The Sordid Affair Between Human Herpesvirus and HIV

Abstract

Both human immunodeficiency virus (HIV) and human herpesvirus (HHV) infections persist lifelong, and almost all individuals infected with HIV are also infected with ≥1 HHV. These coinfections are not independent processes or benign. In this review, we discuss how HHVs, and cytomegalovirus in particular, interact with concurrent HIV infection, and we describe the next steps necessary to understand and address these connections.

Keywords: HIV; Human herpesvirus; cytomegalovirus; epidemiology transmission; inflammation; pathogenesis.

Figure 1.

Theoretical model connecting asymptomatic cytomegalovirus (CMV) replication with human immunodeficiency virus (HIV) transmission (blue line), larger HIV DNA reservoir (green line), and end-organ disease (purple line). We hypothesize a circular feedback loop between CMV and HIV replication, immune activation and proliferation, and cell dysfunction (senescence and exhaustion) (red loop). In other words, CMV and HIV replication are probably responsible for increasing immune activation and T-cell dysfunction, which in turn further enhance CMV and HIV replication. This persistent immune activation has been repeatedly associated with neurocognitive and cardiovascular disease, aging, and increased viral reservoir, and CMV is probably part of that mechanism.