Currently available anti-HIV therapy usually is able to suppress HIV activity, particularly in people with HIV/AIDS (PHAs) who are taking their first round of combination therapy. However, many PHAs will, at some point, develop treatment failure. As a result, new drugs are urgently needed.
One of the many new drugs under development is called T-20 (enfuvirtide). T-20 belongs to a new class of drugs called fusion inhibitors. Unlike currently licensed anti-HIV drugs, T-20 works by blocking HIV from entering a cell. Researchers in several continents have been testing T-20 in PHAs who have previously used combination therapy and the results are very promising. In this report, we will focus on the results from one study, called TORO 1, which was conducted in Canada, Brazil, Mexico and the U.S. The results from another study, TORO 2, were very similar.
All 491 subjects had prior exposure to all three classes of available anti-HIV drugs (nukes, non-nukes and protease inhibitors) or proof of viral resistance to these drugs. All subjects received what the researchers called "optimized background therapy" (OBT) — a combination of between three and five anti-HIV drugs that their doctors decided would be the best available option. Some subjects (326) were randomly assigned to also receive T-20, 90 mg twice daily, injected under the skin.
The profile of subjects at the start of the study was as follows:
The information released at the AIDS conference was gathered from the first six months of this study.
The proportion of subjects who had statistically significant decreases in viral load after six months was as follows:
Fewer than 400 copies –
Fewer than 50 copies –
The extra CD4+ cells seen in each study group were as follows:
Again, this difference between the two study groups was statistically significant; that is, not likely due to chance alone.
Two types of side effects were reported in this study:
As subjects in this study were generally not in the best state of health, side effects were common in both groups.
In the T-20 group, some of the side effects included:
Among the subjects who received OBT only, the proportion of those who reported these side effects was as follows:
Whether this difference was due to the use of T-20 is not clear.
Among subjects who received T-20, 98% developed redness and some swelling at the site where the drug was injected. In general, these injection site reactions (ISRs) were not severe, with up to 50% of subjects reporting no major pain or discomfort that limited their daily activity. In less than 10% of subjects receiving T-20, ISRs required the use of pain relief drugs.
Because T-20 needs to be injected twice daily, it is not for everyone. Moreover, in this study of heavily pre-treated subjects, not everyone who received T-20 showed sustained benefit. As well, resistance to T-20 can develop. When T-20 is taken in combination with previously unused drugs (for which there is no resistance), the antiviral response is likely to be greater than seen in either TORO 1 or TORO 2, but studies are needed to confirm this expectation. As T-20 is a difficult compound to make, it is not likely to be cheap. Based on their track record, regulatory authorities in Canada will not likely approve T-20 for at least a year after it is approved in the U.S.
REFERENCES
1. Henry K, Lalezari J, O'Hearn M, et al. Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals in North America and Brazil (TORO 1). XIV International AIDS Conference, July 7-12, 2002, Barcelona. LbOr 19B.
2. Kilby JM, Lalezari JP, Eron JJ, et al. "The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults.", AIDS Res Hum Retroviruses 2002 Jul 1;18(10):685-93.
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