New Developments in the Biology and Treatment of HIV

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

New Developments in the Biology and Treatment of HIV

Proceedings of the National Academy of Science Online (09/15/98) Vol. 95, No. 19, P. 11041
Bushman, Frederic; Landau, Nathaniel R.; Emini, Emilio A.

The advent of protease inhibitors has dramatically increased treatment options for HIV-infected individuals. Combination therapy, generally involving two reverse transcriptase inhibitors and a protease inhibitor, has decreased the chance of drug-resistance development compared to earlier protease inhibitor monotherapy. Because HIV mutates at a very accelerated rate, resistance can occur easily. HIV strains must develop several mutations to become resistant to combination therapy, and mutations can only arise as a consequence of de novo mutation during replication in the presence of inhibitors. It appears that latent infections of HIV in certain cells occur even during combination therapy, but there is no evidence that the viruses mutate to confer drug-resistance during latent infection. However, new infections with drug-resistant HIV have been documented, and it is estimated that up to 40 percent of infected people in the United States may have protease inhibitor-resistant viruses. Furthermore, many patients cannot tolerate the adverse effects associated with protease inhibitor treatment. One treatment option being investigated are the protective effects of CCR5 mutations. Some researchers are also trying to create drugs that block the integrase enzyme that allows HIV to integrate into host DNA--a vital step in viral replication. Thus far, no proteins similar to integrase are known to be used by human cells, which may mean that integrase inhibitors will be fairly well tolerated. At present, however, many HIV-infected people live in developing nations and cannot afford any HIV treatment, so an HIV vaccine may be the only hope for treatment in many of these nations.

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