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Duration of infection and low CD4:CD8 ratio correlate with CXCR4 utilization among HIV-1 subtype CRF01_AE
Presented by Utaiwan Utaipat, Thailand.
Utaipat U.1, Keitkarn J.1, Sakkhachornphop S.1, Tovanabutra S.2, Beyrer C.3, Khamboonrueng C.1, Sirisanthana T.1, Duerr A.4, Suriyanon V.1, Nelson K.E.3
1Research Institutes for Health Sciences, Chiang Mai University, Chiang Mai, Thailand, 2U.S. Military HIV Research Program (USMHRP), Henry M. Jackson Foundation, Rockville, MD, United States, 3Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States, 4Centers for Disease Control and Prevention, Atlanta, GA, United States
Objectives: To determine the prevalence of co-receptor usage and factors associated with CXCR4 utilization of HIV-1 isolated from participants in a heterosexual transmission cohort.
Methods: In 2000, 54 subjects, a subset of participants from the parent cohort of 624 Thai couples originally enrolled during 1992-1998 in Chiang Mai, Thailand were re-enrolled with consent into the present study in order to evaluate the virological and immunological parameters. The duration of seropositivity ranged from 4-12 years. HIV subtype was determined, viruses were isolated, and the major co-receptor utilization was assessed with the GHOST cells infection assay. Sequential lymphocyte (CD4, CD8, NK and B cells) counts, HIV-RNA levels, and duration of HIV-1 seropositivity were analyzed and the distribution was compared between subjects harboring R5 viruses and (R5X4 or X4) viruses. Uni- and multivariate logistic regression analyses were conducted to assess risk factors associated with CXCR4 usage.
Results: All subjects were HIV-1 CRF01_AE infected. Viruses were isolated from 50 individuals (92.6%): 58% harbored R5 virus, 42% had X4- or dual R5/X4-tropic viruses. Two (4%) participants were excluded because of prior drug treatment. While the characteristics at the baseline were indistinguishable between the R5- versus X4-group, the presence of X4 viruses was related to a longer duration of infection. Both groups had comparable plasma HIV RNA levels at the study visit. The X4 group had lower, but not-significantly different, CD4 counts. However, their CD8 counts were significantly higher than the R5 group. This reciprocal change was further revealed by a significantly lower CD4:CD8 ratio in the X4 group, regardless of the length of time that they had been infected
Conclusions: We found high prevalence of CXCR4 usage in this HIV-1 CRF01_AE- infected and ARV-untreated population. The usage of CXCR4 was independently associated with the duration of infection and the lower CD4:CD8 ratio.
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