Researchers Study the Effect of HAART on Eradicating HIV Reservoirs
by Chael Needle

[Treatment Horizons]

In the January 2 issue of AIDS, French researchers, led by Dr. Jean-Paul Viard, suggest that HAART suppresses but does not appear to diminish HIV reservoirs. Not so long ago, research suggested that HAART could possibly empty the reservoirs, but HAART seems to only most effectively work while the virus is actively producing. These hard-to-identify reservoirs are made up of HIV-infiltrated T cells (and perhaps other cells) which are resting, that is, not actively completing infection. If and when these cells become activated, however, infection can be completed. That means that even though a patient’s viral load may be undetectable, reservoirs of HIV may still be lying in wait. The eradication of these reservoirs might mean the difference between the management of HIV and its cure.

The impetus for the study, says Dr. Viard, came from the pioneering work of Professor Christine Rouzioux, who is the head of the virology lab at Hôpital Necker in Paris, France, the same institution where Dr. Viard is the head of the HIV unit in the infectious diseases department. Specifically, that work has focused on “the measurement of proviral DNA (the HIV DNA that is integrated into cells) as a way to look into the viral reservoir.” He continues: “This work was the first to show that HIV DNA has a prognostic value, complementary to but independent from plasma RNA [viral load] and CD4 count [as markers of HIV progression and suppression]. So, naturally, the question of whether proviral DNA is influenced by HAART in the long term was one we wanted to address.”

Viard and his colleagues studied forty-one patients who had a constant undetectable HIV RNA load from within six months of HAART initiation. Participants were outpatients seen in their department who were sampled for DNA since they began HAART. They were studied retrospectively for a median of about five years. The research team measured viral reservoirs by “the quantity of HIV DNA associated with peripheral blood mononuclear cells [PBMCs]. This is done using a polymerase chain reaction, very much like the one that is routinely used for the measurement of plasma viral load, except that this time we amplified DNA associated with cells and not RNA found in plasma.”

Testing in twenty-five patients showed a decrease in HIV DNA in these PBMCs during the first year, lesser reductions in the following two years, but no significant drop thereafter. This seems to indicate that the reach of HAART is limited. Other research suggests that while HAART cannot eradicate reservoirs by itself, it can possibly restrict the expansion of latent HIV reservoirs, especially when HAART is combined with Interleukin-2.

There has been talk of identifying reservoirs through HIV proteins, and also flushing reservoirs with Peptide T. “‘Flushing’ the reservoirs is a nice idea but how you do it has not been found,” says Dr. Viard, whose research interests include autoimmune diseases and HIV infection, particularly immune restoration, long-term effects of treatments, metabolic side effects of antiretroviral drugs. “My bet would rather be that the measurement of the HIV reservoir will be used as prognostic tool, particularly for deciding treatment interruptions.”  As for next-steps in research, Dr. Viard suggest that this work is complemented by similar investigations into therapeutic protocols such as immune-based therapy. More research, of course, is needed to explain the mechanisms of HIV reservoirs—especially in this age of drug resistance mutations—and their ability to persist.

Chael Needle wrote about the potential therapeutic effects of marijuana on neuropathy in the March issue.

April 2004