Activation markers predict subsequent increases in viremia in patients on suppressive HAART.

Ostrowski SR, Thiim P, Ullum H, Pedersen BK, Gerstoft J, Katzenstein TL. AIDS Laboratory, Rigshospitalet, Copenhagen (Denmark).

Background: Only a minority of the patients obtaining profound viral suppression in response to HAART maintains this degree of virological response. Markers predicting imminent viral rebound – either as true rebounds or in the form of low-grade viremia / blips are lacking. Material and Methods: Two years prospective follow-up among patients with HIV RNA < 200 copies/ml (n=103) in response to HAART. Data on this cohort has previously been reported 1.An extensive FACS profile describing the CD4, CD8 and NK populations was performed at baseline and half-yearly. Viral load was measured every three months. Results: The median HIV RNA at baseline was < 20 copies/ml with no significant increase in viremia during follow-up. 31 % had viremia persistently £ 20, while the other patients had ³ 1 measurement with some degree of detectable viremia. During follow-up the percentages of naïve non-activated CD4 cells increased (e.g. CD4+CD45RA+CD62L+, CD4+CD45RA+CD28+ and CD8-CD28+CD11A+), while activated memory cells decreased. In a mixed linear model a 10-fold increase in HIV replication was associated with concurrent increased amounts of CD8-CD38+HLA-DR+ cells (on a log-2 scale). In logistic regression analysis (corrected for CD4 at initiation of HAART, years from detection of HIV Ab to start of HAART and an AIDS diagnosis) a 2-fold increase in the amount of CD4+HLA-DR+ cells were associated with increased viremia three months later (OR 1.61 (1.28-2.02)), while a 2-fold increase in CD4+CD45RA+CD62L+ predicted decreased viremia at the subsequent measurement (OR 0.73 (0.55-0.95)). A similar pattern was seen in the CD8 analyses with increases in the naïve population being associated with decreased risk of viral replication (OR 0.67 (0.50-0.91), p<0.01) and activated cells (CD8+CD38+HLA-DR+) predicting future increases in viremia (OR 1.3 (1-1.7) p=0.05). Conclusion: During follow-up the expression of activation markers on CD4 and CD8 cells decreased, furthermore these markers were predictive of subsequent increases in viremia. Whether the activation markers were induced by lower grades of viremia and hence, were an effect of rather than an inducer of viral replication, remains to be determined.

1. Katzenstein TL et al. Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months. HIV Medicine 2003;4:53-61.