Impact of HIV-1 Subtypes on AIDS Progression in a Brazilian Cohort

Leite, Thaysse Cristina Neiva Ferreira; Campos, Dayse Pereira; Coelho, Alessandra Brum; Teixeira, Sylvia Lopes Maia; Veloso, Valdiléa G.; Morgado, Mariza G.; Guimarães, Monick Lindenmeyer

doi:10.1089/aid.2016.0126

Cited by 16 publications

(12 citation statements)

References 74 publications

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“…On the other hand, among migrants from Brazil, the epidemic is driven by subtype B (58%) followed by subtype C (12%), recombinants (10%) and subtype G (9%). _Consistently, previous studies in Brazil highlight that prevalence of subtype B is around 70-80% through the country followed by subtypes F1, C and recombinants BF1 [24][25][26][27]. Interestingly, we found 9% of Brazilian migrants infected with HIV-1 subtype G. Given the high prevalence of this subtype in Portugal [28] and its rarity in Brazil, this could indicate infections potentially acquired in Portugal, after migration.…”

Section: Discussionsupporting

confidence: 90%

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Pimentel

Pingarilho

Alves

et al. 2020

Viruses

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Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.

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Section: Discussionsupporting

confidence: 90%

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Pimentel

Pingarilho

Alves

et al. 2020

Viruses

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“…Median CD4 cell counts also differed significantly between cohorts, with subtype D-infected individuals exhibiting the lowest values (median, 110 [interquartile range {IQR}, 54 to 188] cells/mm 3 ) and subtype C-infected individuals exhibiting the highest values (median, 310 [IQR, 184 to 415] cells/mm 3 ) (overall P < 0.0001). While we do not know the time of infection for participants, these observations are consistent with prior studies demonstrating that HIV subtype D displays more rapid disease progression in regions where it cocirculates with subtype A or C strains ( 40 – 43 ).…”

Section: Resultssupporting

confidence: 90%

Differential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M Subtypes

Umviligihozo

Cobarrubias

Chandrarathna

et al. 2020

J Virol

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Downregulation of BST-2/tetherin and CD4 by HIV-1 viral protein U (Vpu) promotes viral egress and allows infected cells to evade host immunity. Little is known however about the natural variability in these Vpu functions among the genetically diverse viral subtypes that contribute to the HIV-1 pandemic. We collected Vpu isolates from 332 treatment-naive individuals living with chronic HIV-1 infection in Uganda, Rwanda, South Africa, and Canada. Together, these Vpu isolates represent four major HIV-1 group M subtypes (A [n = 63], B [n = 84], C [n = 94], and D [n = 59]) plus intersubtype recombinants and uncommon strains (n = 32). The ability of each Vpu clone to downregulate endogenous CD4 and tetherin was quantified using flow cytometry following transfection into an immortalized T-cell line and compared to that of a reference Vpu clone derived from HIV-1 subtype B NL4.3. Overall, the median CD4 downregulation function of natural Vpu isolates was similar to that of NL4.3 (1.01 [interquartile range {IQR}, 0.86 to 1.18]), while the median tetherin downregulation function was moderately lower than that of NL4.3 (0.90 [0.79 to 0.97]). Both Vpu functions varied significantly among HIV-1 subtypes (Kruskal-Wallis P < 0.0001). Specifically, subtype C clones exhibited the lowest CD4 and tetherin downregulation activities, while subtype D and B clones were most functional for both activities. We also identified Vpu polymorphisms associated with CD4 or tetherin downregulation function and validated six of these using site-directed mutagenesis. Our results highlight the marked extent to which Vpu function varies among global HIV-1 strains, raising the possibility that natural variation in this accessory protein may contribute to viral pathogenesis and/or spread. IMPORTANCE The HIV-1 accessory protein Vpu enhances viral spread by downregulating CD4 and BST-2/tetherin on the surface of infected cells. Natural variability in these Vpu functions may contribute to HIV-1 pathogenesis, but this has not been investigated among the diverse viral subtypes that contribute to the HIV-1 pandemic. In this study, we found that Vpu function differs significantly among HIV-1 subtypes A, B, C, and D. On average, subtype C clones displayed the lowest ability to downregulate both CD4 and tetherin, while subtype B and D clones were more functional. We also identified Vpu polymorphisms that associate with functional differences among HIV-1 isolates and subtypes. Our study suggests that genetic diversity in Vpu may play an important role in the differential pathogenesis and/or spread of HIV-1.

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“…Several viral factors are known to affect and modulate progression of HIV-1-related AIDS from the early assymptomatic phase of the disease, like the virus genetic diversity, viral fitness and co-receptor tropism [ 75 , 76 , 77 , 78 , 79 ]. In this context, we analyzed the archived HIV-1 proviral sequences from HIV patients in the early chronic phase of infection under HAART and with undetectable HIV viral load through NGS.…”

Section: Discussionmentioning

confidence: 99%

Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

Alves

Siqueira

Garrido³

et al. 2017

Viruses

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Increased access to highly active antiretroviral therapy (HAART) by human immunodeficiency virus postive (HIV+) individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

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Impact of HIV-1 Subtypes on AIDS Progression in a Brazilian Cohort

Cited by 16 publications

References 74 publications

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Differential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M Subtypes

Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

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