Dysfunctional natural killer cells, in vivo, are governed by HIV viremia regardless of whether the infected individual is on antiretroviral therapy

Progression to AIDS during HlV-infection is associated with a decrease in the number and function of natural killer (NK) cells. The reduction in NK cells expressing CD56 and CD16 correlates with low CD4+ T-cell count and increasing viral load. Moreover, higher viral loads are associated with an increased presence of a highly dysfunctional NK cell subpopulation lacking CD56 but retaining CD16, whereas suppression of viral replication with highly-active antiretroviral therapy (HAART) results in improvements in both NK cell function and NK cell phenotype. These observations have been used to propose that high level viral replication is a consequence rather than a cause of alterations in the NK cell phenotypic patterns, although this remains controversial. Of note, most of these studies involved individuals who were either not controlling HIV replication or whose virus was fully controlled with HAART. No study has systematically included individuals whose virus was low in the absence of therapy, and presumably being controlled immunologically.