Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
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AIDS TREATMENT NEWS Issue #299, July 17, 1998
John S. James
- New antiretrovirals;
- Mechanisms of antiretroviral resistance;
- Relationship between phenotype, genotype, and clinical response;
- Combination therapy and its failure;
- Pathogenesis, dynamics, and transmission;
- Immune reconstitution; and
- Long-term suppression/eradication strategies.
We did not attend this highly technical meeting, which is limited mainly to those who are giving research presentations. But some of the major themes which emerged were summarized at the much larger Geneva conference by Dr. John W. Mellors. He noted several take-home messages:
* Second-generation protease inhibitors that are active against resistant HIV, in laboratory tests at least, are also active against wild-type virus, and are headed for phase III studies (large clinical trials).
* New resistance mutations have been reported--including a new kind of resistance mutation, a triple serine (S-S-S) around position 69 in the RT (reverse transcriptase) gene, caused by a doubling or insertion of codons in the gene, not by a substitution as is the case with the resistance mutations known so far. This S-S-S mutation, when combined with certain others, causes high-level resistance to AZT, d4T, and 3TC, and some increase in resistance to abacavir (1592), but it does not have much effect on ddI or ddC.
* In several retrospective studies in treatment-experienced patients, baseline phenotypic or genotypic resistance testing predicted response to new therapy--an important step toward validating the usefulness of these tests, although prospective studies are still needed.
* Viral rebound can occur even with wild-type virus (with no known resistance mutations). Apparently this means that drug failure often happens for reasons other than drug resistance.
* An important public-health concern is that drug-resistant HIV--including viruses which are resistant to many drugs--is being transmitted.
We will provide additional information on resistance in our ongoing coverage.
Meanwhile, you can hear Dr. Mellors' presentation on the Webcast or on audio tape (see "Geneva Conference: Finding Information on the Web and Elsewhere," in this issue).
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