Interactions between β-herpesviruses and human immunodeficiency virus in vivo: Evidence for increased human immunodeficiency viral load in the presence of human herpesvirus 6

In vitro, β-herpesviruses can stimulate or inhibit HIV replication under particular circumstances. In order to investigate the effects of β- herpesvirus infection on HIV replication and vice versa at an organ level, we determined the quantitative relationships between cytomegalovirus (CMV), human herpesviruses (HHV) 6 and 7, and HIV-1 proviral DNA using quantitative competitive PCR methods in 141 organs collected at autopsy from 11 AIDS patients. The presence of HHV-6 DNA in an organ was significantly associated with elevated HIV-1 proviral DNA (difference in HIV median loads, 1.3 log₁₀ genomes; P = 0.004). Consistent with this, there was a trend for the presence of HIV-1 proviral DNA to be associated with an elevated HHV-6 load (0.44 log₁₀ difference; P = 0.07). In contrast, there were no significant differences between vital loads in the combinations of either CMV or HHV-7 with HIV-1 proviral DNA load. Pairwise combinations of the β-herpesviruses revealed that the quantity of HHV-7 was increased in the presence of HHV-6 (difference in median loads, 1.3 log₁₀; P= 0.001) and the quantity of HHV- 6 was increased in the presence of HHV-7 (difference in median loads, 0.7 log₁₀; P= 0.002). These results demonstrate that the presence of HHV-6 in an organ is significantly associated with an elevated HIV-1 proviral load and have implications for understanding HIV pathogenesis in the human host and the role that β-herpesviruses, especially HHV-6, might play as cofactors in the HIV disease process.