Human herpesvirus-7 (HHV-7) is a CD4 T-lymphotropic betaherpesvirus, highly prevalent in the adult population. The pathogenic role of this virus still remains unclear. From data obtained in vitro, HHV-7 might be expected to slow the progression of HIV infection. Indeed, both viruses use the glycoprotein CD4 as a cell receptor, and a reciprocal competition has been demonstrated for entry in CD4 cells . Conversely, as for other herpesviruses, HHV-7 replication might be facilitated through the deficiency of immune control associated with HIV infection. In order to approach the question of interactions between both viruses in vivo, HHV-7 DNA was detected and quantified in the peripheral blood mononuclear cells (PBMC) from a control group of 31 HIV-seronegative individuals and two distinct groups of HIV-seropositive patients who had never received any antiretroviral therapy: 68 patients from the French ALT Cohort of long-term non-progressors (LTNP) , and 30 patients classified as progressors. HHV-7 DNAemia was studied using a real-time polymerase chain reaction assay based on TaqMan technology (we used the ABI PRISM 7700 sequence detection system; Applied Biosystems, Courtaboeuf, France) .
The rate of HHV-7 DNA detection was statistically lower in HIV-seropositive (38%) than in HIV-seronegative individuals (87%) (P < 0.0001). However, this HHV-7 detection rate in HIV-seropositive patients was much higher than the 3% value obtained by means of quantitative-competitive polymerase chain reaction applied to whole blood in a previous study , which probably reflects differences in both assay sensitivity and DNA input. This rate was also higher in LTNP (48%) than in progressors (20%) (P = 0.018). This difference fit the variation of median CD4 T-lymphocyte count, which was significantly higher in LTNP (678 cells/μl) than in progressors (314 cells/μl) (P < 0.0001). Moreover, considering both groups os of HIV-seropositive patients together, the median CD4 T-lymphocyte count was higher in patients with detectable HHV-7 DNA than in patients without (640 and 488 cells/μl, respectively) (P = 0.008). No correlation was observed between the rate of HHV-7-DNA detection and the HIV load.
In agreement with the results of viral detection, the median HHV-7 load was lower in HIV-seropositive patients [111 equivalent genome copy numbers (EqCop)/106 PBMC; 11–1333] than in HIV-seronegative individuals (987 EqCop/106 PBMC; 16–14 545) (P = 0.0004). Among HIV-seropositive patients, no statistical correlation was demonstrated between the HHV-7 load and either the HIV load or CD4 T-lymphocyte count, when considering all subjects as a whole or LTNP and progressors separately. Taking advantage of the fact that LTNP had been followed-up for a median time of 3 years, the analysis of HHV-7 DNAemia was repeated at one and 2 years after the initial evaluation; both detection rates (53 and 47%, respectively) and DNA loads (106 and 142 EqCop/106 PBMC, respectively) were found to be stable over that period.
The finding that HHV-7 DNAemia was detected more frequently in HIV-seronegative than in HIV-seropositive individuals, and in LTNP more frequently than in progressors, might support the idea that HHV-7 did compete with HIV in vivo. Alternatively, this might reflect the decrease in CD4 T-lymphocytes, a key cell reservoir for HHV-7, throughout the course of HIV infection. Intriguingly, either hypothesis hardly fits with the current absence of statistical correlation between the HHV-7 load, and either the HIV load or CD4 T-lymphocyte count. Further studies, involving both a larger number of subjects and patients receiving HIV replication inhibitors, are warranted to determine to what extent HHV-7 can be considered as a negative marker or a competitor for HIV progression.
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