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CXCR4-Using HIV Found in 8.5% During Early HIV Infection
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Targeting HIV Entry: 3rd International Workshop
December 7-9, 2007
Washington, DC
Mark Mascolini
An enhanced coreceptor tropism assay from Monogram Biosciences spotted HIV that can use the CXCR4 (X4) receptor on CD4 cells in 5 of 59 people (8.5%) just diagnosed with HIV infection [1]. In all 5 people the X4-using virus persisted throughout follow-up, while X4 virus became detectable in several study participants during the early years of infection.
CCR5 (R5)-using virus establishes HIV infection in a large majority of people. But a growing body of work suggests X4 virus may be more common than previously realized during early infection.
The Monogram study involved 37 newly infected men who have sex with men (MSM) and 22 just-diagnosed paid blood donors. Physicians diagnosed HIV in the MSM when they sought care for symptoms of acute infection. The men gave plasma samples on their first visit and every 3 to 6 months afterwards for 4 to 61 months. Median follow-up measured 16 months. The 22 blood donors had no symptoms of acute infection when health workers spotted HIV in their samples. These people gave samples every few days for 1 to 4 weeks. None of the 59 study participants took antiretrovirals during the study period.
When diagnosed with HIV, 2 of the 37 MSM (5.4%) had dual/mixed (D/M)-tropic HIV--a viral population that can use either CXCR4 or CCR5. The D/M virus persisted in these 2 men throughout follow-ups of 13 and 21 months. Of the 35 people with R5-only virus during acute infection, D/M virus emerged in 6 men (16%) within 1 year of infection, and in 3 men in 18 months, 2 years, and 3 years after infection. Other studies detailed at this workshop and elsewhere correlate D/M virus with lower CD4 counts and higher viral loads [2-4].
D/M virus appeared in 3 of the 22 blood donors (13.6%) during acute HIV infection. This X4/R5-using virus persisted throughout the 1 to 4 weeks of blood collection.
The Monogram team saw no evidence that prevalence of X4 virus began fading in any of the MSM or blood donors studied. And emergence of X4-using HIV was not uncommon in MSM who had only R5 virus detectable at diagnosis.
"Given the strong association between CXCR4 tropism and clinical progression," Terri Wrin and colleagues noted, "knowledge of coreceptor usage at initial diagnosis may be important in deciding when to initiate therapy."
References
1. Wrin T, Phung P, Liu Y, et al. Viruses utilizing both CCR5 and CXCR4 are found in 5-13% of acute HIV-1 infections. Targeting HIV Entry: 3rd International Workshop. December 7-9, 2007. Washington, DC. Abstract 3.
2. Clax P, Rajicic N, Westby M, et al. Association between HIV-1 co-receptor tropism results and clinical and laboratory factors in 3862 patients screened for phase 3 clinical studies of maraviroc. Targeting HIV Entry: 3rd International Workshop. December 7-9, 2007. Washington, DC. Abstract 5.
3. Briz V, Poveda E, Martin-Carbonero L, et al. Impact of HAART on viral tropism evolution in HIV-infected patients followed for over 10 years. Targeting HIV Entry: 3rd International Workshop. December 7-9, 2007. Washington, DC. Abstract 4.
4. Wilkin TJ, Su Z, Kuritzkes DR, et al. HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis. 2007;44:591-595.
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