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Viruses Utilizing Both CCR5 and CXCR4 Are Found in 5-13% of Acute HIV-1 Infections
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Reported by Jules Levin
3rd International Workshop on Targeting HIV Entry
Washington, DC, USA, December 7-8, 2007
P. Phung1, Y. Liu1, D. Han1, J. Reeves1, E. Coakley1, S. Little2, D. Richman2, C. Petropoulos1, N. Parkin1, T. Wrin1
1Monogram Biosciences, South San Francisco, CA.
2University of California, San Diego, CA.
Study Objectives:
Assess envelope coreceptor tropism of HIV-1 during acute and early infection
Two cohorts tested:
37 MSM acute/early infection longitudinal series
22 plasmapheresis donors
Tested for tropism:
TrofileTM
Enhanced Sensitivity TrofileTM - Seroconversion Panel
·3-10X more sensitive to detect minor variants in controlled expts
Author Summary and Conclusions:
--Viruses utilizing CCR5/CXCR4 (DM) represent 5% and 13% of isolates in the MSM and Seroconversion acute infection groups, respectively.
--In MSM group DM virus present at acute infection in 2 individuals and persisted for 2 and 3.5 years of followup
--Standard V3 genetic algorithms for prediction of CXCR4 usage worked best in the case of strong CXCR4 usage.
--Seroconversion panel shows that DM tropism may be found at the earliest viremic timepoint - the transmitted isolate is DM.
--Knowledge of coreceptor tropism in early infection may influence treatment decisions
--Must assume that some subjects in early infection harbor CXCR4 using isolates
Trofiile HIV Co--receptor Tropism Assay
Tropism determination based on infection of U87 cells expressing either CCR5 or CXCR4.
Use of coreceptor confirmed by inhibition with specific coreceptor inhibitor
Seroconversion Panel Isolates:
Plasmapheresis Donors
Seroconversiion Panel Viruses
--22 seronegative donors became infected during course of regular paid plasma donation
--Mode of transmission unknown
--Healthy throughout period of donation asymptomatic, afebrile
--Longitudinal plasmas collected every few days starting prior to first evidence of viremia through peak viral load and seroconversion
--Cloned viral env population from 68 total samples
--TrofileTM tropism and gp160 sequencing
--13.6% (3/22) of subjects infected with DM virus
1=Strong CXCR4 usage, 1=Low, 1=Weak
--Tropism constant throughout longitudinal samples
MSM Panel Isolates:
Longitudinal Samples Collected During
Acute/Early Infection
MSM Panel Viruses
--Acute Infection and Early Disease Research Program (AIEDRP) Study
--37 MSM acute/early longitudinals
--Entered study with acute infection syndrome
--Untreated through duration of study
--Followed for 4-61 months post-infection
--Frequent sample collection - tropism tested every 3-6 mo in first year and every 6 months after 1 year
--Median follow up: 16 months
--183 samples tested
--5.4% (2/37) of subjects infected with DM virus at acute infection
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