| I
am amused at the display of ignorance. I thought everything was
hirschmans fault but I hear Hawkins feels differently. Funny. Wilner was
boondoggled and lied to. I understand the board had no interest in
seeing hirschman step down. He did so in favor that nowinski blew smoke
that he could not deliver on. Looks like Wilner is predisposed to
misguided and selfishly abusive shareholder. Too many lies! I smell
Wilner doo doo. The proof is out. The HPV shelf. The focus on cachexia
versus HPV. I think you need to determine if you fully understand how
and why. I do. The chip and shoulder has been discovered. Bregman lost! |
| Count.
Last game play was that Bregman and Wilner and Nowinski claimed that
Hirschman bungled HPV based on overlooked Argentina data. Well? Hawkins
must be blind right? LMAO Last game was that PPS was Hirschmans fault. Well? With insiders selling, how do you feel? Another Wilner/Bregman blunder. Wilner needs to learn that when you retire an old fart, you don't bring him back because he has old expense reports and lost arguments buried in Argentina politics. You catching on now? |
| yanks, I have been here a long time. I have never taken sides but have tried to remain objective. I don't care who is right or who is wrong. I want to see the drug complete an approved trial. I, of course would like the drug to work. At this point I just want to know if there is one Governing Body that will allow AVR 118 to be sold. That is what I care about. In the interim we can trade, we can pizz and moan, we can vent or praise, I don't care. I join the discussion. I am glad to read what you have to say. One exception, I wish the nasty stuff could be eliminated. We called once, as I recall what was said was unimportant to what has transpired. (Voluntary Disclosure: Position- Long) |
| thx.
I never felt you had any other agenda. You are one of the very few
participants I read. I did not see your post to me as an argument. My
comments are focused on what I feel I believe and know. I did invest
time to understand the opinions from both sides. My view is based on
merit. It is just an opinion. We all know what opinions are like, and
everyone has one. There is a dramatic difference in the value of
opinions. Those derived based on preference or bias can yield a colored
value. Those observed from a neutral position may be uncolored. This thread? Little value. My opinions, little value. But uncolored without agenda. I want to see success. All the other noise here can be separated. I like that.
|
||
| The
old Antigenics, Inc. biography of Elma said she had brought three
anticancer and anti-infective drugs to market in previous positions. The
drugs were not named. |
Hawkins
is very lucky to walk into a situation where the drug is technically
developed. No research required. It's like being born and the doctor
giving you your life result without the need to face adversity,
education and scrutiny. Born with the key to the universe. Thank you
God. We are blessed. Let's hope the drug works. It's never a one person
success. Old Bregman propaganda machine generated sour milk. Sour milk
in face reveals a developed product with an ASCO meeting and trial data.
That process started long ago before D'Olimpio. No rhyme intend. Let's
watch. I think my picture is unbiased. it was the board members, wilner,
friedland and the large investors that wanted Bregman to retire. The
same large investor posting here who claims the opposite. Time for the
sour milk cannon to be emptied. The Doctor gave the newborn the key to
the universe. Right? I am sure Bill Bregman agrees.
|
||
| Do
you know if the reason Carol Armenti left the scientific advisory board
during the Nowinski debacle was because of the shelving of the HPV Phase
II testing. She was/in, of course an advocate for women's health and the
founder and Executive Director for the Center for Cervical Health, a
patient advocacy organization primarily devoted to cervical health
issues in the U.S. - and I would assume it would have incensed her to
see this put aside. I also know Nowinski told SZH that the canceling of the HPV trails was a HUGE mistake. Which is why I am AMAZED that they are now choosing to stake ADVR's future on some sort of "fast track" attempt with a NEW INDa, when they already have the go-ahead to begin HPV testing IN THIS COUNTRY WITH DATA THAT THE FDA _WILL_ ACCEPT!! |
| Very
solid comments! All I know is that the decision was made because HPV
cannot gain revenues for advr as rapidly as the more important issues
and values the drug can provide. Count how many years Weizmann and
Selikoff have been involved. Do you see them in HPV? Wasn't HPV the
Bregman agenda? You should probably inquire why Armenti is not there.
