12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15–59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7–17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8–11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2–14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2–6.2) for protease inhibitors. Three (3.4% 95% CI 0.8–10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.

          Related collections

          Most cited references30

          • Record: found
          • Abstract: found
          • Article: not found

          HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study.

          There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance. We did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line ART, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. We did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. We identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. We assessed the risk factors of resistance with multilevel logistic regression with random coefficients. 2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62-204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6-6.7), ranging from 1.1% (two of 176; 0.0-2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5-17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9-14.2), compared with 3.5% (73 of 1866; 2.5-4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8-3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5-4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8-1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7-1.7) for dual-class resistance to NRTIs and NNRTIs. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the ART roll-out in a region was 1.38 (95% CI 1.13-1.68; p=0.001). The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of ART roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where ART programmes are scaled up. Ministry of Foreign Affairs of the Netherlands. Copyright © 2011 Elsevier Ltd. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment.

            The World Health Organization (WHO) HIV drug resistance (HIVDR) threshold survey method was developed for surveillance of transmitted HIVDR in resource-limited countries. The method is being implemented with minimal resources as a routine public health activity to produce comparable results in multiple countries and areas within countries. Transmitted drug resistant HIV strains will be seen first in cities or health districts where antiretroviral treatment (ART) has been widely available for years. WHO recommends countries begin surveillance in these areas. Each survey requires 15%. Use of routinely collected information and remnant specimens is recommended to minimize costs. Site and individual eligibility criteria are designed to minimize inclusion of ARV-experienced individuals and individuals infected before ART was available. Surveys have been implemented in 21 countries. In this supplement, seven countries report results of <5% transmitted HIVDR in areas where ART has been available for the longest time period. The main challenges in implementation are acquiring sufficient numbers of eligible specimens and optimizing specimen handling. The WHO HIVDR threshold survey method is feasible in resource-limited countries and produces information relevant to ART and drug resistance prevention planning.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Optimization of a Low Cost and Broadly Sensitive Genotyping Assay for HIV-1 Drug Resistance Surveillance and Monitoring in Resource-Limited Settings

              Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX. Conclusions The optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible for RLS where HIVDR surveillance is recommended to minimize the development and transmission of HIVDR.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 February 2017
                2017
                : 12
                : 2
                : e0171124
                Affiliations
                [1 ]Center for Global Health Research (CGHR), Kenya Medical Research Institute (KEMRI), Kisumu, Kenya
                [2 ]Epicentre, Médecins Sans Frontières (MSF), Paris, France
                [3 ]TransVIHMI IRD UMI 233 –INSERM U 1175 –Université de Montpellier, Montpellier, France
                [4 ]National AIDS and STI Control Programme (NASCOP), Ministry of Health, Nairobi, Kenya
                [5 ]US Centers for Disease Control and Prevention (CDC), Nairobi, Kenya
                [6 ]US Centers for Disease Control and Prevention (CDC), Kisumu, Kenya
                Universidad Autonoma de Madrid Centro de Biologia Molecular Severo Ochoa, SPAIN
                Author notes

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

                • Conceptualization: DM CZ.

                • Data curation: HO DM SI EA HF CZ.

                • Formal analysis: HO DM SI EA KW HF PO CZ.

                • Funding acquisition: DM.

                • Investigation: HO KW HF VO.

                • Methodology: DM CZ.

                • Project administration: DM CZ.

                • Resources: DM CZ.

                • Supervision: SI CZ.

                • Validation: HO KW HF VO.

                • Visualization: HO DM SI EA CZ.

                • Writing – original draft: HO SI EA.

                • Writing – review & editing: HO DM SI EA KW HF PO VO J-FE IM AAK CZ.

                ‡ These authors also contributed equally to this work.

                Article
                PONE-D-16-36615
                10.1371/journal.pone.0171124
                5298248
                28178281
                3d438821-d68e-46c7-93b2-1456af651b35

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 12 September 2016
                : 16 January 2017
                Page count
                Figures: 2, Tables: 3, Pages: 14
                Funding
                Funded by: Médecins Sans Frontières (MSF)
                Award Recipient :
                This work was funded by the Médecins Sans Frontières (MSF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                HIV-1
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                HIV-1
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                HIV-1
                Biology and Life Sciences
                Organisms
                Viruses
                Immunodeficiency Viruses
                HIV
                HIV-1
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Retroviruses
                Lentivirus
                HIV
                HIV-1
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Retroviruses
                Lentivirus
                HIV
                HIV-1
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Retroviruses
                Lentivirus
                HIV
                HIV-1
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Retroviruses
                Lentivirus
                HIV
                HIV-1
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
                Medicine and Health Sciences
                Pharmacology
                Antimicrobial Resistance
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                Biology and Life Sciences
                Organisms
                Viruses
                Immunodeficiency Viruses
                HIV
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Retroviruses
                Lentivirus
                HIV
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Retroviruses
                Lentivirus
                HIV
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Retroviruses
                Lentivirus
                HIV
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Retroviruses
                Lentivirus
                HIV
                People and Places
                Geographical Locations
                Africa
                Kenya
                People and Places
                Geographical Locations
                Africa
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Phylogenetic Analysis
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Phylogenetic Analysis
                Medicine and health sciences
                Diagnostic medicine
                HIV diagnosis and management
                Biology and Life Sciences
                Microbiology
                Virology
                Viral Transmission and Infection
                Viral Load
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. All 87 HIV-1 sequence files are available from the National Center for Biotechnology Information GenBank ( https://www.ncbi.nlm.nih.gov/genbank/) GenBank database (accession numbers KX790964-KX7910050).

                Uncategorized
                Uncategorized

                Comments

                Comment on this article