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      High drug resistance levels could compromise the control of HIV infection in paediatric and adolescent population in Kinshasa, the Democratic Republic of Congo

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          Abstract

          Background

          The inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC).

          Methods

          From 2016–2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization.

          Results

          HIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants.

          Conclusion

          The high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.

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          RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies

          Alexandros Stamatakis (2014)
          Motivation: Phylogenies are increasingly used in all fields of medical and biological research. Moreover, because of the next-generation sequencing revolution, datasets used for conducting phylogenetic analyses grow at an unprecedented pace. RAxML (Randomized Axelerated Maximum Likelihood) is a popular program for phylogenetic analyses of large datasets under maximum likelihood. Since the last RAxML paper in 2006, it has been continuously maintained and extended to accommodate the increasingly growing input datasets and to serve the needs of the user community. Results: I present some of the most notable new features and extensions of RAxML, such as a substantial extension of substitution models and supported data types, the introduction of SSE3, AVX and AVX2 vector intrinsics, techniques for reducing the memory requirements of the code and a plethora of operations for conducting post-analyses on sets of trees. In addition, an up-to-date 50-page user manual covering all new RAxML options is available. Availability and implementation: The code is available under GNU GPL at https://github.com/stamatak/standard-RAxML. Contact: alexandros.stamatakis@h-its.org Supplementary information: Supplementary data are available at Bioinformatics online.
          Article 0 comments Cited 7198 times – based on 0 reviews     Review now
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            FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments

            Morgan N. Price, Paramvir S Dehal, Adam Arkin (2010)
            Background We recently described FastTree, a tool for inferring phylogenies for alignments with up to hundreds of thousands of sequences. Here, we describe improvements to FastTree that improve its accuracy without sacrificing scalability. Methodology/Principal Findings Where FastTree 1 used nearest-neighbor interchanges (NNIs) and the minimum-evolution criterion to improve the tree, FastTree 2 adds minimum-evolution subtree-pruning-regrafting (SPRs) and maximum-likelihood NNIs. FastTree 2 uses heuristics to restrict the search for better trees and estimates a rate of evolution for each site (the “CAT” approximation). Nevertheless, for both simulated and genuine alignments, FastTree 2 is slightly more accurate than a standard implementation of maximum-likelihood NNIs (PhyML 3 with default settings). Although FastTree 2 is not quite as accurate as methods that use maximum-likelihood SPRs, most of the splits that disagree are poorly supported, and for large alignments, FastTree 2 is 100–1,000 times faster. FastTree 2 inferred a topology and likelihood-based local support values for 237,882 distinct 16S ribosomal RNAs on a desktop computer in 22 hours and 5.8 gigabytes of memory. Conclusions/Significance FastTree 2 allows the inference of maximum-likelihood phylogenies for huge alignments. FastTree 2 is freely available at http://www.microbesonline.org/fasttree.
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              Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model.

              Reuben Granich, Charles F Gilks, Christopher Dye … (2009)
              Roughly 3 million people worldwide were receiving antiretroviral therapy (ART) at the end of 2007, but an estimated 6.7 million were still in need of treatment and a further 2.7 million became infected with HIV in 2007. Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease. We investigated a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination. We used mathematical models to explore the effect on the case reproduction number (stochastic model) and long-term dynamics of the HIV epidemic (deterministic transmission model) of testing all people in our test-case community (aged 15 years and older) for HIV every year and starting people on ART immediately after they are diagnosed HIV positive. We used data from South Africa as the test case for a generalised epidemic, and assumed that all HIV transmission was heterosexual. The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years. It could reduce HIV incidence and mortality to less than one case per 1000 people per year by 2016, or within 10 years of full implementation of the strategy, and reduce the prevalence of HIV to less than 1% within 50 years. We estimate that in 2032, the yearly cost of the present strategy and the theoretical strategy would both be US$1.7 billion; however, after this time, the cost of the present strategy would continue to increase whereas that of the theoretical strategy would decrease. Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics. This approach merits further mathematical modelling, research, and broad consultation.
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                Author and article information

                Contributors
                Marina Rubio-Garrido: Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Gabriel Reina:
                ORCID: https://orcid.org/0000-0003-4079-9753
                Role: Funding acquisitionRole: Project administrationRole: ValidationRole: Writing – review & editing
                Adolphe Ndarabu: Role: ConceptualizationRole: Data curationRole: Resources
                Ana Rodriguez-Galet: Role: Formal analysisRole: Investigation
                Ana Valadés-Alcaraz: Role: Formal analysisRole: Investigation
                David Barquín: Role: Data curation
                Silvia Carlos: Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – review & editing
                África Holguín: Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Jason T. Blackard: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 15 April 2021
                Publication date Collection: 2021
                Volume: 16
                Issue: 4
                Electronic Location Identifier: e0248835
                Affiliations
                [1 ] HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Ramón y Cajal-IRYCIS and CIBEREsp-RITIP-CoRISPe, Madrid, Spain
                [2 ] Microbiology Department, Clínica Universidad de Navarra, Navarra Institute for Health Research, Institute of Tropical Health, Universidad de Navarra, Pamplona, Spain
                [3 ] Monkole Hospital, Kinshasa, Democratic Republic of Congo
                [4 ] Department of Preventive Medicine and Public Health, Universidad de Navarra, Navarra Institute for Health Research, Institute of Tropical Health, Universidad de Navarra, Pamplona, Spain
                University of Cincinnati College of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-4079-9753
                Article
                Publisher ID: PONE-D-20-09317
                DOI: 10.1371/journal.pone.0248835
                PMC ID: 8049233
                PubMed ID: 33857166
                SO-VID: af5e22a9-5a43-49ee-ab31-790d5f825233
                Copyright © © 2021 Rubio-Garrido et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 1 April 2020
                Date accepted : 18 December 2020
                Page count
                Figures: 4, Tables: 1, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI16/01908
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI18/00904
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003425, Departamento de Educación, Gobierno de Navarra;
                Award ID: 045-2015
                Award Recipient :
                ORCID: https://orcid.org/0000-0003-4079-9753
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI16/01908
                Award Recipient :
                ORCID: https://orcid.org/0000-0003-4079-9753
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI18/00904
                Award Recipient :
                ORCID: https://orcid.org/0000-0003-4079-9753
                This study was funded by fundraising activities and donations (mainly from Bomberos Ayudan Association), and by Instituto de Salud Carlos III through the Projects PI16/01908 and PI18/00904" (Co-funded by European Regional Development Fund "A way to make Europe"/"Investing in your future") and the Government of Navarra (grant 045-2015).
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Medicine and Health Sciences
                Subject: Public and Occupational Health
                Subject: Preventive Medicine
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: People and Places
                Subject: Population Groupings
                Subject: Age Groups
                Subject: Children
                Subject: Adolescents
                Subject: People and Places
                Subject: Population Groupings
                Subject: Families
                Subject: Children
                Subject: Adolescents
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: HIV-1
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: HIV-1
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: HIV-1
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: HIV-1
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: HIV-1
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: HIV-1
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: HIV-1
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: HIV-1
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Medicine and Health Sciences
                Subject: Pediatrics
                Subject: Medicine and health sciences
                Subject: Medical conditions
                Subject: Infectious diseases
                Subject: Viral diseases
                Subject: HIV infections
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Protease Inhibitor Therapy
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Protease Inhibitor Therapy
                Subject: Medicine and Health Sciences
                Subject: Public and Occupational Health
                Subject: Preventive Medicine
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Protease Inhibitor Therapy
                Subject: Medicine and health sciences
                Subject: Epidemiology
                Subject: HIV epidemiology
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