Did she fit in? Nowinski? What did the board think? All I see has been
Hirschman push to cancer, hiv. The old company pushed HPV. - - - - - |
| "All
I know is that the decision was made because HPV cannot gain revenues
for ADVR as rapidly as the more important issues and values the drug can
provide." It's NOT how MUCH revenue will be produced, it's about producing ANY revenues at all. Had ADVR done the right thing early on (and by this I mean when we still had contacts in Latin countries that SZH quashed), we might never have had to go to the vulture financiers over the last years - which in my opinion put the PPS where it is. |
| "Do
you think Hawkins would prefer to go to Latin countries? She could get
quicker revenues there right?" ----------------------------- Probably not now - but early on when ADVR DID have those inroads there, any cash generated there could have been used to help finance the US approval. It was an opportunity (of many) missed when SZH came aboard - forgetting about WHO was in control as whether it was a good idea or not. I have always maintained, as I am sure YOU know, we lost valuable time (and potential cash) when we summarily discontinued talks with the Mercatur countries in the mid-nineties. Though I probably consider Hawkins more "in-the-know" insofar as moving a drug through the FDA process (than SZH was/is) - her tack of starting anew again with a NEW attempt at an INDa reminds me of paths taken by SZH when he disbanded ALL venues for potential revenue in lieu of a new IND proposal. With a HPV Phase II just sitting there (assuming the testing done to this point is healthy and positive enough) waiting for SOMEONE/ANYONE to start it up, it seems counter-productive to ditch that and start anew - hoping the FDA will grant fast track status. At the very LEAST, Elma owes it to shareholders to explain IN DETAIL why they have not chosen to go forward with the Phase II HPV tests. - - - - - |
| I
said before that I agreed with the need for revenues. I raised the issue
of HPV and hirschmans development, nowinski, because firehirschman
stated that the board demanded it when hirschman actually stepped aside
in favor of a nowinski opportunity, nowinski did not demand that. The
propaganda machine claimed it was because bregman claimed the missed
opportunity via firehirschman. And now you are wondering why Hwakins
feels the same way hirschman did. The facts are the facts. - - - - - View Replies » |
| It
was Globomax who decided on HPV..... Consider.....that they have some cumulative of many, many more years experience with the FDA than Hawkins will ever have if she lives several lifetimes..... They spent 2 years studying Product R, and I am convinced that the decision to go forward to the FDA with an IND for HPV was well thought out..... It was the most efficient route to an NDA and a revenue producing drug !!!..... To go forward at this juncture with an injectable is going to be a hard sell to the FDA.....And, ADVR will have to come up with at least 10 times the 12 million that they are getting form the Dicke's in quarterly installments..... JMO.....-kevtod |
| See
now yanks that is where a reasonable discussion can be engaged. It could be argued that although HPV as you write, "cannot gain revenues for advr as rapidly as the more important issues.." by April 0f 2004 (already past) ADVR would be a full 2 years into the FDA approved HPV trial. Some questions might include two. How far along the approval process would we be? Would the process have attracted partners? Then a few thoughts. If things went well it seems logical it would be approved before anything that isn't even started yet. Once approved it would generate some revenue and most importantly AVR 118 would have gained recognition. I for one think they made a mistake not to go ahead with the HPV Trial. The part that got me upset is the PR that informed us they were going ahead. That hadn't even located sites to perform the work. I took 4 or 5 months for the PR that told us they were not going ahead. That info was included as a rider in the Kent PR. If I am not mistaken the old intro to the website said 5,500,000 new cases were found each year. Seems like a solid patient base versus being unable to find 30 patients in Israel. There is also the issue about who ordered dropping the HPV Trial. It was April of 2002 when we were told HPV was a go. The Kent announcement was 9/25/2002. In