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Aggressive 3-DCR HIV Reported in New York

Recombinomics Commentary
February 13, 2005

>> A rare strain of H.I.V. that is highly resistant to virtually all anti-retroviral drugs and appears to lead to the rapid onset of AIDS was detected in a New York City man last week, city health officials announced on Friday.

It was the first time a strain of H.I.V. had been found that both showed resistance to multiple drugs and led to AIDS so quickly, the officials said. While the extent of the disease's spread is unknown, officials called a news conference to say that the situation is alarming. <<

The above case may raise the profile of problems associated with drug resistance in HIV.  There are 4 approved classes of anti-virals for AIDS that target 3 points in the life cycle of the retrovirus.  Two classes, nucleoside and non-nucleoside inhibitors of reverse transcriptase target the replication machinery of the virus.  A third class of drugs, protease inhibitors, targets the poly-protein processing by the virus.

Most approved drugs are in the three classes above, can be taken in pill form, and are used in various cocktails.

The fourth class targets viral entry into the cell.  It is a 36 aa synthetic peptide that binds to the first heptad repeat.  It requires injection and resistance can develop rapidly, especially when used as mono-therapy.  Thus, it seems likely that viruses with resistance to all four classes of drugs will develop.

It is unclear if the rapid progression in the individual in New York is due to added virulence by the virus, or increased susceptibility in the patient.  If the virus has resistance to the three major drug classes (3-DCR) and has increased virulence, the AIDS could rapidly become a significant health concern, and become more of an acute untreatable infection than a chronic manageable condition.

If AIDS becomes the former, more attention will focus on vaccine development.  HIV, like other infectious viral diseases evolves rapidly via recombination and is a target for novel approaches in vaccine development.

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