Several points about T-20....
I think that what was reported in the Nature journal was the preliminary data that was presented at the IDSA meeting in San Francisco in 1997.
natap.org
That link also includes a model or diagram of the supposed mechanism of action of the T-20 fusion inbibitor.
In the study reported in Nature Med, there were 16 patients, and the 4 in each group were each tested at different doses.
The four participants receiving the highest dose (100 mg) became undetectable, i.e. less than 500 copies, after 10-14 days of therapy.
The mean Baseline viral load was 4.2 log in this group and mean CD4 was 322.
The mean viral load decrease in this group was -1.5 log, and the mean CD4 increase was +52.
More recent details of the plans for further studies are available at: natap.org
It is thought likely that T-20 will be used only for salvage, as it must be administered parenterally, i.e. by subcutaneous injection or possibly with the use of the Minimed delivery system, a subcutaneous delivery system, like used by diabetics.
It is referred to as a proof-of-concept or proof-of-principle study, in that it shows that in a small group, the principle of inhibiting viral fusion can work, but it is still very early.
There are excellent articles at:
natap.org the site of NATAP, the National AIDS Treatment Advocacy Project, Executive Director-Jules Levin
A discussion of Novel Targets for antiretroviral agents was presented at Geneva by Dr. Dan Kuritzkes is at:
healthcg.com
"Interest in chemokines and their receptors has led to development of a number of agents capable of inhibiting HIV-1 entry by blocking the interaction of the external viral envelope protein gp120 with CCR5 or CXCR4. None of these agents has entered clinical trials to date. A theoretical concern with inhibitors of CCR5, which block entry of M-tropic or non-syncytium-inducing viruses, is that they will select for more virulent syncytium-inducing T-tropic viruses that make use of the alternative chemokine receptor CXCR4. Although agents that block binding of gp120 to CXCR4 have been described, these agents may have considerable toxicity, since CXCR4 appears to be an essential protein. Inhibition of HIV by this route is likely to be problematic. "
"Fusion inhibitors show greater promise. These agents work by binding to a critical domain of gp41, the transmembrane subunit of the HIV envelope glycoprotein. This so-called "fusion domain" is essential for fusion of the virus and cell membranes. Preliminary studies with one such inhibitor, T-20, show substantial antiviral activity in vivo that was accompanied by significant increases in CD4 count [5]. The major drawback of this compound is the need to deliver it parenterally. In addition, in vitro selection experiments demonstrate the ability to select for resistant variants that carry an alteration in the amino acid sequence of the fusion domain. Nevertheless, this important proof of principle suggests that further work on similar inhibitors may be fruitful."
As can be seen, there is no one method that will be perfect, which should be obvious.
A slightly different version of the T-20 news.
> HIV fusion inhibitor shows high potency
>
> WESTPORT, Nov 03 (Reuters Health) - The results of a phase I/IIB
> open-label trial of the investigational anti-HIV drug T-20, which has
> a mechanism of action distinct from reverse transcriptase and
> protease inhibitor drugs, indicate that it rapidly reduces viral load.
>
> In the November issue of Nature Medicine, Dr. Michael Saag, director
> of the AIDS Outpatient Clinic at the University of Alabama at
> Birmingham and colleagues report that after 14 days of treatment,
> T-20 appeared to be safe and provided "...potent inhibition of HIV
> replication comparable to anti-retroviral regimens approved at
> present."
>
> T-20 is a synthetic 36-amino acid peptide that "...blocks HIV-1
> gp41-mediated membrane fusion," they explain. Dr. Saag's group
> administered intravenous T-20 as monotherapy to 16 HIV-infected
> subjects who had a median CD4 baseline count of 212 cells per
> microliter and a median HIV RNA baseline load of 58,884 copies per
> milliliter. The subjects received one of the following doses of T-20:
> 3 mg, 10mg, 30mg or 100 mg twice daily.
>
> Overall, Dr. Saag's group observed "...no significant drug-related
> side effects, and the antiretroviral activity of the agent was
> unequivocal and of substantial magnitude." Dr. Saag told Reuters
> Health that, "...in the highest dose group, 4 of 4 patients developed
> undetectable levels of virus within 10 to 14 days after initiation of
> therapy and the median viral load pretherapy was about 30,000."
>
> These findings represent the "...first clinical demonstration, to our
> knowledge, that selective inhibition of HIV-1 fusion and entry in
> humans can lead to biologically significant reductions in plasma
> virus load," the group writes in the Nature Medicine paper.
>
> Dr. Saag told Reuters Health the findings provide
> "....proof-of-concept that an entirely new approach to antiretroviral
> therapy is viable." He predicted that T-20 would likely be used only
> as salvage therapy. "Because it is a peptide, it requires parenteral
> administration for it to be effective and there will, in all
> likelihood, be no oral formulation ever developed," he told Reuters
> Health.
>
> But Dr. Douglas D. Richman of the University of California San Diego,
> is not so sure. He wonders, in a commentary accompanying the study,
> "...if a complicated peptide shows this level of potency, could a
> smaller molecule with more desirable pharmacologic
> characteristics...be designed with similar activity?"
>
> Nature Med 1998;4:1232-1233,1302-1307.
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