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120 HIV Persistence Challenging Therapeutic Success

Lafeuillade, Alain

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 48
doi: 10.1097/01.qai.0000397308.71470.33

General Hospital, Toulon, France

HIV integrates in host cells, in particular in a pool of latently resting CD4 cells with a half life of several decades. Despite the availability of 30 different ARVs to block viral replication at different steps of its life cycle, this reservoir rekindles infection each time therapy is interrupted. In fact, HIV RNA persists at a few copies/ml in the plasma of patients under effective combination therapy. Whether these low levels are the result of cryptic replication or the release from previously infected cells, remains debated. Intensification trials have failed to show any effect on these residual RNA levels. However, a recent study found an increase in 2 LTR circles and a decrease in activation markers in about 30% of raltegravir intensified cases. In another study changes, although not significant, were only found in ileum biopsies, raising the possibility that events in plasma doesn't correlate with those in tissues. The origin of this persistent viremia is not clear, and the contribution of different cell types, including haematopoietic progenitors, has been proposed. It is also possible that some anatomic reservoirs are involved. However, sites like the central nervous system more probably act as sanctuaries, with the observation of a high prevalence of neurocognitive disorders, even in ‘successfully’ treated patients.

Another negative aspect of HIV persistence despite effective viral control is the presence of abnormal inflammation in most patients and its consequences in terms of increased atherosclerosis and premature aging.

Finally, even if ARVs are currently less toxic, long term side effects remain frequent like lipid, bone density and renal function alterations.

Consequently, as patients suffer from the added penalties of progressive infection in some compartments, collateral effects of inflammation and drug toxicities, the search for a cure remains a realistic goal even.

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.