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Open Forum Infect Dis. 2019 Mar 14;6(4):ofz135. doi: 10.1093/ofid/ofz135. eCollection 2019 Apr.

National and International Dimensions of Human Immunodeficiency Virus-1 Sequence Clusters in a Northern California Clinical Cohort.

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Division of Infectious Diseases, Department of Medicine, Stanford University, California.
Department of Biology, Temple University, Philadelphia, Pennsylvania.
Division of Research, Kaiser Permanente Northern California, Oakland.
Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Department of Infectious Diseases, Kaiser Permanente Northern California, Oakland.



Recent advances in high-throughput molecular epidemiology are transforming the analysis of viral infections.


Human immunodeficiency virus (HIV)-1 pol sequences from a Northern Californian cohort (NCC) of 4553 antiretroviral-naive individuals sampled between 1998 and 2016 were analyzed together with 140 000 previously published global pol sequences. The HIV-TRAnsmission Cluster Engine (HIV-TRACE) was used to infer a transmission network comprising links between NCC and previously published sequences having a genetic distance ≤1.5%.


Twenty-five percent of NCC sequences were included in 264 clusters linked to a published sequence, and approximately one third of these (8.0% of the total) were linked to 1 or more non-US sequences. The largest cluster, containing 512 NCC sequences (11.2% of the total), comprised the subtype B lineage that traced its origin to the earliest North American sequences. Approximately 5 percent of NCC sequences belonged to a non-B subtype, and these were more likely to cluster with a non-US sequence. Twenty-two NCC sequences belonged to 1 of 4 large clusters containing sequences from rapidly growing regional epidemics: CRF07_BC (East Asia), subtype A6 (former Soviet Union), a Japanese subtype B lineage, and an East/Southeast Asian CRF01_AE lineage. Bayesian phylogenetics suggested that most non-B sequences resulted from separate introductions but that local spread within the largest CRF01_AE cluster occurred twice.


The NCC contains national and international links to previously published sequences including many to the subtype B strain that originated in North America and several to rapidly growing Asian epidemics. Despite their rapid regional growth, the Asian epidemic strains demonstrated limited NCC spread.


HIV-1; network analysis; pol sequence; transmission

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