that one we were told HPV was dumpped. But it was not until 8/28/2003 that we read this, YONKERS, N.Y., Aug. 28 /PRNewswire-FirstCall/ -- Advanced Viral Research Corp. (OTC Bulletin Board: ADVR) announced today that Dr. Shalom Z. Hirschman has stepped down from the position of CEO, President, Chief Scientific Officer and a director of the company in order to devote his full efforts to the office of Chief Scientist for the company with responsibilities as assigned by the Board. So that means both the starting and the stopping of the HPV Trial came under Dr. Hirshman's CEO watch. Importantly Dr. Hirshman was also COB when the Trial began. He must have wanted it, he was CEO and COB. Wilner took over as COB 8/13/2002. So Wilner was COB when the announcement was made to discontinue. So if my dates are correct how does that square with your comment, "All I see has been Hirschman push to cancer, hiv. The old company pushed HPV."? I just think reasonable people could agree there is value in both opinions. (Voluntary Disclosure: Position- Long) |
| "The
facts are the facts" --------------------------- You must mean YOUR facts are YOUR facts, don't you?? Without knowing WHO you are and WHAT your relationship is with ADVR and its BOD, everything you say here must be taken with a grain of salt, as I am sure you understand. Much of what you post is fairly inside information (perhaps not in the legal definition though) and it is most assuredly interesting. However that said, no one can attest to the truth of anything YOU say here. That is, unless you choose to reveal your credentials and identity so that we can properly evaluate the validity of your claims. Needless to say, what I say here comes from heresay and I am willing to acknowledge that. I feel that Chuck Miller had IMPORTANT connections in Latin countries (and elsewhere) that would have generated income for ADVR for the impending IND application - had SZH not interfered and discontinued them. Take it for what it's worth - as I will what your reputed claims here. Truth in advertising, I say, and thus far without knowing who your are, you have failed that particular test - as well as any information you post here. - - - - - |
| Shalom
Z. Hirschman-"The Company is now beginning Phase 2 of this IND
process. It is our objective to bring Product R into the pharmaceutical
marketplace as quickly and as efficiently as possible". "the
company now is beginning Phase 2 clinical trials by recruiting clinical
sites".?????? (Voluntary Disclosure: Position- Long) |
| Pfizer
to buy more biotechs in strategy change May 3, 2004, Financial Times Pfizer says it plans to shift from a strategy of licensing and partnering to one that will have it acquiring a good number of biotechs to help pad its pipeline as it preps for 2007, the year patent protection of Norvasc, Zoloft, Zithromax and Zyrtec ends. Chairman Hank McKinnell: "The one change you will see in this area is us doing a lot more acquisitions." The article: "Most biotechnology groups want licensing deals but Mr McKinnell believes the tough climate for small research-based companies will lead to agreements becoming acquisitions." |
| makes
sense to get your foot in the fda door so to speak with the hpv, then
once you know how the fda works, and the fda knows you and how the drug
works it would be easier to go the next step with them for the
injectable, you learn to crawl before you learn to walk and you walk
before you can learn to run.....why can't they figure this out after 10
years |
| Assuming
the financing is there & in order.... IMO- Topical for HPV (and this of course assumes that the drug proves it's efficacy thru the trials) could go from IND approval thru Phase III, and to market within 4 years.....5 years maximum......JMHO.....If we go into Phase II now, 3-4 years..... Injectable for any indication ???? Who knows ???? IAG.....-kevtod |
| Given
the drug's IND history with the FDA, the agency will also want to know
the reason why the HPV trials were suspended after the successful
completion of Phase I and an indication of "all systems go" by
the company for the Phase II trials in early 2002. The FDA will review
the past filings fom the company and their status when the new
injectable IND is presented to them. |
| Thx.
Do you think a candidate with superior short term results in phase 2
would garner the FDA's view and possible vote for fast tracked status?
