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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.

Author information

1
Division of Infectious Diseases, Department of Medicine, Stanford University, California.
2
Department of Biology, Temple University, Philadelphia, Pennsylvania.
3
Division of Research, Kaiser Permanente Northern California, Oakland.
4
Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
5
Department of Infectious Diseases, Kaiser Permanente Northern California, Oakland.

Abstract

Background:

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

Methods:

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%.

Results:

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.

Conclusions:

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.

KEYWORDS:

HIV-1; network analysis; pol sequence; transmission

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