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1. Mortality from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing: a multicentre cohort study

Author

Kathrin Zürcher, MSc, Martina L Reichmuth, MSc, Marie Ballif, PhD, Chloé Loiseau, PhD, Sonia Borrell, PhD, Miriam Reinhard, Veronika Skrivankova, PhD, Rico Hömke, Peter Sander, MD, Anchalee Avihingsanon, MD, Alash'le G Abimiku, ProfPhD, Olivier Marcy, MD, Jimena Collantes, MSc, E Jane Carter, MD, Robert J Wilkinson, ProfPhD, Helen Cox, ProfPhD, Marcel Yotebieng, ProfMD, Robin Huebner, PhD, Lukas Fenner, ProfMD, Erik C Böttger, ProfMD, Sebastien Gagneux, ProfPhD, and Matthias Egger, ProfMD

Subjects
Medicine (General), R5-920, Microbiology, QR1-502
Abstract

Summary: Background: Drug resistance threatens global tuberculosis control. We aimed to examine mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and whole-genome sequencing (WGS). Methods: In this multicentre cohort study, we collected pulmonary Mycobacterium tuberculosis isolates and clinical data from individuals with tuberculosis from antiretroviral therapy programmes and tuberculosis clinics in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, Peru, South Africa, and Thailand, stratified by HIV status and drug resistance. Sites tested drug susceptibility using routinely available methods. WGS was done on Illumina HiSeq 2500 in the USA and Switzerland, and TBprofiler was used to analyse the genomes. We included individuals aged 16 years or older with pulmonary tuberculosis (bacteriologically confirmed or clinically diagnosed). We analysed mortality in multivariable logistic regression models adjusted for sex, age, HIV status, history of tuberculosis, and sputum positivity. Findings: Between Sept 1, 2014, and July 4, 2016, of 634 patients included in our previous analysis, we included 582 patients with tuberculosis (median age 33 years [IQR 27–43], 225 [39%] women, and 247 [42%] HIV-positive). Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-extensively drug-resistant (pre-XDR) or XDR. The analysis of mortality was based on 530 patients; 63 (12%) died and 77 (15%) patients received inappropriate treatment. Mortality ranged from 6% (18 of 310) in patients with pan-susceptible tuberculosis to 39% (nine of 23) in patients with pre-XDR or XDR tuberculosis. The adjusted odds ratio for mortality was 4·92 (95% CI 2·47–9·78) among undertreated patients, compared with appropriately treated patients. Interpretation: In seven countries with a high burden of tuberculosis, we observed discrepancies between drug resistance patterns obtained locally and WGS. The underdiagnosis of drug resistance resulted in inappropriate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information required to improve the outcomes of drug-resistant tuberculosis in high-burden settings. Our results support WHO's call for point-of-care tests based on WGS. Funding: National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, and Swiss National Center for Mycobacteria.

Published
2021
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2. Global and Regional Estimates for Subtype-Specific Therapeutic and Prophylactic HIV-1 Vaccines: A Modeling Study

