HIV-DNA in PBMC, a marker for disease progression

Ch. ROUZIOUX1, J-B. Hubert, C. Deveau, M. Burgard, M-L. Chaix, C. Goujard, J-F. Delfraissy and L. Meyer  for the SEROCO and the PRIMO ANRS Study Groups.

1Laboratoire de Virologie, Hôpital Necker, EA 3620 Université René Descartes, Paris (France)

can Latent HIV persists in resting memory CD4+ T cells, even after efficient HAART. The stability of this latent reservoir has been reported by different groups showing an extremely slow decay in patients on HAART.  Although it is generally recognized that quantification of HIV DNA in PBMC is important in patho-physiological studies, it remains unclear how this marker could help monitoring disease progression. Numerous studies performed in our lab in different contexts of HAART treatment indicated that HIV DNA could represent an informative marker in addition to HIV RNA; we also observed that levels of HIV DNA appear to be different among patients. Such results have raised questions about the predictive value of this marker for the risk of progression to AIDS in comparison to HIV RNA in plasma and CD4+ T cell count.

The French SEROCO cohort study which started in 1986 provided the opportunity to look back at the natural history of HIV infection by assessment of the level of HIV DNA in peripheral blood cells and its consequence in term of disease progression. Frozen cells samples of 383 seroconverters followed for more than eight years before the HAART era were tested for HIV DNA levels in PBMC using DNA-PCR (the assay measures all forms of intracellular HIV DNA most of which is proviral DNA). Our results show that HIV DNA level was a major predictor of progression to AIDS and death, independently of HIV RNA levels and CD4 cell count (adjusted risk for 1 log increase: 3.2 (95% CI: 1.7-6.0).

In the French PRIMO cohort study, patients are included at time of HIV primary infection, HIV DNA has been quantified in samples taken in the first weeks after infection. The results indicate that HIV DNA levels seem to be established soon after infection and present a relative stability over time, in untreated patients. Our data suggest that HIV DNA in cells and HIV RNA in plasma have different merits assessing the risk of disease progression: HIV DNA measurment reflects the global level of the stock of latently infected cells able to produce virus, while HIV RNA is more related to the viral fitness and reflects the active ongoing viral replication.

In conclusion, different studies including ours have reported the high predictive value of early levels of HIV DNA in PBMC. New technologies such as PCR in real time may facilitate large studies of this marker and permit to explore its role in clinical practice.