Joseph Sebastian

Phylogenetic insights into regional HIV transmission.

Objectives:Despite prevention efforts, new HIV diagnoses continue in the southern United States, where the epidemic is characterized by significant racial/ethnic disparities. We integrated phylogenetic analyses with clinical data to reveal trends in local HIV transmission. Design:Cross-sectional analysis of 1671 HIV-infected individuals each with one B-subtype pol sequence obtained during chronic (82%; UNC Center for AIDS Research Clinical Cohort) or acute/recent (18%; Duke/UNC Acute HIV Consortium) infection. Methods:Phylogenies were inferred using neighbor joining to select related sequences then confirmed with Bayesian methods. We characterized transmission clusters (clades n ≥ 3 sequences supported by posterior probabilities = 1) by factors including race/ethnicity and transmission risk. Factors associated with cluster membership were evaluated for newly diagnosed patients. Results:Overall, 72% were men, 59% black and 39% men who have sex with men (MSM). A total of 557 (33%) sequences grouped in either 108 pairs (n = 216) or 67 clusters (n = 341). Clusters ranged from three to 36 (median 4) members. Composition was delineated primarily by race, with 28% exclusively black, and to a lesser extent by risk group. Both MSM and heterosexuals formed discrete clusters, although substantial mixing was observed. In multivariable analysis, patients with age 30 years or less (P = 0.009), acute infection (P = 0.02), local residence (P = 0.002) and transmitted drug resistance (P = 0.02) were more likely to be cluster members, whereas Latinos were less likely (P < 0.001). Conclusion:Integration of molecular, clinical and demographic data offers a unique view into the structure of local transmission networks. Clustering by black race, youth and transmitted drug resistance and inability to identify Latino clusters will inform prevention, testing and linkage to care strategies.

HIV Transmission Patterns Among Immigrant Latinos Illuminated by the Integration of Phylogenetic and Migration Data.

Latinos represent a growing proportion of HIV cases in North Carolina (NC). Understanding how immigrants are involved in local HIV transmission is important to guide interventions. We used phylogenetics to characterize Latino involvement in local HIV transmission chains. Transmission clusters were identified from maximum-likelihood phylogenies constructed with HIV pol sequences from 177 Latinos and 1,496 non-Latinos receiving care in NC. Highly supported clusters involving one or more Latinos were characterized. Migration data were obtained from interviews and chart review. Factors associated with cluster membership were identified using log-binomial regression. Most Latinos were male (76%), immigrants (83%), and had HIV-1B (99%). Immigrants were more likely to report heterosexual risk (67% vs. 23%) than U.S.-born Latinos (p < 0.01). We identified 32 clusters that included one or more Latinos; these involved 53 Latinos (30%) and 41 non-Latinos. Immigrant and U.S.-born Latinos were equally likely to be in clusters, but immigrants were more likely to be in clusters with another Latino (78% vs. 29%; p = 0.02). Cluster composition by ethnicity and risk behavior varied by cluster size; larger clusters contained fewer immigrants and more men who have sex with men (MSM). Factors associated with immigrant membership in local transmission clusters included age <30 years [RR 2.34 (95% CI 1.47-3.73)], Mexican origin [RR 2.55 (95% CI 1.29-6.88)], and residing in the United States longer before diagnosis [RR 1.53 (95% CI 1.09-2.15), per 10 years]. While some Latinos immigrate with HIV infection, many immigrants are involved in transmission networks after arrival, particularly MSM. HIV testing and prevention interventions must consider this heterogeneity and may be better targeted by integrating phylogenetic analyses.

Rising prevalence of non-B HIV-1 subtypes in North Carolina and evidence for local onward transmission.

Abstract HIV-1 diversity is increasing in North American and European cohorts which may have public health implications. However, little is known about non-B subtype diversity in the southern United States, despite the region being the epicenter of the nation’s epidemic. We characterized HIV-1 diversity and transmission clusters to identify the extent to which non-B strains are transmitted locally. We conducted cross-sectional analyses of HIV-1 partial pol sequences collected from 1997 to 2014 from adults accessing routine clinical care in North Carolina (NC). Subtypes were evaluated using COMET and phylogenetic analysis. Putative transmission clusters were identified using maximum-likelihood trees. Clusters involving non-B strains were confirmed and their dates of origin were estimated using Bayesian phylogenetics. Data were combined with demographic information collected at the time of sample collection and country of origin for a subset of patients. Among 24,972 sequences from 15,246 persons, the non-B subtype prevalence increased from 0% to 3.46% over the study period. Of 325 persons with non-B subtypes, diversity was high with over 15 pure subtypes and recombinants; subtype C (28.9%) and CRF02_AG (24.0%) were most common. While identification of transmission clusters was lower for persons with non-B versus B subtypes, several local transmission clusters (≥3 persons) involving non-B subtypes were identified and all were presumably due to heterosexual transmission. Prevalence of non-B subtype diversity remains low in NC but a statistically significant rise was identified over time which likely reflects multiple importation. However, the combined phylogenetic clustering analysis reveals evidence for local onward transmission. Detection of these non-B clusters suggests heterosexual transmission and may guide diagnostic and prevention interventions.

Integration of contact tracing and phylogenetics in an investigation of acute HIV infection

Background The integration of traditional contact tracing with HIV sequence analyses offers opportunities to mitigate some of the barriers to effective network construction. We used combined analyses during an outbreak investigation of spatiotemporally clustered acute HIV infections to evaluate if the observed clustering was the product of a single outbreak. Methods We investigated acute and recent HIV index cases reported in North Carolina from 2013 to 2014 and their reported contacts. Contact tracing networks were constructed with surveillance data and compared with phylogenetic transmission clusters involving an index case using available HIV-1 pol sequences including 1672 references. Clusters were defined as clades of 2 or more sequences with a less than 1.5% genetic distance and a bootstrap of at least 98% on maximum-likelihood phylogenies. Results In total, 68 index cases and 210 contacts (71 HIV infected) were reported. The contact tracing network involved 58 components with low overall density (1.2% statewide); 33% of first-degree contacts could not be located. Among 38 (56%) of 68 index cases and 34 (48%) of 71 contacts with sequences, 13 phylogenetic clusters were identified (size 2–4 members). Four clusters connected network components that were not linked in contact tracing. The largest component (n = 28 cases) included 2 distinct phylogenetic clusters and spanned 2 regions. Conclusions We identified the concurrent expansion of multiple small transmission clusters rather than a single outbreak in a largely disconnected contact tracing network. Integration of phylogenetic analyses provided timely information on transmission networks during the investigation. Our findings highlight the potential of combined methods to better identify high-risk networks for intervention.