05/20/10

PRN Report: Dynamics of Viral Decay in the Treatment of HIV Disease: Does Speed Matter?

Does the speed, or decay rate, with which antiretroviral medication clears HIV affect long-term clinical outcomes? This question has been asked for many years as new treatment options come along, but now with the introduction of raltegravir, which causes viral load to plummet faster than any previous agent, PRN invited Dr. Daniel Kuritzkes on May 18 to discuss results of ACTG study A5248 comparing viral decay rates and clinical outcomes of raltegravir- vs. efavirenz-based regimens in treatment-naïve subjects.

In this study, the raltegravir arm demonstrated a higher proportion of undetectable viral load, earlier than the efavirenz arm, due to what is described as a bi-exponential decay model in which the first phase of decay (d1) dominates for a longer period of time and extends to a lower HIV RNA level. But raltegravir also blocks the transition of cells in a state of “pre-integration latency” into productively-infected, slower decaying cells, thereby reducing the pool of cells that contribute to the second phase of decay (d2). Future analyses will look at pharmacokinetics, single copy HIV RNA assay, integrated and unintegrated proviral DNA, and CD4+ T-cell restoration.

Dr. Kuritzkes concluded his review of this study stating that while the faster viral decay rate associated with initiating a raltegravir-based regimen reflects the mechanism of viral suppression which is determined by drug class and location of antiviral activity in the HIV life-cycle, this does not necessarily predict better long-term viral suppression, and that to date, no study has shown a clinical benefit of faster viral decay after ART initiation. And while more rapid viral decay might be beneficial in pregnancy or primary infection, there are still no data to support this concept.


Reference: Daniel R. Kuritzkes, MD (Section of Retroviral Therapeutics, Brigham and Women’s Hospital, Harvard Medical School). Dynamics of Viral Decay in the Treatment of HIV Disease: Does Speed Matter? Presented at the May 18, 2010 meeting of the Physicians’ Research Network (PRN); New York, NY.

Source: Reporting from New York City for PRN News: Jim Braun, DO