[149] DYNAMICS OF SUPPRESSION OF CXCR4 SPECIFIC HIV-1 STRAINS BY ANTIVIRAL THERAPY

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] DYNAMICS OF SUPPRESSION OF CXCR4 SPECIFIC HIV-1 STRAINS BY ANTIVIRAL THERAPY

[AUTHOR(S):] S Philpott¹, H Burger^1,2, C Kitchen³, K Anastos⁴, E Salzer⁴, D Fish², N Dunn², E Robison⁴, C Brunner¹ and B Weiser^1,2
¹New York State Department of Health, Albany, NY; ²Albany Medical College, Albany, NY; ³University of California, Los Angeles, CA; and ⁴Montefiore Medical Center, Bronx, NY, USA

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 149
Antiviral Therapy 2003; 8(Suppl. 1):S220

[ABSTRACT:] HIV-1 coreceptor usage plays a crucial role in viral tropism, pathogenesis, and disease progression. HIV-1 strains that utilize CCR5 (R5) generally initiate infection; strains that use CXCR4 (X4) emerge later in ~50% of individuals and herald accelerated disease progression. We demonstrated previously that antiretroviral therapy can shift the predominant viral population from X4 strains at baseline to less cytopathic R5 strains after initiation of treatment. We developed a mathematical model to quantitate the proportion of HIV-1 in a clinical specimen utilizing each coreceptor. Early studies of the dynamics of HIV-1 suppression by HAART have shown biphasic kinetics, but the dynamics of the shift in coreceptor usage have not been examined. To characterize the dynamics of the shift in coreceptor utilization immediately following initiation of HAART, we focused on seven antiretroviralnaïve individuals who began treatment. In patients with X4 strains at the onset, a shift in the proportions of R5 and X4 viruses in the plasma occurred within 4 days of initiating HAART. Complete suppression of X4 viruses occurred within 2 weeks. There was a clear biphasic decline in HIV-1 RNA levels, with a precipitous decline in X4 virus followed by a slower diminution in R5 strains. A shift in HIV-1 coreceptor usage also occurred in viruses derived from the female genital tract, but the dynamics of decline differed somewhat from that observed in plasma. Shifts in HIV-1 coreceptor usage occur rapidly following initiation of HAART. The biphasic character of decline may reflect different kinetics related to coreceptor utilization by HIV-1.

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