Studying Viral Evolution During HAART and Modeling HAART in Animals

The last two days of the conference saw promising news for eradication research. Yesterday, Sarah Palmer from the Karolinska Institute in Sweden reported that she and her colleagues compared single HIV RNA sequences from plasma taken from eight patients just days before they started HAART, with sequences of single integrated proviral HIV DNAs in T cells from the same patients’ blood and gut associated lymphoid tissue (GALT) taken between four and ten years later.

She found no difference in the kinds of sequences found in the samples taken from the same patients shortly before they started HAART and years later. This suggests that in people on HAART, there is no sequence evolution in peripheral blood and GALT, which in turn suggests that there is little or no residual viral replication. She also found that most cells only harbor one integrated HIV DNA.

This is good news for HIV eradication efforts, Palmer said, in that "if you have to purge the reservoirs, you don’t have multiple HIV molecules that have to be purged. And we don’t have continual reseeding of the reservoir, so hopefully once we purge this reservoir, it’s not being reseeded as long as you stay on HAART.”

Good news also came from two speakers today who reported that it now seems to be possible to mimic HAART in nonhuman primates by bringing down plasma viral loads to undetectable levels. Binhua Ling from the Tulane National Primate Research Center said that she and her colleagues succeeded to reduce viral load levels of SIVmac239 in chronically infected Chinese rhesus macaques to undetectable levels of less than 30 copies per ml of plasma using a combination of three ARVs.

Jeffrey Lifson from the National Cancer Institute in Frederick also achieved this with a combination of several ARVs in SIVmac239 infected Indian rhesus macaques, which when untreated typically show higher viral loads than Chinese rhesus macaques and are considered one of the most difficult models to achieve repression of viral replication. Lifson and colleagues are also treating their animals with the histone deacetylase inhibitor SAHA to see if that can reactivate replication of latent SIV in these animals.