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HIV-1 transmission patterns in antiretroviral therapy-naïve, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing.

Ross LL, Horton J, Hasan S, Brown JR, Murphy D, DeJesus E, Potter M, LaMarca A, Melendez-Rivera I, Ward D, Uy J, Shaefer MS - PLoS ONE (2014)

Bottom Line: Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04).Both men-who-have-sex-with-men (MSM) (68% vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more frequent in VTCs than non-clustered sequences.Fewer VTCs subjects (as compared to those with non-clustering virus) had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study.

View Article: PubMed Central - PubMed

Affiliation: ViiV HealthCare, Research Triangle Park, North Carolina, United States of America.

ABSTRACT
Factors that contribute to the transmission of human immunodeficiency virus type 1 (HIV-1), especially drug-resistant HIV-1 variants remain a significant public health concern. In-depth phylogenetic analyses of viral sequences obtained in the screening phase from antiretroviral-naïve HIV-infected patients seeking enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto Rico (ClinicalTrials.gov NCT00440947) were examined for insights into the roles of drug resistance and epidemiological factors that could impact disease dissemination. Viral transmission clusters (VTCs) were initially predicted from a phylogenetic analysis of population level HIV-1 pol sequences obtained from 690 antiretroviral-naïve subjects in 2007. Subsequently, the predicted VTCs were tested for robustness by ultra deep sequencing (UDS) using pyrosequencing technology and further phylogenetic analyses. The demographic characteristics of clustered and non-clustered subjects were then compared. From 690 subjects, 69 were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04). VTCs had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p = 0.002) than non-clustered sequences. Both men-who-have-sex-with-men (MSM) (68% vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated antiretroviral therapy, 33 experienced confirmed virologic failure through 144 weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those with non-clustering virus) had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study. Our analysis shows specific geographical and drug resistance trends that correlate well with transmission clusters defined by HIV sequences of similarity. Furthermore, our study demonstrates the utility of molecular and epidemiological analysis of VTCs for identifying population-specific risks associated with HIV-1 transmission and developing effective local healthcare strategies.

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Related in: MedlinePlus

Prediction of VTCs by two studies using HIV-1 sequences obtained from pre-therapy subjects.Shown are comparisons of VTC numbers as predicted by NJ tree-reconstruction of either population-based, ultra-deep sequencing (UDS) or both datasets. See Methods and Materials for VTC prediction methodology.
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pone-0089611-g001: Prediction of VTCs by two studies using HIV-1 sequences obtained from pre-therapy subjects.Shown are comparisons of VTC numbers as predicted by NJ tree-reconstruction of either population-based, ultra-deep sequencing (UDS) or both datasets. See Methods and Materials for VTC prediction methodology.

Mentions: The majority of the predicted VTCs by either method overlapped; however there were 10 and 1 VTCs predicted by the population and UDS analyses, respectively, which were not identified by the other method. In total, 30 VTCs (composed of 69 subjects) were predicted by both methods and considered here as high confidence VTC predictions or VTCs (Figure 1). Composite NJ trees using both datasets are shown in Figure 2 and Figure S1.


HIV-1 transmission patterns in antiretroviral therapy-naïve, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing.

Ross LL, Horton J, Hasan S, Brown JR, Murphy D, DeJesus E, Potter M, LaMarca A, Melendez-Rivera I, Ward D, Uy J, Shaefer MS - PLoS ONE (2014)

Prediction of VTCs by two studies using HIV-1 sequences obtained from pre-therapy subjects.Shown are comparisons of VTC numbers as predicted by NJ tree-reconstruction of either population-based, ultra-deep sequencing (UDS) or both datasets. See Methods and Materials for VTC prediction methodology.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935917&req=5

pone-0089611-g001: Prediction of VTCs by two studies using HIV-1 sequences obtained from pre-therapy subjects.Shown are comparisons of VTC numbers as predicted by NJ tree-reconstruction of either population-based, ultra-deep sequencing (UDS) or both datasets. See Methods and Materials for VTC prediction methodology.
Mentions: The majority of the predicted VTCs by either method overlapped; however there were 10 and 1 VTCs predicted by the population and UDS analyses, respectively, which were not identified by the other method. In total, 30 VTCs (composed of 69 subjects) were predicted by both methods and considered here as high confidence VTC predictions or VTCs (Figure 1). Composite NJ trees using both datasets are shown in Figure 2 and Figure S1.

Bottom Line: Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04).Both men-who-have-sex-with-men (MSM) (68% vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more frequent in VTCs than non-clustered sequences.Fewer VTCs subjects (as compared to those with non-clustering virus) had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study.

View Article: PubMed Central - PubMed

Affiliation: ViiV HealthCare, Research Triangle Park, North Carolina, United States of America.

ABSTRACT
Factors that contribute to the transmission of human immunodeficiency virus type 1 (HIV-1), especially drug-resistant HIV-1 variants remain a significant public health concern. In-depth phylogenetic analyses of viral sequences obtained in the screening phase from antiretroviral-naïve HIV-infected patients seeking enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto Rico (ClinicalTrials.gov NCT00440947) were examined for insights into the roles of drug resistance and epidemiological factors that could impact disease dissemination. Viral transmission clusters (VTCs) were initially predicted from a phylogenetic analysis of population level HIV-1 pol sequences obtained from 690 antiretroviral-naïve subjects in 2007. Subsequently, the predicted VTCs were tested for robustness by ultra deep sequencing (UDS) using pyrosequencing technology and further phylogenetic analyses. The demographic characteristics of clustered and non-clustered subjects were then compared. From 690 subjects, 69 were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04). VTCs had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p = 0.002) than non-clustered sequences. Both men-who-have-sex-with-men (MSM) (68% vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated antiretroviral therapy, 33 experienced confirmed virologic failure through 144 weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those with non-clustering virus) had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study. Our analysis shows specific geographical and drug resistance trends that correlate well with transmission clusters defined by HIV sequences of similarity. Furthermore, our study demonstrates the utility of molecular and epidemiological analysis of VTCs for identifying population-specific risks associated with HIV-1 transmission and developing effective local healthcare strategies.

Show MeSH
Related in: MedlinePlus