Molecular Epidemiology of HIV-1 Subtype B Infection across Florida Reveals Few Large Superclusters with Metropolitan Origin

Florida is considered an epicenter of HIV in the United States. The U.S. federal plan for Ending the HIV Epidemic (EHE) within 10 years prioritizes seven of Florida's 67 counties for intervention. We applied molecular epidemiology methods to characterize the HIV infection networks in the state and infer whether the results support the EHE. HIV sequences (N = 34,446) and associated clinical/demographic metadata of diagnosed people with HIV (PWH), during 2007 to 2017, were retrieved from the Florida Department of Health. HIV genetic networks were investigated using MicrobeTrace. Associates of clustering were identified through boosted logistic regression. Assortative trait mixing was also assessed. Bayesian phylogeographic methods were applied to evaluate evidence of imported HIV-1 lineages and illustrate spatiotemporal flows within Florida. We identified nine large clusters spanning all seven EHE counties but little evidence of external introductions, suggesting-in the absence of undersampling-an epidemic that evolved independently from the rest of the country or other external influences. Clusters were highly assortative by geography. Most of the sampled infections (82%) did not cluster with others in the state using standard molecular surveillance methods despite satisfactory sequence sampling in the state. The odds of being unclustered were higher among PWH in rural regions, and depending on demographics. A significant number of unclustered sequences were observed in counties omitted from EHE. The large number of missing sequence links may impact timely detection of emerging transmission clusters and ultimately hinder the success of EHE in Florida. Molecular epidemiology may help better understand infection dynamics at the population level and underlying disparities in disease transmission among subpopulations; however, there is also a continuous need to conduct ethical discussions to avoid possible harm of advanced methodologies to vulnerable groups, especially in the context of HIV stigmatization. IMPORTANCE The large number of missing phylogenetic linkages in rural Florida counties and among women and Black persons with HIV may impact timely detection of ongoing and emerging transmission clusters and ultimately hinder the success of epidemic elimination goals in Florida.