If this is the case, can you describe the current market size and the
demand for competing products? Is your opinion that the risk/reward
benefit with HPV outweighs the current strategy outlined by Hawkins? Do
you think a focus on cachexia warrants a better r/r ratio? Do you think
this result created an impact on development strategies? thx. |
| The
decision to go with HPV for the first IND was initially made in
consultation with Globomax for the following reasons: The drug supposedly did very well when topically applied to genital warts in clinical trials in Argentina. A research finding made by ADVR scientists, which was presented at a national conference, showed that the drug did something to the humanpapilloma virus oncogene, according to a press release at the time. It was thought that a topical use of the drug would be easiest and quickest to get through the FDA as the rules are much less stringent than for an injectable. If the drug could be marketed as a topical, physicians would become aware of the drug and its immunomodulating effects, and its lack of toxicity would be noted clinically. That could then open the doors to injectable uses of the drug. Though the size of the market for topical drugs against genital warts is not huge, it would allow Advanced Viral Research to generate sales, obtain revenue and establish credibility as a pharmaceutical company. The lack of toxicity and skin irritation of AVR118 could be a major advantage and selling point for the drug against the other drugs already on the market for topical treatment of genital warts. Given all these positive attributes for persisting with HPV, both Hirschman and Hawkins seem to have shied away from continuing these trials. This could possibly be due to two factors- Repetition of the topical genital warts studies in patients in the US or elsewhere may have failed to replicate the spectacular results seen in the original Argentina studies (which may or may not have been carried out under controlled conditions, or to FDA standards). The preponderance of cancer specialists and particularly, a cancer cachexia expert (D'Olimpio) on the Scientific Advisory Board may have suggested opting instead for applications of the drug in cachexia patients, which then led to the three original cachexia trials in Israel. Since company funding was limited, the HPV trials were left by the wayside. The reasoning may have been that the patient base and market size was much larger for AIDS and cancer cachexia, and that trials and possible first approval of the drug in Israel could also open up marketing the drug in Europe. |
| funny,
i have heard the words "fast-trac" so many times over the
years they have lost any meaning at all as it pertains to advr. it's a
sick dream she shouldn't even have mentioned. HPV might have possibly
made it to market in two years (from now). revenue, partner, might have
been a possibility in the forseeable future given the remarkable claims
of efficacy with no side effects by the company over the years and a
total concentration on that application. now, here we sit with a new ceo
with a new plan. gooooooo advr (Voluntary Disclosure: Position- Long) |
| funny,
i have heard the words "fast-trac" so many times over the
years they have lost any meaning at all as it pertains to advr. it's a
sick dream she shouldn't even have mentioned. HPV might have possibly
made it to market in two years (from now). revenue, partner, might have
been a possibility in the forseeable future given the remarkable claims
of efficacy with no side effects by the company over the years and a
total concentration on that application. now, here we sit with a new ceo
with a new plan. gooooooo advr (Voluntary Disclosure: Position- Long) |
| I
guess you are acknowledging there are no guarantees.I thought she was
the new found life for advr? This is what Bill Bregman and BarryAllen
and fireboy has proclaimed. I think you are saying she has the key and
let's see if she can handle it? You are making me wonder why Bregman
made Hirschman out to be a Nobel Prize winner? Guess that makes Wilner
look like a MBA wannabee. Just kidding. Crazy. - - - - - |
| It
appears that you are assuming one individual is responsible. I think
that is the point I offered. It's not my opinion that was the case. I am
not interested in a debate. I just value the opportunity to share my
opinions here. When I say I know enough to draw an opinion. I am stating
that the information and facts and rumors I gather allow me to determine
what I know. What I know is my opinion. Thx. |
| Well
at least it's no longer the issue of a country looking for a drug. I
forgot. The China distributor has a patent in his venue of interest.
Which poster said that again? mbengineer? |
| "advr
has some extremely talented individuals on its scientific advisory team.
