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Vienna Intl AIDS Conference Thoughts from Jules Levin, NATAP
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It's Friday, the last day of the meeting although there is nothing left today to report on data so forth so yesterday was pretty much the last day of data presentations. I tried to get flight out today but was unable so I will have to stay an extra day & leave on my original planned flight for saturday through Frankfurt. The gelato is great here, better than in the USA. Vienna is a very nice city, civilized, old world, much nicer in many ways than NYC or other big US cities, but no Whole Foods and viener schnitzel is not healthy for me nor aging HIVers.
The 2 major stories in Vienna are the once-daily GSK572 data in naives & raltegravir resistance, looks very good for patients certainly in naives but also looks promising for patients with raltegravir resistance, phase 3 studies will tell us more but if a patient is on raltegravir & develops viral failure one must consider stopping so as not to accumulate mutations which can make GSK572 less potent for the patient. The other big story here was the presentation of phase 3 results of the new NNRTI TMC278 which will be jointly developed by Gilead & Tibotec in a once daily 1 pill formulation like Atripla, in this study the percent undetectable was the same as the comparator arm of efavirenz, this was a big study with 1300 patients & 9% viral failures in the 278 group & 4.8% in the EFV group, more nuke (184) resistance (68% vs 32%) and apparently more NNRTI resistance (63% vs 54%) in the 278 viral failures, much less CNS side effects in the 278 arm, better lipids in the 278 arm with hardly any lipids elevations, of interest in the low viral load group (<100k) 278 performed better but in the >100k group EFV appeared to do a little better, when the presenter Cal Cohen was questioned about why by an audience member at the microphone he responded he didn't know why & the company was looking into it, see link to NATAP report of the data.
There were several conference discussions here on aging and comorbidities that were interesting so HIV & Aging is getting wider dissemination, it is truely a global great concern. Older HIVers, over 50 yrs old, who took early ART - AZT mono, d4T mono, d4T+3TC, ddI etc. will have the remnants of muscle wasting, neuropathy, and mitochondrial toxicity, and of course both lipoatrophy & belly fat, all of which will I think definitely contribute much to aging-related problems, such as gait problems, frailty issues, cognitive impairment, heart disease, and probably more. One very interesting study from Todd Brown found lipodystrophy associated with inflammation & frailty, particularly belly fat, this is a must read. Good diet and exercise can help, a very clean mediteranean type diet & vigorous exercise can make a big difference. But I expect mortality to increase as patients age because of the onset of accelerated aging, more comorbidities developing, particularly bone loss & fractures, gait problems, CVD disease, neurologic disease. So the great benefits of longer life & better health we achieved with HAART, will be diminished by this aging affect. WE NEED MORE ATTENTION from the NIH to better address this problem. Plus, aging patients will need more intense & different services including more focused types of care, and this is NOT getting any discussion, like targeted care by specialists-nephrologists, cardiologists, bone experts, diabetes specialists, neurologists etc. There was a lot of discussion here at the conference about cognitive impairment & aging. Yesterday in the Late Breakers the CHARTER Study reported a talk on that CD4 nadir, again the old HIVers who had low CD4 nadirs, is associated with greater risk for cognitive impairment, which they had presented as well last year in Capetown, the presenter also said the amount of time spent with low CD4s probably also might be associated with greater risk but we need to study this, see the NATAP report on this, and patients with undetectable viral load a significant proportion experience cognitive impairment also this was previously reported, I recall the % is 27 or 37%. CHARTER also presented a poster reporting significant cognitive impairment for patients on HAART.
The HIV oral Late Breaker was full of interesting data thursday. The new integrase GSK572 looked very good in naives (phase 2 SPRING Study), potent early viral load declines, called kinetics, 94% <50 at week 16, no safety/tolerability concerns. As well on monday the phase 2 VIKING Study presented results of giving GSK572 to raltegravir failures. The viral efficacy in this study varied depending on the number and pattern of RAL mutations patients had, see the tables below and read NATAP reports for details on all the studies related to GSK572. Here are pics of tables/graphs showing viral load responses in naives in SPRING and between day 1 and day 11 in raltegravir experienced patients in VIKING. We will have to wait for the large phase 3 study to learn more about the responses by patients with extensive resistance. Drug development is on fast track with large phase 3 studies expected soon.
IAC: Raltegravir Resistance Pattern Critical in Early Response to S/GSK1349572 - written by Mark Mascolini - (07/19/10)
IAC: Activity of Next Generation Integrase Inhibitor (INI) S/GSK1349572 in Subjects with HIV Exhibiting Raltegravir Resistance: Initial Results of VIKING Study (ING112961) - (07/19/10)
IAC: HIV Integrase Genotypic and Phenotypic Changes Between Day 1 and Day 11 in Subjects with Raltegravir Resistant HIV Treated with S/GSK1349572: Results of VIKING Study - (07/21/10)
IAC: Activity of the Next Generation Integrase Inhibitor S/GSK1349572 and Two First Generation Inhibitors Across a Broad Panel of HIV Subtype Isolates in PBMCs and MDMs - (07/21/10)
IAC: S/GSK1265744: A Next Generation Integrase Inhibitor (INI) with Activity Against Raltegravir-Resistant Clinical Isolates - (07/21/10)
IAC: S/GSK1349572 Works Fast in Phase 2 Study of Treatment Naive - written by Mark Mascolini - (07/22/10)
IAC: Once-Daily S/GSK1349572 as Part of Combination Therapy in Antiretroviral Naïve Adults: Rapid and Potent Antiviral Responses in the interim 16-Week Analysis from SPRING-1 (ING112276) - (07/22/10)
SPRING Study in naives
The SPARTAN Study reported an early look at unboosted Reyataz+RAL both twice daily, this nuke sparing regimen looked potent but BMS said they discontinued the study at week 24 due to elevated bilirubins -PK was higher with Reyataz BID, RAL resistane emergence for failures, but I think this regimen has good utility for certain patients like ones with metabolic issues, as both Reyataz & RAL are very good on metabolics, lipids. Clinicians I spoke with said often the bilirubin declines with some time if staying on the therapy. Still, another reason I think this regimen was stopped is because future nuke sparing studies will look at darunavir/r+GSK572 and boosted Reyataz+GSK572, which promise to be once daily and effective. Here at the meeting, Abbott reported big study results of Kaletra+raltegravir nuke sparing which looked good, see the NATAP reports. Boehringer Ingelheim reported good looking data on the use of nevirapine in a new once daily extended release formulation compared to the twice daily formulation currently used in the USA, the XR NVP looked as good if not better (80% vs 75% <50), take a look at the report. There was a very good report in the Late Breaker finding the Merck HPV vaccine effective in MSM in preventing anal cancer & AIN, I believe this is the 1st study in men for Gardasil. The first data in a large study of maraviroc once daily was presented in the Late Breakers in combination with boosted Reyataz, the data is interesting and shows efficacy, take a look at the report. Tobira presented data on TBR-652, the CCR2 inhibitor they are developing, see the report, they discuss how the drug appears to help with inflammation. The ACTG reported bone effects from HAART in ACTG5142, and although the results are similar to ACTG5202, in that HAART regimens are associated with bone loss, it is disconcerting. I expect again with the aging population of patients entering their 60s lots of fractures might start occurring, in the general population fractures are associated with mortality particularly in men. There were several interesting presentations on nonAIDS events & cancers occurring more often in HIV+ individuals, one from the CDC, look at NATAP reports.
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