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As CROI 2007 drew to a close, we asked Marshall Glesby, M.D., Ph.D., of Weill Cornell Medical College in New York City to discuss what he felt was the most interesting research presented at the conference.

Well, I'm going to stay away from the obvious things that I'm sure others have commented on, and really just mention a few of the interesting posters that are almost on the quirky side. I'll just start with one by Daniel Fierer, [M.D.] from Mount Sinai, New York [and colleagues]. They looked at a handful of patients with HIV infection [who] had acute hepatitis C that was documented. [They] looked at the results of their liver biopsies and found a surprisingly high proportion of them had advanced fibrosis -- which was certainly unexpected in that, if confirmed in large numbers of patients, it would have major implications [such as] potentially wanting to biopsy people with acute hepatitis C. It may have implications for treatment, as well.

Were there other studies that you thought were interesting?

There was a pharmacokinetic study done by John Gerber and colleagues. He's the senior author, from the University of Colorado. They looked at the statin drug rosuvastatin [Crestor] in healthy volunteers, in conjunction with lopinavir/ritonavir [LPV/r, Kaletra], and found unexpectedly a drug-drug interaction, where exposure to rosuvastatin was increased during the time period that the subjects also took lopinavir/ritonavir. This was an unexpected interaction, and there are potential implications for treating HIV-infected patients, in terms of toxicities, if that isn't kept in mind.

People on lopinavir/ritonavir might have particularly high lipids, also.

Right. I think it's not clear whether we can generalize [about] the other protease inhibitors. The mechanism is not clear. ... I think further studies are needed with other drugs, to see if it's a class effect, or a specific effect.

Very interesting. Any other quirky studies that you came across?

There's one other interesting study that I wanted to mention, in the area of hepatitis B/HIV coinfection by Chloe Thio, [M.D.] from Johns Hopkins [and colleagues], presented as a late-breaker oral presentation today [February 28]. Entecavir [Baraclude] was thought to not have any anti-HIV activity, and many have advocated using it as a drug to treat hepatitis B in HIV-infected patients who don't require therapy for their HIV. Because it's thought not to have HIV activity, there wouldn't be issues with developing resistance to monotherapy with the drug -- HIV resistance, that is.

In this study, they looked at three patients from their clinic at Johns Hopkins who had hepatitis B and HIV. The treatment stories were a little bit complicated. Some of them had had some prior, brief periods of antiretroviral therapy, including with lamivudine [3TC, Epivir], which has activity against hepatitis B as well. But the bottom line is that they noted that these patients actually had about a 1 log reduction in HIV viral load after going on entecavir for hepatitis B. This was unexpected -- and, in fact, they were later able to document data that suggests that entecavir was selecting for the M184V mutation, which confers high-level resistance to 3TC and FTC [emtricitabine, Emtriva] in HIV. It's not totally clear from the data whether the entecavir induced the resistance, or just selected for it. It may have been preexisting based on either transmitted virus or the prior use of antiretroviral therapy in some of these patients. But the data are interesting.

They followed up with some in vitro studies suggesting that potentially entecavir does have anti-HIV activity, which was not previously known. This actually led to a "Dear Doctor" letter from the FDA [U.S. Food and Drug Administration] recently, based on these data. There was some controversy in the question-and-answer session [following the presentation of this research] with a couple of established virologists, including one from Bristol-Myers Squibb [BMS], questioning these findings, and noting that BMS had done extensive studies of entecavir, looking for HIV activity, and found none in their assays. Whether it's a technical difference in the assays done -- whether this is some sort of spurious finding or not -- I think is unclear. I think it's something that merits further study and careful attention if entecavir is going to be used in the absence of HIV therapy in people with hepatitis B/HIV coinfection.

Is it often used in the absence of HIV therapy?

Well, it's a relatively new drug, so I don't know [that it's] necessarily in wide use, but since most of the drugs that we think of using for hepatitis B also have HIV activity, if we want to treat just hepatitis B alone and not treat the HIV, then there are really only a limited number of drugs. Entecavir was on that list. Potentially adefovir [Hepsera] at low doses, though I think it's not totally clear. It's thought that it won't have anti-HIV activity at the low doses used for hepatitis B, but I don't know how carefully that's been studied. And interferon, which I think people are loathe to use, just because of its tolerability issues.

To read or listen to more interviews with HIV clinicians about what they felt was the most important research presented at CROI 2007, click here.