Overview of Resistance Workshop in San Diego June 23-26

Here is a brief summary of additional selected highlights from the Resistance Meeting which just finished yesterday in San Diego. As soon as I arrive back in NYC I will write a comprehensive review.

Preliminary new data was reported for several promising salvage drugs-

ABT-378 is a new protease inhibitor. Individuals who failed one PI, were NNRTI naive and some of whom had in vitro cross-resistance to other PIs received 378 received ABT-378, nevirapine, and at least 1 new NRTI. The data is reviewed in detail on the NATAP web site. After 24 weeks 83% using an as treated analysis and 77% using an intent to treat analysis (non-completers equal failures) had <400 copies/ml.

Tipranavir is a new PI. Researchers presented promising in vitro resistance data showing that tipranavir was effective in suppressing HIV resistant to Pis. Again the NATAP web site has a comprehensive review of the data. Studies are starting now to explore this drug in People with PI resistance.

DAPD is a new NRTI which also shows to be effective in vitro against HIV resistant to NRTIs. In preliminary data in treatment-naïve humans it looks to have potentantiviral activity.

RS-344 is a new PI being developed by John Erickson at the NIH. For a couple of years he has been talking about his hope to develop a PI which would be effective against the most problematic primary PI mutations. He believes he may have developed one in RS-344.

T-20 is a fusion inhibitor. The manufacturer, Trimeris Inc, has developed a second generation fusion inhibitor T-1249. Previously they presented data that T-1249 was more potent than T-20 in vitro and active against T-20 resistant virus. At this meeting they presented preliminary data showing that T-1249 suppressed HIV resistant to T-20 from humans in their 003 study.

AG1549 is a new NNRTI from Agouron which may be effective against HIV resistant to NNRTIs with the K103N mutation. This mutation is the key one causing resistance to efavirenz. Human studies for this drug are starting .

Resistance Testing

Several studies were reported correlating genotypic test results with phenotype test results. The data remains preliminary but promising. This means you could get use a genotype test and get results back more quickly. Virco reported on the large database they’re building correlating the results of these two tests.

Preliminary data from two studies testing genotypic testing have been previously presented—Viradapt and GART. Additional data was presented at this meeting holding up the data that genptypic testing can resultin better viral load reductions from a regimen selected with genotypic testing. However, it is crucial to be careful in interpreting results from resistance testing. Interpretation requires a certain expertise and knowledge in understanding resistance and mutations related to certain drugs and combinations of drugs. The resistance testing manufacturers are planning educational efforts for doctors and patients. Telephone hotlines are being considered to help patients and doctors interpret results. NATAP is planning an educational symposium for doctors (CME credits) on understanding and interpreting resistance test results in NYC for July 29. Please contact our office if you are interested in more information.(212 219-0106).

In the summary of the Resistance Meeting John Mellors the researchers expressed that they felt it is still premature to recommend resistance testing be used standardly in clinical precatice. More wrinkles need to be worked out. But if and when they are resistance testing is expected to be an important tool for making treatment decisions. It should be used only as one of several tools in making treatment decisions .

Prevalence and Transmission of Resistant Virus

It appears as though transmission of resistant HIV is modestly increasing . Researchers discussed this subject with concern nat this meeting. Of particular interest is the finding of in vitro NNRTI transmitted resistance. Researchers from various parts of the world reported increased incidence of this but it remains uncertain if this in vitro resistance will translate into reduced clinical response because most of the detected resistance is based upon polymorphisms and not primary NNRTI mutations. It is crucial for people to protect them selves from contracting resistant HIV through IV drug use, sax, etc. The researchers suggested an international collaborative to characterize the true extent of the problem.

Immune Reconstitution

Researchers are trying to characterize the true extent and reasons for CD4/HIV-RNA discordance. This is where CD4s stay elevated despite viral load rebound. Ir was suggested that this may be due to reduced viral fitness from PI therapy. Nonetheless, one researcher reported that CD4s start to decline after about 2 years. It is uncertain how often this occurs—where CD4s remain elevated after pVL rebound.

The hot topic of drug interruption was discussed. Several studies are starting exploring the possibility that a person with undetectable HIV could interrupt therapy, elicit an immune response, and have the immune system control HIV without drug therapy. Several promising but very preliminary data were presented at this meeting that such a possibility may develop. But it is way premature to do this on your own. The long term effects of reseeding tissues that had low VL due to HAART are unknown. The latent reservoir for HIV may be replenished if drug therapy is stopped. One study will explore IL-2 + HAART in approaching drug interuptions. It’s possible several interruptions may be successful. But resaerchers do not understand yet how to accomplish this and why some individuals may respond while others don’t. I'll report details of the study presented here in a follow-up report as soon as I return to NYC.