Author

Ramyiadarsini Elangovan, Michael Jenks, Jason Yun, Leslie Dickson-Tetteh, Shona Kirtley, Joris Hemelaar, WHO-UNAIDS Network for HIV Isolation and Characterisation, Alash’le G Abimiku, Simon Agwale, Chris Archibald, Boaz Avidor, María Gabriela Barbás, Francoise Barre-Sinoussi, Banson Barugahare, El Hadj Belabbes, Silvia Bertagnolio, Deborah Birx, Aleksei F Bobkov, James Brandful, Helba Bredell, Catherine A Brennan, James Brooks, Marie Bruckova, Luigi Buonaguro, Franco Buonaguro, Stefano Buttò, Anne Buvé, Mary Campbell, Jean Carr, Alex Carrera, Manuel Gómez Carrillo, Connie Celum, Beth Chaplin, Macarthur Charles, Dimitrios Chatzidimitriou, Zhiwei Chen, Katsumi Chijiwa, David Cooper, Philip Cunningham, Anoumou Dagnra, Cillian F de Gascun, Julia Del Amo, Elena Delgado, Ursula Dietrich, Dominic Dwyer, Dennis Ellenberger, Barbara Ensoli, Max Essex, Hervé Fleury, Peter N Fonjungo, Vincent Foulongne, Deepak A Gadkari, Feng Gao, Federico García, Roger Garsia, Guy Michel Gershy-Damet, Judith R Glynn, Ruth Goodall, Zehava Grossman, Monick Lindenmeyer Guimarães, Beatrice Hahn, Raph L Hamers, Osamah Hamouda, Ray Handema, Xiang He, Joshua Herbeck, David D Ho, Africa Holguin, Mina Hosseinipour, Gillian Hunt, Masahiko Ito, Mohamed Ali Bel Hadj Kacem, Erin Kahle, Pontiano Kaleebu, Marcia Kalish, Adeeba Kamarulzaman, Chun Kang, Phyllis Kanki, Edward Karamov, Jean-Claude Karasi, Kayitesi Kayitenkore, Tony Kelleher, Dwip Kitayaporn, Leondios G Kostrikis, Claudia Kucherer, Claudia Lara, Thomas Leitner, Kirsi Liitsola, Jai Lingappa, Marek Linka, Ivette Lorenzana de Rivera, Vladimir Lukashov, Shlomo Maayan, Luzia Mayr, Francine McCutchan, Nicolas Meda, Elisabeth Menu, Fred Mhalu, Doreen Mloka, John L Mokili, Brigitte Montes, Orna Mor, Mariza Morgado, Fausta Mosha, Awatef Moussi, James Mullins, Rafael Najera, Mejda Nasr, Nicaise Ndembi, Joel R Neilson, Vivek R Nerurkar, Florian Neuhann, Claudine Nolte, Vlad Novitsky, Philippe Nyambi, Marianna Ofner, Fem J Paladin, Anna Papa, Jean Pape, Neil Parkin, Chris Parry, Martine Peeters, Alexandra Pelletier, Lucía Pérez-Álvarez, Deenan Pillay, Angie Pinto, Trinh Duy Quang, Cecilia Rademeyer, Filimone Raikanikoda, Mark A. Rayfield, Jean-Marc Reynes, Tobias Rinke de Wit, Kenneth E Robbins, Morgane Rolland, Christine Rousseau, Jesus Salazar-Gonzales, Hanan Salem, Mika Salminen, Horacio Salomon, Paul Sandstrom, Mario L Santiago, Abdoulaye D Sarr, Bryan Schroeder, Michel Segondy, Philippe Selhorst, Sylvester Sempala, Jean Servais, Ansari Shaik, Yiming Shao, Amine Slim, Marcelo A Soares, Elijah Songok, Debbie Stewart, Julie Stokes, Shambavi Subbarao, Ruengpung Sutthent, Jun Takehisa, Amilcar Tanuri, Kok Keng Tee, Kiran Thapa, Michael Thomson, Tyna Tran, Willy Urassa, Hiroshi Ushijima, Philippe van de Perre, Guido van der Groen, Kristel van Laethem, Joep van Oosterhout, Ard van Sighem, Eric van Wijngaerden, Anne-Mieke Vandamme, Jurgen Vercauteren, Nicole Vidal, Lesley Wallace, Carolyn Williamson, Dawit Wolday, Jianqing Xu, Chunfu Yang, Linqi Zhang, and Rong Zhang

Subjects
HIV, subtype, recombinant, CRF, URF, vaccine, Microbiology, QR1-502
Abstract

Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.

Published
2021
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3. Global associations of key populations with HIV-1 recombinants: a systematic review, global survey, and individual participant data meta-analysis

