New HIV Regimen Outperforms Gold Standard

[arlo 0]

http://www.medpagetoday.com/InfectiousDisease/HIVAIDS/dh/2512

**Advise interested patients that current treatment guidelines suggest that either regimen can be used to initiate treatment for patients newly diagnosed with HIV and not previously treated with antiretroviral drugs.


**Note that this study suggests that the regimen of Viread (tenofovir DF), Emtriva (emtricitabine), and Sustiva (efavirenz) is more effective and less toxic than Sustiva plus AZT and 3TC (zidovudine and lamivudine).


**Specifically note that the risk of lipoatrophy appears to be less with the newer regimen.



Review
BALTIMORE, Jan. 18 - A simple once-a-day HIV antiretroviral regimen does a better job of suppressing the virus and restoring immune function than the long-standing gold standard for initial treatment of HIV, according to investigators here.


The new kid on the block is a combination of Viread (tenofovir DF), Emtriva (emtricitabine), and Sustiva (efavirenz). In the first year of a three-year randomized trial, it proved significantly more effective and less toxic than a regimen consisting of Sustiva plus AZT and 3TC (zidovudine and lamivudine).


The Viread/Emtriva/Sustiva combination did a better job of reducing viral load and increasing CD4 cell counts, Joel Gallant, M.D., associate director of the AIDS Service at Johns Hopkins here and colleagues reported in the Jan. 19 issue of the New England Journal of Medicine.


Both regimens are recommended in current treatment guidelines as possible first choices for treatment for a person newly diagnosed with the virus, but this is the first head-to-head analysis comparing the two, he said. The results of the study will "drive new prescribing" for patients newly diagnosed with HIV, Dr. Gallant predicted.


Also, he said, fewer patients treated with the regimen withdrew from the study because of adverse events, although overall the same proportion of patients in both arms reported unwanted side effects.


"The number of people who dropped out of the study because of side effects was significantly different," Dr. Gallant said, "and that's what drives the difference in efficacy."


Dr. Gallant and other members of the study group reported that they have consulting fees, lecture fees and grant support from the makers of the some of the drugs in the study, while other members of the study group are employed by Gilead Sciences, which makes Viread and Emtriva.


The researchers enrolled 517 treatment-naïve HIV patients and randomized them, in an open-label fashion, to one of the two combinations. The primary endpoint was the percentage of patients who were able to maintain fewer than 400 copies of viral RNA per milliliter of blood.


Secondary endpoints were the proportion whose viral load was less than 50 copies per milliliter of blood, differences in CD4 cell counts, and the proportion of patient who stopped treatment owing to adverse events.


The study was designed to show that the Viread/Emtriva/Sustiva combination was not inferior to the other regimen, but in fact, Dr. Gallant said, the study showed it was superior:


84% of patients in the Viread/Emtriva/Sustiva arm were able to maintain a viral load of less than 400 copies, compared to 73% on the other regimen. The result both excluded inferiority and was significantly better at p=0.002.
80% of patients in the Viread/Emtriva/Sustiva arm had a viral load of less than 50 copies, compared with 70%. This also excluded inferiority and was significantly better, but at p=0.02.
Patients treated with Viread/Emtriva/Sustiva had a mean increase from baseline of 190 CD4 cells per cubic millimeter, compared with 158 cells for patients in the other arm. The difference was statistically significant at p=0.002.
Only 10 of the 257 patients in the Viread/Emtriva/Sustiva arm dropped out owing to an adverse event, compared with 23 of 254 in the other arm. The difference was significant at p=0.02.
The main reason for dropping out was severe anemia, experienced by 14 patients in the AZT/3TC/Sustiva arm and none in the Viread/Emtriva/Sustiva arm.

A common problem in regimens containing AZT, Dr. Gallant said, is so-called lipoatrophy - fat redistribution that significantly changes the body shape of the patient. In this study, patients in the Viread/Emtriva/Sustiva arm had significantly more limb fat at 48 weeks than those in the other arm.


Unfortunately, he said, baseline data on limb fat was not collected, making it difficult to quantify changes. However, a preliminary analysis of 255 patients who have been treated for 96 weeks suggest that the difference persists and may increase over time, he said.


If so, that may prompt some patients who are currently doing well on AZT/3TC/Sustiva to switch.


A central factor in long-term suppression of HIV, Dr. Gallant said, is the ability of patients to follow sometimes complicated drug regimens. Both of the regimens in this study, however, are relatively simple, although the edge goes to the Viread/Emtriva/Sustiva combination, which can be taken once a day.


The Viread/Emtriva combination is now available as a single pill, dubbed Truvada, which reduces the so-called pill burden to two a day. AZT and 3TC are also formulated as a single pill, Combivir, but are taken twice daily, while Sustiva is taken once daily.


Dr. Gallant said the advent of the Truvada combination has increased the popularity of the Viread/Emtriva/Sustiva combination; a further simplification is expected soon, in which Sustiva will be combined in a single pill with the other two drugs.


"We'll have gone in 10 years from some incredibly complex and toxic regimens to one pill once a day that's relatively non-toxic," he said, "which I think is certainly a sign of progress in therapy."


Primary source: New England Journal of Medicine
Source reference:

[SpeedRacer 1]

Interesting. Although the treatment focuses solely on Reverse Transcriptase Inhibitors. Also the study was performed only on treatment-naive patients, so they're less likely to have resistant viruses.

I wonder how this treatment would work if combined with a protease inhibitor.

Speed Racer
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[arlo 0]

how skewed do you think this study (and publication of study results) really is? i see this stuff and post it simply because i think it may inform some people (someone may have friends or family recently diagnosed), but having folks like yourself that have worked directly in this field definitely will help lend credit to or discourage some of the stuff that's put out by these studies.

are these types of studies as skewed in the medical industry as the media does "everyday" stuff?

what i got from this is that folks that are HIV positive who have never received treatment before may now have an alternative to the "old standby." i guess my line of thinking is that even having an alternative is better than nothing - hence the post.
(and thanks for your work in the field. i don't know anyone personally that has HIV, but i think i'm in the minority there. )