- Recent clinical trials have shown that HIV-1
replication can be dramatically curtailed, if not completely arrested,
with potent, rationally designed drug combinations.
- The benefits of combination therapy, however, are greatly
diminished in patients who have received previous anti-HIV therapy.
- Although 15 drugs have been approved by the United States
FDA (6 nucleoside analog RT inhibitors, 6 protease inhibitors, and 3 nonnucleoside
analog RT inhibitors), there is considerable cross-resistance within each
class of inhibitors.
- Several new anti-HIV drugs may be approved by the FDA
within the next few years, but preliminary data suggests that many of the
current drug-resistant HIV-1 isolates will also be resistant to these new
- Despite the availability of many anti-HIV drugs, it has
become increasingly difficult to effectively treat patients who fail an
initial combination therapy regimen or who are infected primarily with
drug resistant strains.
- Therefore, it is urgent to study whether patients developing
drug-resistant HIV-1 isolates during treatment with one anti-HIV regimen
can have a prolonged response to treatments with different anti-HIV drugs
or drug combinations.
- HIV-1 RT and protease sequences of clinical HIV-1 strains
reflect experiments of nature, which if collected and interpreted appropriately
can provide insight into HIV-1 drug resistance.
- However, only a small proportion of HIV-1 RT and protease
sequences are publicly available and there is no standard mechanism for
relating these sequences to other forms of data (e.g. drug treatment history,
in vitro drug susceptibility, and clinical outcome).
- A database linking HIV-1 RT and protease sequence data,
drug treatment histories, drug susceptibility, and clinical parameters
will allow researchers to assess the extent of clinical cross-resistance
among current and experimental anti-HIV drugs. At the same time, drug regimens
that do retain long-term effectiveness against particular drug-resistant
HIV-1 isolates may be identified.