Author

Nkazi Nchinda, Ramyiadarsini Elangovan, Jason Yun, Leslie Dickson-Tetteh, Shona Kirtley, Joris Hemelaar, WHO-UNAIDS Network for HIV Isolation and Characterisation, Alash'le G. Abimiku, Simon Agwale, Chris Archibald, Boaz Avidor, Barbás María Gabriela, Francoise Barre-Sinoussi, Banson Barugahare, El Hadj Belabbes, Silvia Bertagnolio, Deborah Birx, Aleksei F. Bobkov, James Brandful, Helba Bredell, Catherine A. Brennan, James Brooks, Marie Bruckova, Luigi Buonaguro, Franco Buonaguro, Stefano Buttò, Anne Buve, Mary Campbell, Jean Carr, Alex Carrera, Manuel Gómez Carrillo, Connie Celum, Beth Chaplin, Macarthur Charles, Dimitrios Chatzidimitriou, Zhiwei Chen, Katsumi Chijiwa, David Cooper, Philip Cunningham, Anoumou Dagnra, Cillian F. de Gascun, Julia Del Amo, Elena Delgado, Ursula Dietrich, Dominic Dwyer, Dennis Ellenberger, Barbara Ensoli, Max Essex, Herve Fleury, Peter N. Fonjungo, Vincent Foulongne, Deepak A. Gadkari, Feng Gao, Federico García, Roger Garsia, Guy Michel Gershy-Damet, Judith R. Glynn, Ruth Goodall, Zehava Grossman, Monick Lindenmeyer Guimarães, Beatrice Hahn, Raph L. Hamers, Osamah Hamouda, Ray Handema, Xiang He, Joshua Herbeck, David D. Ho, Africa Holguin, Mina Hosseinipour, Gillian Hunt, Masahiko Ito, Mohamed Ali Bel Hadj Kacem, Erin Kahle, Pontiano Kaleebu, Marcia Kalish, Adeeba Kamarulzaman, Chun Kang, Phyllis Kanki, Edward Karamov, Jean-Claude Karasi, Kayitesi Kayitenkore, Tony Kelleher, Dwip Kitayaporn, Leondios G. Kostrikis, Claudia Kucherer, Claudia Lara, Thomas Leitner, Kirsi Liitsola, Jai Lingappa, Marek Linka, Ivette Lorenzana de Rivera, Vladimir Lukashov, Shlomo Maayan, Luzia Mayr, Francine McCutchan, Nicolas Meda, Elisabeth Menu, Fred Mhalu, Doreen Mloka, John L. Mokili, Brigitte Montes, Orna Mor, Mariza Morgado, Fausta Mosha, Awatef Moussi, James Mullins, Rafael Najera, Mejda Nasr, Nicaise Ndembi, Joel R. Neilson, Vivek R. Nerurkar, Florian Neuhann, Claudine Nolte, Vlad Novitsky, Philippe Nyambi, Marianna Ofner, Fem J. Paladin, Anna Papa, Jean Pape, Neil Parkin, Chris Parry, Martine Peeters, Alexandra Pelletier, Lucía Pérez-Álvarez, Deenan Pillay, Angie Pinto, Trinh Duy Quang, Cecilia Rademeyer, Filimone Raikanikoda, Mark A. Rayfield, Jean-Marc Reynes, Tobias Rinke de Wit, Kenneth E. Robbins, Morgane Rolland, Christine Rousseau, Jesus Salazar-Gonzales, Hanan Salem, Mika Salminen, Horacio Salomon, Paul Sandstrom, Mario L. Santiago, Abdoulaye D. Sarr, Bryan Schroeder, Michel Segondy, Philippe Selhorst, Sylvester Sempala, Jean Servais, Ansari Shaik, Yiming Shao, Amine Slim, Marcelo A. Soares, Elijah Songok, Debbie Stewart, Julie Stokes, Shambavi Subbarao, Ruengpung Sutthent, Jun Takehisa, Amilcar Tanuri, Kok Keng Tee, Kiran Thapa, Michael Thomson, Tyna Tran, Willy Urassa, Hiroshi Ushijima, Philippe van de Perre, Guido van der Groen, Kristel van Laethem, Joep van Oosterhout, Ard van Sighem, Eric van Wijngaerden, Anne-Mieke Vandamme, Jurgen Vercauteren, Nicole Vidal, Lesley Wallace, Carolyn Williamson, Dawit Wolday, Jianqing Xu, Chunfu Yang, Linqi Zhang, and Rong Zhang

Subjects
HIV, key populations, recombinant, CRF, URF, molecular epidemiology, Public aspects of medicine, RA1-1270
Abstract

