Important note: Information in this article was accurate in March 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, March 15, 1999
Daniel J. DeNoon, Senior Editor
The drugs, HIV protease inhibitors, initiated the new era of highly active antiretroviral therapy (HAART) when it was found that in combination with nucleoside reverse transcriptase inhibitors they could reduce virus to undetectable levels. Despite their expense, the requirement that they be taken at the proper times each and every day, and their often difficult-to-manage side effects, this class of drugs remains a mainstay of AIDS therapy.
But now it seems that in a significant proportion of people, the virus has a head start on becoming functionally resistant to HIV protease inhibitors.
CDC researcher D. Pieniazek and colleagues analyzed protease gene sequences from 303 HIV isolates obtained from untreated patients in Africa, Asia, Europe, and the Americas.
"Of the 303 proteases, 285 (94 percent) contained at least one mutation in the gene at positions ... that have previously been shown to contribute to resistant to protease inhibitors," Pieniazek et al. reported.
Pieniazek announced the findings in a presentation to the 6th Conference on Retroviruses and Opportunistic Infections, held January 31-February 4, 1999, in Chicago, Illinois.
All of the virus isolates came from the main group of HIV and not from either of the two currently known outlying groups. They represented a cross section of HIV-1 clades: A (79 samples), B (95), B' (Thailand, 19), C (12), D (26), E (25), F (26), G (11), H (3), and seven unclassifiable viruses.
The B clade viruses had a different pattern of protease-inhibitor resistance than non-B clades, perhaps because the use of the drugs is mostly confined to areas where clade B is most prevalent.
"Our data indicate that viral variants with naturally protease- inhibitor-associated mutations exist in all analyzed HIV-1 subtypes regardless of the geographic origin," Pieniazek et al. concluded. "Our findings have important implications for investigation of novel protease inhibitors, their clinical evaluation, and implementation of protease inhibitors, especially in the developing world."
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