HPV sideline must have been calculated." The ostensible reason was simply, "We don't have the cash!"" This was NOT a scientific decision, so the "scientific advisory team" should have had no input whatever to the discontinuation of trials, Unless, that is, there is more to it that cash related problems. - - - - - |
| EVEN-
The topical IND cost over $5,000,000..... How much, if any, of that data could be used towards the injectable IND is uncertain at this time.... IAG.....-kevtod |
| The
point is, we could have been doing ALL of these simultaneously. It's not
an either-or choice. And obviously minds (like those inhabiting ADVR management) that do not see the "and" in evaluating problems are severely limited to TWO choices - rather than a myriad of possibilities. Non-Aristotlean thinking trumps. |
| "So
who is to blame for the HPV setback?" The point is not "who's to blame," but rather WHY the new current management wants to continue working within the past paradigm of a flawed thinking process?? |
| "Are
you saying drug development is focused on the need to provide a product
that mitigates complications, cures diseases, offers relief. Or are you
saying revenues gained because of it were the original target?" There you go again with your "either/or" insinuations! How about BOTH?? |
| "Fast-Track"-
In the context of ADVR is nothing more than a term of HYPE.....It was
when the good Dr. H used it.....And it is still the same old song &
dance being used by Dr. Hawkins...... The best part is the people who continue to eat it up....Over & over again.....Just plain ridiculous to speak about "Fast-Track" for an IND that hasn't even been filed..... IAG.....-kevtod |
| I'm
willing to open a can of worms here and say I personally think one of
the BIG reasons we dropped Argentina results and testing - and went to
Weizmann/Israel has a LOT to do with SZH's personal comfortableness with
people of "his own kind" and friendships. And also his
aversion and discomfort with folks "south of the border" and
their way of consummating deals. One cannot forget SZH is a devout Orthodox Jew and Israel was the perfect place for him to meld his own personal/religious background with his scientific investigations. And be able to take trips there as business oriented ventures. Maybe I'm out of line here, but this IS my belief. Which points out one of SZH's negative traits - that of a willingness to enhance his own personal standing at the risk of harming the "team!"
|
||
| Study
Finds HIV Protein Can Drive Immune Cells Away 2004-05-05 Massachusetts General Hospital (MGH) researchers may have provided another clue to the mystery of how HIV, the virus that causes AIDS, evades the defenses of the immune system. In the May issue of the Journal of Virology, a team from the Partners AIDS Research Center at MGH describes finding how a key protein that helps the virus enter its target T helper cells may also keep away the T killer cells that should destroy HIV-infected cells. “One of the big questions in understanding HIV is why we can see immune responses that are effective in the test tube but do not eradicate the virus in the infected patient,” says Mark Poznansky, MD, PhD, of the Partners AIDS Research Center (PARC) and the MGH Infectious Disease Unit, the paper’s senior author. “We have identified a potential new mechanism by which pathogens can repel immune cells and thereby evade the immune system.” In 2000, Poznansky and colleagues published a report that found how a protein called SDF-1, known to attract immune cells, can actually repel T cells when present in elevated quantities. SDF-1 is a chemokine, a protein normally produced to summon immune cells to the site of an injury or infection. The molecule is known to interact with a T cell receptor called CXCR4 which also is used by HIV when it binds to and enters T helper cells. Investigating whether HIV infection involves the same kind of cellular repulsion observed in the earlier study – a process the researchers dubbed “fugetaxis” – seemed a logical next step. In a series of experiments led by Diana Brainard, MD, a research fellow in Poznansky’s lab, the team first found that while low concentration of gp120, the HIV protein that interacts with CXCR4, attracted T killer cells, higher concentrations induced the immune cells to move away. They then showed that it was the specific interaction of gp120 with CXCR4 that controlled T cell movement, and that the same repulsion could be produced specifically with T killer cells programmed to attack HIV. The researchers then used immunized mice to look at the effects of the viral protein in vivo. One day after the mice were injected with an antigen to which they had been previously immunized, they received an additional injection of either low- or high-dose recombinant gp120 protein or saline as a control. For up to 24 hours afterwards, mice receiving the high-dose gp120 were found to have a