IntroductionGlobal HIV infections due to HIV-1 recombinants are increasing and impede prevention and treatment efforts. Key populations suffer most new HIV infections, but their role in the spread of HIV-1 recombinants is unknown. We conducted a global analysis of the associations between key populations and HIV-1 recombinants.MethodsWe searched PubMed, EMBASE, CINAHL, and Global Health for HIV-1 subtyping studies published from 1/1/1990 to 31/12/2015. Unpublished data was collected through a global survey. We included studies with HIV-1 subtyping data of key populations collected during 1990-2015. Key populations assessed were heterosexual people (HET), men who have sex with men (MSM), people who inject drugs (PWID), vertical transmissions (VERT), commercial sex workers (CSW), and transfusion-associated infections (BLOOD). Logistic regression was used to determine associations of key populations with HIV-1 recombinants. Subgroup analyses were performed for circulating recombinant forms (CRFs), unique recombinant forms (URFs), regions, and time periods.ResultsEight hundred and eighty five datasets including 77,284 participants from 83 countries were included. Globally, PWID were associated with the greatest odds of recombinants and CRFs (OR 2.6 [95% CI 2.46–2.74] and 2.99 [2.83–3.16]), compared to HET. CSW were associated with increased odds of recombinants and URFs (1.59 [1.44–1.75] and 3.61 [3.15–4.13]). VERT and BLOOD were associated with decreased odds of recombinants (0.58 [0.54–0.63] and 0.43 [0.33–0.56]). MSM were associated with increased odds of recombinants in 2010–2015 (1.43 [1.35–1.51]). Subgroup analyses supported our main findings.DiscussionAs PWID, CSW, and MSM are associated with HIV-1 recombinants, increased preventative measures and HIV-1 molecular surveillance are crucial within these key populations.Systematic review registrationPROSPERO [CRD42017067164].

Published
2023
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4. Blueprint for building a biorepository in a resource-limited setting that follows international best practices

Author

Alash'le G. Abimiku, Talishea Croxton, Petronilla J. Ozumba, Ndidi Agala, Olasinbo Balogun, Emmanuel Jonathan, Enzenwa Onyemata, Kachimi Ndifon, Sunji Nadoma, Thankgod Anazodo, Sam Peters, and Christine M. Beiswanger

Subjects
biorepository, biobank, international guidelines, best practices, developing country, Public aspects of medicine, RA1-1270, Medicine (General), R5-920
Abstract

ackground:Genetic diversity is abundant on the African continent. However, genomic research has been hampered by a lack of high quality and extensively annotated biospecimens and the necessary infrastructure to support such a technology-intensive effort. Objective: The Institute of Human Virology Nigeria (IHVN) partnered with the H3Africa Consortium and the Coriell Institute for Medical Research to build an internationally recognised biorepository for the receipt, processing, storage and distribution of biospecimens for biomedical research. Here, the authors describe the procedures, challenges and results encountered. Results: Key requirements for a high-quality biorepository were identified: (1) institutional support of infrastructure and services, (2) on-site trained staff with primary commitment to the biorepository, (3) reliance on best practices from globally recognised biorepository groups, (4) early implementation of a quality management system, (5) adoption of a laboratory information management system with demonstrated versatility in functions, (6) collaboration with external experts and sharing of experience through abstracts, newsletters, published manuscripts, and attendance at meetings and workshops, (7) strict adherence to local and national ethical standards and (8) a sustainability plan that is reviewed and updated annually. Conclusion: Utilising published best practices of globally recognised experts in the biorepository field as a benchmark, IHVN expanded and reorganised its existing laboratory facility and staff to take on this new purpose.

Published
2019
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5. Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load

Author

Gambo G. Aliyu, Jonathan G. Lawton, Andrew B. Mitchell, Alash’le G. Abimiku, Tapdiyel Jelpe, Orji Bassey, David J. Riedel, Mahesh Swaminathan, Joy Chih-Wei Chang, Joshua R. DeVos, Hetal Patel, Man E. Charurat, and Kristen A. Stafford

Subjects
Adult, Anti-HIV Agents, Immunology, Nigeria, HIV Infections, Viral Load, Infectious Diseases, Cross-Sectional Studies, Drug Resistance, Viral, Mutation, Prevalence, HIV-1, Immunology and Allergy, Humans
Abstract

