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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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Evolutionary relationships of the U/H recombinants.Sequences of U/H recombinants (named with 09AOHDP) were aligned with those of a previous study (named gb, GenBank)[4]._ENREF_4 The aLRT values supporting the internal branches defining a subtype or a sub-subtype are shown. The scale represents number of base substitutions per site.
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pone-0113626-g002: Evolutionary relationships of the U/H recombinants.Sequences of U/H recombinants (named with 09AOHDP) were aligned with those of a previous study (named gb, GenBank)[4]._ENREF_4 The aLRT values supporting the internal branches defining a subtype or a sub-subtype are shown. The scale represents number of base substitutions per site.

Mentions: Sequencing and phylogenetic analysis of the PR region was completed successfully for 139 (100%) patients; RT sequences were also obtained for all but one of these patients (n = 138, 99.3%). Phylogenetic analysis showed that all viruses belonged to HIV-1 group M (Figure 1 A and B). Out of the 138 isolates for which there was PR and RT sequences, 65 (47.1%) sequences were non-recombinant and 65 (47.1%) were recombinant, of which 11 (16.9%) were CRF02_AG, and 8 (5.8%) were untypable (U). The following pure subtypes and sub-subtypes were identified: A (n = 3, 4.6%), A1 (n = 1, 1.5%), A2 (n = 3, 4.6%), C (n = 24, 36.9%), D (n = 9, 13.8%), F1 (n = 13, 20.0%), G (n = 7, 10.8%), H (n = 3, 4.6%) and J (n = 2, 3.2%). Thirty different patterns of recombination were found. Subtypes A1, A2, A3, C, D, F1, G, H, J and K, and CRF02_AG and U sequences were involved in recombination events. Most of the recombinants (n = 54, 83.1%) were URFs; in almost half of the recombinants (n = 31, 47.7%) one of the regions was untypable. 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%). The U/H recombinants had a mean genetic distance of 0.062 substitutions per site and formed a highly supported monophyletic cluster in both genomic regions indicating that they share the same origin (Figure 1A and B). A similar U/H cluster has been described recently in Angola but the Province of origin of the patients in this cluster has not been disclosed [4]. Phylogenetic analyses revealed a close evolutionary relatedness of all U/H sequences suggesting that the origin of this emerging URF is Luanda (Figure 2).


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)

Evolutionary relationships of the U/H recombinants.Sequences of U/H recombinants (named with 09AOHDP) were aligned with those of a previous study (named gb, GenBank)[4]._ENREF_4 The aLRT values supporting the internal branches defining a subtype or a sub-subtype are shown. 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-g002: Evolutionary relationships of the U/H recombinants.Sequences of U/H recombinants (named with 09AOHDP) were aligned with those of a previous study (named gb, GenBank)[4]._ENREF_4 The aLRT values supporting the internal branches defining a subtype or a sub-subtype are shown. The scale represents number of base substitutions per site.
Mentions: Sequencing and phylogenetic analysis of the PR region was completed successfully for 139 (100%) patients; RT sequences were also obtained for all but one of these patients (n = 138, 99.3%). Phylogenetic analysis showed that all viruses belonged to HIV-1 group M (Figure 1 A and B). Out of the 138 isolates for which there was PR and RT sequences, 65 (47.1%) sequences were non-recombinant and 65 (47.1%) were recombinant, of which 11 (16.9%) were CRF02_AG, and 8 (5.8%) were untypable (U). The following pure subtypes and sub-subtypes were identified: A (n = 3, 4.6%), A1 (n = 1, 1.5%), A2 (n = 3, 4.6%), C (n = 24, 36.9%), D (n = 9, 13.8%), F1 (n = 13, 20.0%), G (n = 7, 10.8%), H (n = 3, 4.6%) and J (n = 2, 3.2%). Thirty different patterns of recombination were found. Subtypes A1, A2, A3, C, D, F1, G, H, J and K, and CRF02_AG and U sequences were involved in recombination events. Most of the recombinants (n = 54, 83.1%) were URFs; in almost half of the recombinants (n = 31, 47.7%) one of the regions was untypable. 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%). The U/H recombinants had a mean genetic distance of 0.062 substitutions per site and formed a highly supported monophyletic cluster in both genomic regions indicating that they share the same origin (Figure 1A and B). A similar U/H cluster has been described recently in Angola but the Province of origin of the patients in this cluster has not been disclosed [4]. Phylogenetic analyses revealed a close evolutionary relatedness of all U/H sequences suggesting that the origin of this emerging URF is Luanda (Figure 2).

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