significantly lower immune response to the antigen injection than either control mice or those that had received the low-dose gp120. “This is the first report of fugetaxis caused by a viral gene product and could be an important way that HIV keeps the immune system at bay,” Poznansky says. “We don’t know yet if this process occurs in patients infected with HIV, but if it does, it provides a new therapeutic approach that could block this viral protein activity and allow immune cells to do their job.” Brainard and Poznansky add that this mechanism could also be used by other viruses – including the pox viruses, papilloma viruses and herpes viruses – that remain in the body after initial infection and have proteins known to influence cellular movement. Poznansky is an assistant professor of Medicine at Harvard Medical School. Additional co-authors are William Tharp, Elva Granado, Nicholas Miller, Alicja Trocha and Bruce Walker, MD, of MGH/PARC; Xiang-Hui Ren, MD, and Ernest Terwilliger, PhD, of Beth Israel Deaconess Medical Center; Brian Conrad, University of Michigan; and Richard Wyatt, Dana Farber Cancer Institute. The work was supported by grants from the U.S. Public Health Service and the American Foundation for AIDS Research. |
| Daily
Dosing of Growth Hormone Best for HIV Wasting Syndrome CME News Author: Laurie Barclay, MD CME Author: Charles Vega, MD, FAAFP Authors and Disclosures To earn CME credit, read the news brief, the paragraphs that follow, and answer the questions below. Release Date: April 22, 2004; Valid for credit through April 22, 2005 Credits Available Physicians - up to 0.25 AMA PRA category 1 credit(s) April 22, 2004 — Daily dosing of recombinant human growth hormone (rhGH) is superior to alternate dosing and to placebo for HIV-associated wasting syndrome, according to the results of a randomized, double-blind, placebo-controlled trial published in the April 1 issue of the Journal of Acquired Immune Deficiency Syndromes. "People with HIV still involuntarily lose both weight and lean body mass, despite the adoption of highly [active] antiretroviral therapy," Joseph M. Gertner, MD, vice president of medical affairs for Serono, Inc., says in a news release. "As demonstrated by these study results, [rhGH] is the only therapy shown clinically to build body mass and improve physical function in people with HIV-associated wasting." The double-blind phase of this trial was 12 weeks, followed by open-label extensions to 24 or 48 weeks. Of 757 HIV-infected subjects who were randomized to therapy with rhGH at 0.1 mg/kg up to a maximum of 6 mg daily or on alternate days, 555 subjects were evaluable for ergometry, 87.6% of whom were receiving highly active antiretroviral therapy (HAART). At 12 weeks, median maximum work output increased by 2.4 kJ in the alternate-day dosing group and by 2.6 kJ in the daily dosing group, with a median treatment difference of 2.9 kJ for daily dosing compared with placebo (P < .0001). Body weight increased by 2.2 kg in the alternate-day dosing group and by 2.9 kg in the daily dosing group, with corresponding median treatment differences of 1.5 kg and 2.2 kg vs. placebo (P < .0001). Bioelectric impedance spectroscopy revealed that fat mass (predominantly truncal) decreased, while lean body mass (LBM) increased by 3.3 kg in the alternate-day dosing group and by 5.2 kg in the daily dosing group (P < .0001 vs. placebo; P = .0173 vs. alternate-day dosing). Quality of life (QoL) improved significantly in both rhGH groups, without any significant changes in HIV viral load or in CD4 cell count. Adverse effects of fluid-retention and hyperglycemia were more common in the daily dosing than in the alternate-day dosing group. In both rhGH groups, patient perception of the effect of treatment on wasting symptoms was positive (P = .002 for the alternate-day dosing group and P = .0004 for the daily dosing group vs. placebo). Although bodily pain increased in a dose-dependent manner in both treatment groups, the pain did not interfere with normal work. Study limitations include possible enrollment of some patients with lipoatrophy, lack of a placebo control in the extension phase, and difficulty in determining how many patients might have had some degree of HIV-associated lipodystrophy. "Over the 12-week course of therapy, rhGH, 0.1 mg/kg daily dosing, was superior to placebo in improving physical function, body weight, body composition, and QoL and was superior to alternate-day dosing in restoring LBM," write Graeme J. Moyle, MD, PhD, from Chelsea and Westminster Hospital in London, U.K., and colleagues from the Serono 9037 Study Team. "However, alternate-day dosing was better tolerated, with fewer adverse events and less frequent hyperglycemia." Serono, Inc., funded this study, performed the data analysis and results reporting, and funded an external company to provide editorial services to the authors. J Acquir Immune Defic Syndr. 