisher-Freeman-Halton exact test, p = 0.4639). Phylogenetic reconstruction also identified a distinct cluster containing two previously reported A5 isolates that segregated from recognized HHV-8 subtypes.
DISCUSSION: HHV-8 subtype C was the predominant genotype among PLWH with KS or PEL in Salvador, followed by subtypes B and A. Although limited by sample size, subtype A was observed only in patients with severe diseases, consistent with previous reports suggesting an association between subtype A and severe clinical presentations. The identification of a distinct phylogenetic branch expands current knowledge of HHV-8 genetic diversity and warrants further investigation. These findings improve understanding of HHV-8 molecular epidemiology and provide insights for future studies evaluating genotype-phenotype associations.