AEGiS-15IAC: Evolution of HIV-1 coreceptor usage during antiretroviral therapy: a Bayesian approach.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Evolution of HIV-1 coreceptor usage during antiretroviral therapy: a Bayesian approach.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10145)

Kitchen CM, Philpott S, Burger H, Weiser B, Anastos K, Suchard MA
University of California, Los Angeles, Los Angeles, CA, United States

BACKGROUND: The rapid evolution of HIV-1 has complicated efforts to treat and prevent infection. There is substantial evidence for the on-going replication of HIV-1 in various compartments, even in individuals receiving highly active antiretroviral therapy (HAART). Viral evolution in the presence of antiviral therapy needs to be studied when developing new therapeutic strategies. Phylogenetic analyses can be used for this purpose, but may give rise to misleading results if rates of intra-patient evolution differ.

METHODS: The rapid evolution of HIV-1 has complicated efforts to treat and prevent infection. There is substantial evidence for the on-going replication of HIV-1 in various compartments, even in individuals receiving highly active antiretroviral therapy (HAART). Viral evolution in the presence of antiviral therapy needs to be studied when developing new therapeutic strategies. Phylogenetic analyses can be used for this purpose, but may give rise to misleading results if rates of intra-patient evolution differ.

RESULTS: The R5 virus that predominates after therapy may have evolved from various viral populations. Identifying the evolutionary origin of this virus is relevant to treatment strategies. Using our Bayesian model, we found that the R5 virus present after therapy was most closely related to predecessor R5 strains (Bayes Factor = 7.4; p ≤0.05). It is unlikely that this virus arose through continued evolution of X4 strains.

CONCLUSION: Understanding viral evolution under the selective pressure of antiretroviral therapy is an important step in understanding viral dynamics, drug resistance and the durability of clinical response to treatment. Our data suggest that therapies targeting R5 strains of HIV-1 may help further suppress viral replication and evolution of drug resistance. Finally, this Bayesian model is not limited to analyses of HIV-1 but can be used to elucidate evolutionary processes for other viruses as well.

Keywords: AEGIS, HIV-1, Antiretroviral Therapy, Highly Active, Virus Replication, HIV-1 Reverse Transcriptase, Evolution, Virus Diseases, Humans, therapy, virology, genetics, drug therapy

040711
A10145