2004;35:367-375 Clinical Context Despite advances in HIV treatment, weight loss is still a significant problem for patients infected with HIV. Wasting is defined as an involuntary weight loss of 10% or more of normal body weight, and it is the first AIDS-defining illness in a significant minority of U.S. patients. Wasting can be secondary to poor nutrition, malabsorption, or increased resting energy loss. rhGH has been demonstrated to have a positive effect on wasting in HIV-infected patients. In a study by Schambelan in the Dec. 1, 1996, issue of the Annals of Internal Medicine, rhGH at a dose of 0.1 mg/kg/day was superior to placebo in improving weight gain, gains in LBM, and exercise tolerance. QoL scores were similar between the two groups. The Schambelan study did not include the number of patients receiving HAART, which is the standard of care now for patients with low CD4 cell counts, high viral loads, or who have progressed to AIDS. The authors of the current study sought to determine the efficacy and safety of rhGH in patients with HIV-related wasting syndrome who were also receiving HAART. Study Highlights Patients included in the study had documented HIV infection treated with HAART and were consuming at least 90% of their estimated caloric requirement. They had also experienced either at least a 10% body weight loss, had a body mass index (BMI) less than 20 kg/m2, or had a body weight less than 90% of the ideal. Exclusion criteria were fasting blood glucose greater than 6.7 mM or a history of carpal tunnel syndrome, coronary heart disease, or any disorder associated with at least moderate edema. Study participants were randomized to receive either rhGH at a dose of 0.1 mg/kg/day (maximum dose, 6 mg) or matching placebo. The rhGH group was further divided into daily dosing (DD) or alternate-day dosing (AD) groups. The placebo-controlled phase of the research lasted 12 weeks, at which time subjects were invited to participate in an open-label, 36-week extension of the trial. Study outcomes included maximal effort tests, as measured by cycle ergometry, and body weight and body composition determinations, measured by bioelectric impedance spectroscopy and whole-body dual-energy x-ray absorptiometry (DXA). QoL scores were also measured, as were adverse effects, measures of HIV activity, and metabolic studies. 757 subjects participated in this multicenter trial. 111 patients withdrew during the 12-week placebo-controlled trial. 177 participants completed 48 weeks of treatment, including the open-label phase of the study. Baseline characteristics were similar between the placebo, DD, and AD groups. 70.5% of all patients qualified for the study because of unintentional weight loss of more than 10%. 93% of all subjects were receiving HAART. Both the DD and AD groups had similar improvements in exercise tolerance compared with the placebo group. Exercise tolerance continued to improve in linear fashion during the open-label phase of the study. After 12 weeks, LBM increased by 3.3 kg from 48.4 kg in the AD group and by 5.2 kg from 49.3 kg in the DD group. Both treatment groups exhibited a statistically significant improvement in this outcome compared with placebo, and improvement in the DD group was superior to the AD group. Body cell mass increased in both treatment groups compared with placebo. Within the DD group, subjects in the lowest quartile of measured limb fat mass still experienced a greater increase in LBM compared with the placebo group, although subjects in the higher quartiles of limb fat mass had even greater increases in LBM with treatment. This finding was significant because it demonstrates that rhGH was effective in the presence of HIV-associated lipodystrophy. rhGH treatment continued to improve LBM gain during the open-label phase, with the DD group maintaining bigger increases than the AD group. Of patients whose BMI was less than 20 kg/m2, 45.5%, 25.8% and 10.8% recovered a BMI greater than 20 kg/m2 in the DD, AD, and placebo groups, respectively. QoL scores were improved over placebo to a similar degree in the DD and AD groups. Insulin-like growth factor I and insulin-like growth factor binding protein 3 were both elevated in a dose-dependent manner with rhGH treatment. DD patients experienced a higher mean increase in glucose levels compared with AD patients. 2 cases of hyperglycemia were reported during the study, and 1 patient developed new diabetes mellitus. Viral load and CD4 cell counts were not affected by rhGH treatment. The most common adverse events associated with rhGH therapy were arthralgia, myalgia, peripheral edema, hypoesthesia, and paresthesia. These adverse events were reported in 51.8% of the DD group, 49.8% of the AD group, and 28.7% of the placebo group. Only a minority of these adverse effects resolved with analgesia or dose adjustment. ********************************************************** IAG......-kevtod |