In a letter to this week’s edition of the New England Journal of Medicine, Italian doctors have suggested that T-20 should be considered as a useful component of post-exposure prophylaxis. In particular, they recommend that the drug should be considered where the source of infection is a patient with resistance to multiple anti-HIV drugs.
The need for regimens which can combat protease inhibitor resistance is clear. The US Centers for Disease Control reported a case of infection with drug-resistant HIV despite post-exposure prophylaxis with a standard regimen in 2002.
In addition, nevirapine-containing PEP regimens have been associated with at least 22 cases of hepatotoxicity or severe rash in the United States, despite the view that nevirapine-containing regimens are better tolerated than indinavir-containing regimens.
NNRTI resistance is also becoming more common, and high levels of resistance have been identified in some locations such as San Diego and Vancouver, where early nevirapine and delavirdine studies were carried out.
However, the suitability of T-20 is uncertain. Although the authors note that T-20 reaches effective plasma levels sooner than other drugs due to its subcutaneous route of administration, it may be less well tolerated than other drugs such as tenofovir precisely because it is injectable.
As antiretroviral development places a greater premium on longer half-lives for drugs to be used in first-line therapy, more attention is likely to be paid to their employment in post-exposure prophylaxis – and pre-exposure prophylaxis.
The Gates Foundation is already funding a three year study of tenofovir as pre-exposure prophylaxis, using one tablet daily, in adults at high risk of sexual exposure in resource-limited settings.
At a recent London symposium on emerging therapies for HIV infection organised by NAM, Professor Brain Gazzard pointed out that any oral chemokine antagonist or entry inhibitor which had a half-life approaching 3-5 days (such as Schering Plough’s SCH-C) would be a highly attractive candidate for similar studies.
Further information on this website
Post-exposure prophylaxis - research overview
Prevention technologies - post-exposure prophylaxis
ARVS and HIV prevention 2003 - News story (December 2002).
Ferrant S et al. Enfuvirtide for prophylaxis against HIV infection. N Engl J Med 349 (8): 815, 2003.