Characterizing Hiv-1 Entry Phenotypes of Transmitted Viruses Across North Carolina

HIV-1 requires two components for cell entry: CD4 and a co-receptor (CCR5 or CXCR4). Wild-type transmitted HIV-1 typically uses CCR5 (R5-tropic), but discrete lineages with affinity for CXCR4 can emerge during untreated infection (X4/dual-tropic). Both are transmittable, but no standardized method exists for estimating the frequency of transmitted X4-tropic HIV, and its prevalence is not well characterized. Here, we use a combined genotyping and phenotyping approach to estimate frequency of X4 virus transmission in a large public health cohort. We estimate that 5.5% of all new transmissions were X4/dual-tropic and demonstrate that transmission clusters can be enriched with X4 viruses, suggesting potential circulation of X4 variants in the population. Transmitted X4 viruses were associated with significantly lower CD4+ T cell counts, and no transmitted M-tropic viruses were detected among phenotyped participants.