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In Reply:

Department of Clinical Immunology and Laboratory of Virology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France

Simonelli et al have reported a significant inverse correlation between the CD4+ cell count and the plasma human herpesvirus 8 (HHV-8) DNA load in five HIV-infected patients with primary effusion lymphoma (PEL), although no correlation could be found with their response to therapy.¹ In their response to our article,² the same authors reported in a heterogeneous population of 25 HIV-infected patients affected with multicentric Castleman disease (MCD), PEL, or HHV-8–associated solid extracavitary lymphomas, that patients with a plasma HHV-8 load higher than 40,000 copies/mL at the time of diagnosis, had a shorter survival time. However, this parameter could not be identified as an independent prognostic factor in a multivariate analysis.

During HHV-8 infection, HHV-8 DNA can be detected in both peripheral blood mononuclear cells (PBMCs; "cellular" viremia) and as cell-free HHV-8 DNA ("plasma" viremia). In HIV-associated MCD, a strong correlation has been found between the HHV-8 DNA load in PBMCs and the clinical symptoms of the disease.³ The majority of HHV-8 DNA present in the plasma is resistant to DNase digestion, suggesting that it is mostly virion associated.⁴ Plasma HHV-8 DNA levels had been associated with the clinical stage of Kaposi’s sarcoma (KS) and with response to highly active antiretroviral therapy (HAART).^5,6 As such, HHV-8 viremia is considered a useful marker for monitoring HIV-infected patients with MCD or KS. However, only few data are available for PEL.

In our article published in the July 1, 2005, issue of the Journal of Clinical Oncology,² of 28 HIV-infected patients with PEL, plasma samples collected at the time of PEL diagnosis were available in 21 cases (75%). The HHV-8 DNA load was determined on DNA preparations from 200 µL of plasma, using quantitative real-time PCR (Taqman) assay targeted to ORF26 (using the ABI PRISM 7500 Sequence Detection System; Perkin-Elmer, Wellesley, MA), as described by Oksenhendler et al.³ As shown in Table 1, the plasma HHV-8 DNA load ranged from undetectable to 754,373 copies/mL. HHV-8 plasma viremia was undetectable in four patients, all of whom were being treated with HAART. Among the 17 patients with detectable plasma HHV-8 DNA levels, the median value was 2,576 copies/mL. In univariate analysis, no statistically significant association was found between a plasma HHV-8 DNA load of more than 40,000 copies/mL and a shorter survival (P = .73; hazard ratio (HR) 1.23; 95% CI, 0.38 to 3.96). Similarly, using a cutoff value of 2,500 copies/mL, close to the median value, we failed to demonstrate any prognostic influence of plasma HHV-8 viral load on survival (P = .87; HR 1.1; 95%CI, 0.38 to 3.24).

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Simonelli C, Tedeschi R, Gloghini A, et al: Characterization of immunologic and virological parameters in HIV-infected patients with primary effusion lymphoma during antiblastic therapy and highly active antiretroviral therapy. Clin Infect Dis 40:1022-1027, 2005[CrossRef][Medline]

2. Boulanger E, Gerard L, Gabarre J, et al: Prognostic factors and outcome of human herpesvirus 8–associated primary effusion lymphoma in patients with AIDS. J Clin Oncol 23:4372-4380, 2005[Abstract/Free Full Text]

3. Oksenhendler E, Carcelain G, Aoki Y, et al: High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients. Blood 96:2069-2073, 2000[Abstract/Free Full Text]

4. Campbell TB, Borok M, Gwanzura L, et al: Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi’s sarcoma clinical stage. Aids 14:2109-2116, 2000[CrossRef][Medline]

5. Campbell TB, Borok M, White IE, et al: Relationship of Kaposi sarcoma (KS)-associated herpesvirus viremia and KS disease in Zimbabwe. Clin Infect Dis 36:1144-1151, 2003[CrossRef][Medline]

6. Bourboulia D, Aldam D, Lagos D, et al: Short- and long-term effects of highly active antiretroviral therapy on Kaposi sarcoma-associated herpesvirus immune responses and viraemia. AIDS 18:485-493, 2004[CrossRef][Medline]

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Related Correspondence

• Prognostic Factors in Human Herpesvirus 8–Related Lymphoproliferative Disorders Associated With HIV Infection
  Cecilia Simonelli, Rosamaria Tedeschi, Annunziata Gloghini, Michele Spina, Renato Talamini, Paolo De Paoli, Umberto Tirelli, and Antonino Carbone
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