Susan J Little1, Tom Chen2, Rui Wang2,3, Christy Anderson1, Sergei Kosakovsky Pond4, Masato Nakazawa1, William C Mathews5, Victor DeGruttola3, Davey M Smith1,6. 1. Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, California, USA. 2. Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Massachusetts, USA. 3. Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA. 4. Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, USA. 5. Department of Medicine, University of California San Diego, San Diego, California, USA. 6. San Diego Veterans Affairs Healthcare System, San Diego, California, USA.
Abstract
BACKGROUND: Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. METHODS: Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance-based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. RESULTS: Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09-113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. CONCLUSIONS: Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.
BACKGROUND: Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. METHODS: Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance-based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. RESULTS: Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09-113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. CONCLUSIONS: Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.
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