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Jules Levin's TOP 10 STORIES FROM Resistance Workshop
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The 15th HIV Drug Resistance Workshop has always been a key HIV conference each year, during which very often important study results or new leading developments are first discussed. So what were the key topics at this year's meeting.
Merck's new HCV polymerase inhibitor drug: the initial presentation on this drug was at this meeting & showed almost a 6 log reduction in HCV viral load in 7 days in chimps. Merck is ready to implement development & move ahead with studies. As well, Abbott reported on their HCV drug development program, discussing a prototype drug that also appeared potent.
TMC125, the new NNRTI for patients with NNRTI resistance. Tibotec reported new & interesting data that I will be reporting forthright.
TMC114, the new HIV protease inhibitor that is expected to receive FDA approval this June. Tibotec reported several abstracts at this meeting on the drug's unique "pathway to resistance", "genotypic & phenotypic determinants of resistance", and "impact of optimized background regimen on viral response to TMC114".
Two New Protease Inhibitors: PL-100 and SPI-256. Both appear promising. SPI-256 is further along in development & better characterized with early resistance data reported at CROI 2006 & at this meeting; expected to move into patients in early 2007. I reported on this yesterday. PL-100 is in very early development, hopes to be first once daily unboosted PI for naives & experienced. I reported on this yesterday & expanded report coming.
Tipranavir Susceptibility Increased by I50V mutation. Boehringer Ingleheim reported at the Workshop that the I50V mutation is associated with increased susceptibility to tipranavir, and in RESIST studies was associated with greater median reduction in baseline viral load at week 24 (-1.44 log10 copies/mL, n=41) compared to in the absence of an I50V mutation (-0.72 log10 copies/mL, n=58) [P = 0.0345].
20% of Patients Developed NNRTI Resistance in Treatment Interruption in ACTG Study. Viral failure was an increased risk for patients who restarted therapy after interruption with the same regimen.
Sensitive Resistance Testing Detects Low-Level NNRTI Drug Resistance Mutations in Treatment-Naive Patients and Associated With Virologic failure. This was a key topic which received much attention & discussion at this meeting. There was much discussion about whether all treatment-naive patients should receive sensitive NNRTI resistance testing prior to selecting the first HAART regimen. This was a CDC study using their sensitive Real Time PCR sensitive assay. As well, Gilead reported at this meeting that a low-level K65R mutation was found in some treatment-experienced patients using a sensitive resistance test & this was associated with prior ddI or abacir use & L74V/I mutation.
Kaletra Monotherapy Resistance Reported. There was much discussion due to these study results about whether or not Kaletra monotherapy is useful in the developed world & under which well-defined situations might it be useful. At this meeting Abbott reported Kaletra monotherapy resistance developed in two studies, one examining induction-maintenance therapy & the second study examined firstline monotherapy. This development also received much attention. The patient clinical data from these two studies were not reported at this meeting but will be reported at a conference soon.
Tenofovir/FTC combination therapy prevented transmission after rectal HIV exposure in 100% of monkeys in this study. Two ongoing studies, international & in the USA are examining pre-exposure prophylaxis with tenofovir or tenofovir/FTC to prevent sexual HIV transmission. If this approach is effective, this would be a BIG breakthrough. We spend many millions of dollars on HIV vaccine research which has shown no efficacy & there is no promise of efficacy on the horizon. I personally do not think vaccines will succeed & too much money is devoted to this effort.
Protease Mutations Found in GAG. Several studies at this meeting found protease inhibitor mutations in the HIV- GAG gene. The two key questions are: 1- can these mutations be present without the standard protease mutations in previously untreated patients who fail HAART & lead to failure, and 2- in treatment-experienced patients who develop standard PI mutations, does the presence of the GAG mutations amount to additional resistance, are they clinically significant & relevant to resistance.
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