[MoOrA1003] Dynamics of suppression of CXCR4 specific HIV-1 strains by antiviral therapy

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Dynamics of suppression of CXCR4 specific HIV-1 strains by antiviral therapy

[AUTHOR(S):] S. Philpott, H. Burger, C. Brunner, B. Weiser¹, K. Anastos, E. Salzer, E. Robison, H. Sacks, U. Mathur-Wagh², C. Ramirez Kitchen³, W.A. Meyer III⁴

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1003

BACKGROUND: Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 strains transmitted in vivo generally utilize CCR5 (R5 viruses), but later CXCR4 (X4) strains may emerge; this switch heralds CD4+ cell depletion and clinical deterioration. We examined the effect of combination antiviral therapy on HIV-1 coreceptor utilization and the dynamics of response. Previous studies of the dynamics of HIV-1 suppression by HAART have shown biphasic kinetics without focussing on coreceptor usage.

METHODS: We analyzed the coreceptor utilization of serial primary HIV-1 isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage of HIV-1 was determined in 105 primary isolates and 525 biological clones by using a HOS-CD4 cell system, and in 221 molecular clones of plasma HIV-1 by sequencing the V3 region of the env gene.

RESULTS: Mathematical analysis demonstrated a shift in the predominant viral population from X4 strains at baseline to the less cytopathic R5 strains after initiation of antiviral drugs (P<0.003). We have begun to characterize the dynamics of the shift in coreceptor utilization immediately following initiation of HAART. Data from two patients document a shift in the proportions of R5 and X4 utilizing strains within three days of starting HAART, with a complete suppression of X4 viruses obtained within two weeks of therapy. Other patients are under investigation to study the dynamics of the shift in coreceptor utilization.

CONCLUSIONS: Shifts in coreceptor usage may occur rapidly following the start of HAART and contribute to the clinical efficacy of anti-HIV drugs. The biphasic character of HIV-1 decline may reflect different kinetics related to the coreceptor utilization of the virus.

Presenting author: Sean Philpott

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1Wadsworth Center, New York State Dept. of Health, Wadsworth Center, New York State Dept. of Health, 120 New Scotland Avenue, Albany, NY 12208, United States

2Montefiore Medical Center-NYC WIHS, New York City, NY, United States.

3University of California at Los Angeles, Los Angeles, CA, United States.

4Quest Diagnostics, Inc, Baltimore, MD, United States.

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