Human herpesvirus 6 in human immunodeficiency virus‐infected individuals: Association with early histologic phases of lymphadenopathy syndrome but not with malignant lymphoproliferative disorders

Preliminary evidence suggested that human herpesvirus‐6 (HHV‐6) may act as a cofactor in acquired immunodeficiency syndrome (AIDS) and may contribute to the pathogenesis of lymphoproliferative disorders occurring in individuals infected with the human immunodeficiency virus (HIV). To understand better the biological and clinical significance of HHV‐6 infection in the context of HIV‐related immunosuppression, the polymerase chain reaction was used to study the frequency and variant distribution of HHV‐6 in peripheral blood mononucleated cells (PBMCs) from HIV‐seropositive individuals, either asymptomatic or with lymphadenopathy syndrome (LAS) or with overt AIDS. Non‐neoplastic and malignant lymphoproliferative disorders from both HIV‐infected and HIV‐seronegative patients were also investigated using the same series of samples for the presence of Epstein‐Barr virus (EBV). When compared with healthy blood donors (12/42, 29%), HHV‐6 prevalence in PBMCs showed a progressive decline in HIV‐seropositive individuals with asymptomatic HIV infection (3/26, 11%) and in patients with LAS (1/13, 8%) and a significant reduction in patients with overt AIDS (1/20, 20%; P = 0.02). The decrease correlated with the number of CD4+ cells at the time of examination. In addition, HHV‐6 DNA sequences were significantly more prevalent in LAS biopsies (13/20, 65%) than in HIV‐unrelated reactive lymphadenopathies (2/10, 20%; P = 0.02) and the presence of HHV‐6 sequences correlated closely with a histologic pattern of follicular hyperplasia (13/16, 81%; P = 0.003). Strikingly, HHV‐6 prevalence decreased in PBMCs of LAS patients, suggesting that the likelihood of interactions between HHV‐6 and HIV varies in different body districts. In particular, the demonstration that all HHV‐6‐carrying LAS samples were also positive for HIV infection suggests that LAS lymph nodes constitute one of the sites where biologically relevant interactions between the two viruses might occur. Also, the prevalence of EBV was higher in LAS (14/20, 70%) than in non‐neoplastic lymph nodes from HIV‐seronegative individuals (4/10, 40%), although the difference was not statistically significant. EBV was associated strongly with HIV‐related malignant lymphoproliferative disorders, being detected in 100% of patients with Hodgkin's disease (HD) and 53% of B‐cell non‐Hodgkin's lymphomas (NHL). In contrast, the prevalence of HHV‐6 DNA in HD and B‐cell NHL arisen in HIV‐infected patients (30% and 6%, respectively) was remarkably lower and similar to that observed in lymphoproliferative disorders from HIV‐seronegative patients. Finally, as observed in healthy individuals, HHV‐6 variant B was more prevalent than variant A in benign and malignant lymphoproliferative disorders from both HIV‐infected and HIV‐seronegative patients. These results suggest that the interactions between HHV‐6 and HIV could be different in the various phases of HIV disease and in different districts; HHV‐6 has probably no direct role in the pathogenesis of HIV‐associated B‐cell NHL and HD cases, and behave differently from EBV; and HIV‐related immunosuppression does not alter the distribution of HHV‐6 variants in these tissues, as observed in the case of EBV. © 1996 Wiley‐Liss, Inc.