Cytomegalovirus viremia and advanced HIV disease: is there an argument for anti-CMV treatment?

The role of cytomegalovirus (CMV) infection as a co-factor in HIV disease has been a topic of considerable interest since the beginning of the HIV pandemic. CMV is believed to function both as a co-factor in the progression of HIV infection, and as a contributor to enhanced disease for other opportunistic infections.In this special article, we review several recent studies that have enhanced our understanding of the role that CMV infection plays in the natural history of other HIV-related opportunistic infections. We review the clinical evidence that demonstrates how CMV viremia has emerged as an independent risk factor for the progression of infections such as those caused by C. neoformans and M. tuberculosis. We outline the biological underpinnings of the various hypotheses by which CMV, as an immunomodulatory virus, may modify the natural history of HIV-related infections.Evidence suggests that active CMV replication, manifest as CMV viremia (DNAemia), may play a key role in driving progression of HIV-associated opportunistic infections. We propose that control of CMV replication, independent of the known benefit of HAART therapy on reducing CMV end-organ disease, could reduce the risk of disease and mortality attributable to opportunistic infections such as cryptococcosis and tuberculosis. This could be achieved by the targeted use of CMV antivirals. The advent of newer (and safer) orally bioavailable CMV antivirals has renewed interest in, and opportunities for, randomized controlled trials to evaluate CMV viremia as a modifiable risk factor in high-risk persons with HIV disease.