Effects of mutations in the connection and RNase H domains of HIV-1 reverse transcriptase on drug susceptibility.

Ehteshami M, Götte M
AIDS Rev (2008), Volume 10, Page 224
PubMed entry

Abstract:

Despite the success in the development of antiretroviral therapy, the ...
Despite the success in the development of antiretroviral therapy, the emergence of drug resistance remains an important factor that can undermine the benefits of treatment. The vast majority of well-described resistance-associated mutations are clustered around the binding site for a given inhibitor. However, mutations that are observed at considerable distance from this location can likewise affect drug susceptibility. Treatment-associated mutations in the C-terminal region of HIV-1 reverse transcriptase provide a recently surfaced example in this regard. In this review, we discuss the potential clinical significance of these mutations and underlying molecular mechanisms. Routine resistance testing does not usually include the C-terminal region of HIV-1 reverse transcriptase. However, previous studies have shown that mutations in this region can reduce susceptibility to both nucleoside and nonnucleoside reverse transcriptase inhibitors. The prevalence of some of these mutations can be as high as reported for several classic resistance mutations in HIV-1 reverse transcriptase. Biochemical studies provided plausible mechanisms that help to explain how certain C-terminal mutations can contribute to alterations in drug susceptibility and viral replication capacity. Overall, the available data warrant further investigation on the impact of C-terminal mutations in combination with classic resistance-associated mutations, on changes in viral load, and response to treatment with different classes of reverse transcriptase inhibitors.

Polymerases:

Topics:

Health/Disease

Status:

new topics/pols set partial results complete validated

Results:

No results available for this paper.

Entry validated by:

Using Polbase tables:

Sorting:

Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).

Filtering:

It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.