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HIV-1 diversity, transmission dynamics and primary drug resistance in Angola.

Bártolo I, Zakovic S, Martin F, Palladino C, Carvalho P, Camacho R, Thamm S, Clemente S, Taveira N - PLoS ONE (2014)

Bottom Line: The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001).Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin.TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001).

View Article: PubMed Central - PubMed

Affiliation: Unidade dos Retrovírus e Infecções Associadas, Centro de Patogénese Molecular e Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal; Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal.

ABSTRACT

Objectives: To assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up.

Methods: Population sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug resistance mutations were identified using the Calibrated Population Resistance Tool (CPR). Transmission networks were determined using phylogenetic analysis of all Angolan sequences present in the databases. Evolutionary trends were determined by comparison with a similar survey performed in 2001.

Results: 47.1% of the viruses were pure subtypes (all except B), 47.1% were recombinants and 5.8% were untypable. The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001). The most frequent URFs comprised untypable sequences with subtypes H (U/H, n = 7, 10.8%), A (U/A, n = 6, 9.2%) and G (G/U, n = 4, 6.2%). Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission network analysis, 130 (35.7%) were part of a transmission network. Forty eight transmission clusters were identified; the majority (56.3%) comprised sequences sampled in 2008-2010 in Luanda which is consistent with a locally fuelled epidemic. Very low genetic distance was found in 27 transmission pairs sampled in the same year, suggesting recent transmission events.

Conclusions: Transmission of drug resistant strains was still negligible in Luanda in 2009, five years after the scale-up of ART. The dominance of small and recent transmission clusters and the emergence of new URFs are consistent with a rising HIV-1 epidemics mainly driven by heterosexual transmission.

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Transmission cluster analysis.Maximum likelihood tree with the 48 transmission clusters colored in green. Maximum likelihood tree was constructed in PhyML. Reliability of the tree was assessed using bootstrap resampling (1000 replicates). Bootstrap values and cluster number are indicated in each cluster. A bootstrap value of 0.7 (70%) or greater indicate significant support for the clusters. The scale represents number of base substitutions per site.
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pone-0113626-g003: Transmission cluster analysis.Maximum likelihood tree with the 48 transmission clusters colored in green. Maximum likelihood tree was constructed in PhyML. Reliability of the tree was assessed using bootstrap resampling (1000 replicates). Bootstrap values and cluster number are indicated in each cluster. A bootstrap value of 0.7 (70%) or greater indicate significant support for the clusters. The scale represents number of base substitutions per site.

Mentions: Forty eight transmission clusters were identified comprising 130 patient sequences (35.7% of the sampled patients) (Figure 3); more than half of these (52.3%) reported being heterosexual (Table S3). Consistent with this, small clusters comprising two closely related strains were dominant (n = 33, 68%). Only three large transmission chains, each comprising seven individuals, were found.


HIV-1 diversity, transmission dynamics and primary drug resistance in Angola.

Bártolo I, Zakovic S, Martin F, Palladino C, Carvalho P, Camacho R, Thamm S, Clemente S, Taveira N - PLoS ONE (2014)

Transmission cluster analysis.Maximum likelihood tree with the 48 transmission clusters colored in green. Maximum likelihood tree was constructed in PhyML. Reliability of the tree was assessed using bootstrap resampling (1000 replicates). Bootstrap values and cluster number are indicated in each cluster. A bootstrap value of 0.7 (70%) or greater indicate significant support for the clusters. The scale represents number of base substitutions per site.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257534&req=5

pone-0113626-g003: Transmission cluster analysis.Maximum likelihood tree with the 48 transmission clusters colored in green. Maximum likelihood tree was constructed in PhyML. Reliability of the tree was assessed using bootstrap resampling (1000 replicates). Bootstrap values and cluster number are indicated in each cluster. A bootstrap value of 0.7 (70%) or greater indicate significant support for the clusters. The scale represents number of base substitutions per site.
Mentions: Forty eight transmission clusters were identified comprising 130 patient sequences (35.7% of the sampled patients) (Figure 3); more than half of these (52.3%) reported being heterosexual (Table S3). Consistent with this, small clusters comprising two closely related strains were dominant (n = 33, 68%). Only three large transmission chains, each comprising seven individuals, were found.

Bottom Line: The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001).Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin.TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001).

View Article: PubMed Central - PubMed

Affiliation: Unidade dos Retrovírus e Infecções Associadas, Centro de Patogénese Molecular e Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal; Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal.

ABSTRACT

Objectives: To assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up.

Methods: Population sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug resistance mutations were identified using the Calibrated Population Resistance Tool (CPR). Transmission networks were determined using phylogenetic analysis of all Angolan sequences present in the databases. Evolutionary trends were determined by comparison with a similar survey performed in 2001.

Results: 47.1% of the viruses were pure subtypes (all except B), 47.1% were recombinants and 5.8% were untypable. The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001). The most frequent URFs comprised untypable sequences with subtypes H (U/H, n = 7, 10.8%), A (U/A, n = 6, 9.2%) and G (G/U, n = 4, 6.2%). Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission network analysis, 130 (35.7%) were part of a transmission network. Forty eight transmission clusters were identified; the majority (56.3%) comprised sequences sampled in 2008-2010 in Luanda which is consistent with a locally fuelled epidemic. Very low genetic distance was found in 27 transmission pairs sampled in the same year, suggesting recent transmission events.

Conclusions: Transmission of drug resistant strains was still negligible in Luanda in 2009, five years after the scale-up of ART. The dominance of small and recent transmission clusters and the emergence of new URFs are consistent with a rising HIV-1 epidemics mainly driven by heterosexual transmission.

Show MeSH
Related in: MedlinePlus