HIV drug resistance (HIVDR) surveillance is an important tool to monitor threats to progress towards epidemic control. The characterization of HIVDR in Nigeria at the national level is needed to inform both clinical decisions and population-level HIV policy strategies. This study uses data obtained from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) to describe the prevalence and distribution of HIVDR in Nigeria.NAIIS was a cross-sectional, population-based survey of households throughout Nigeria in 2018. NAIIS was designed to provide estimates of HIV prevalence and related health indicators from a nationally representative sample. The study population included participants aged 15-64 years who tested positive for HIV, had a viral load at least 1000 copies/ml, and had available HIV drug resistance genotypes. HIV isolates were genotyped to detect drug resistance mutations. Individual characteristics of study participants associated with HIVDR were identified using a weighted multivariable logistic regression model.Of 1355 respondents with available HIV genotypes, 293 (19%) had evidence of drug-resistant mutations (DRMs) that conferred resistance to at least one antiretroviral drug. The majority of DRMs observed conferred resistance to NNRTIs (17.6%) and NRTIs (11.2%). HIVDR was associated with being ART-experienced, longer duration on ART, and lower CD4+ count but not sociodemographic characteristics.The population level DRM prevalence in Nigeria was consistent with what would be expected in a mature HIV treatment landscape. The continued roll out of dolutegravir-anchored regimens should mitigate the impact of NNRTI resistance on population viral load suppression and progress towards epidemic control.

Published
2022

6. Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study

Author

Kathrin Zürcher, Marie Ballif, Lukas Fenner, Sonia Borrell, Peter M Keller, Joachim Gnokoro, Olivier Marcy, Marcel Yotebieng, Lameck Diero, E Jane Carter, Neesha Rockwood, Robert J Wilkinson, Helen Cox, Nicholas Ezati, Alash'le G Abimiku, Jimena Collantes, Anchalee Avihingsanon, Kamon Kawkitinarong, Miriam Reinhard, Rico Hömke, Robin Huebner, Sebastien Gagneux, Erik C Böttger, Matthias Egger, Frédérique Chammartin, Erik C. Boettger, Peter Keller, Alash'le Abimiku, Landry Wenzi, Martine Tabala, Robin Warren, Elizabeth Streicher, Robert J. Wilkinson, E. Jane Carter, Carlos Zamudio, Annette Sohn, Tor Petersen, Naruporn Kasipong, Kouassi N'Guessan, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Zurich, and Wellcome Trust

Subjects
Male, capreomycin, antibiotic resistance, 0302 clinical medicine, 1108 Medical Microbiology, amikacin, Peru, antibiotic agent, sputum cytodiagnosis, Aged, 80 and over, OUTCOMES, RESISTANT TUBERCULOSIS, 10179 Institute of Medical Microbiology, adult, cohort analysis, 3. Good health, priority journal, Cohort study, International epidemiology Databases to Evaluate AIDS (IeDEA) consortium, ieDEA, AFRICA, medicine.medical_specialty, Tuberculosis, 030106 microbiology, Immunology, Nigeria, Microbial Sensitivity Tests, HIV-INFECTED PATIENTS, purl.org/pe-repo/ocde/ford#3.03.08 [https], Sensitivity and Specificity, Microbiology, Article, Mycobacterium tuberculosis, 03 medical and health sciences, Drug Resistance, Bacterial, Humans, INTERNATIONAL EPIDEMIOLOGIC DATABASES, human, Diagnostic Errors, Ethambutol, Aged, RIFAMPIN, Science & Technology, bacterium isolate, medicine.disease, Survival Analysis, major clinical study, mortality, antibiotic sensitivity, Democratic Republic Congo, 570 Life sciences, biology, 0301 basic medicine, kanamycin, ethambutol, Drug resistance, rifampicin, Cohort Studies, South Africa, STARTING ANTIRETROVIRAL THERAPY, 030212 general & internal medicine, Human Biology & Physiology, EVALUATE AIDS IEDEA, Middle Aged, Thailand, Infectious Diseases, female, tuberculosis, Female, moxifloxacin, Life Sciences & Biomedicine, medicine.drug, Adult, Model organisms, isoniazid, pyrazinamide, Adolescent, streptomycin, Antibiotic sensitivity, 610 Medicine & health, Infectious Disease, PROFILE, IDLIC, Young Adult, male, Internal medicine, medicine, MANAGEMENT, controlled study, nonhuman, business.industry, FOS: Clinical medicine, 1103 Clinical Sciences, 2725 Infectious Diseases, Pyrazinamide, biology.organism_classification, bacterial strain, Kenya, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Rifampicin
Abstract

Summary Background Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory. Methods This multicentre cohort study was done in Cote d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status. Findings We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9–42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5–94·2) and specificity 84·3% (80·3–87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70–19·95) for patients with discordant results potentially leading to under-treatment. Interpretation Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis. Funding National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, Swiss National Center for Mycobacteria.

Published
2019
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7. HIV-1 recombinant poxvirus vaccine induces cross-protection against HIV-2 challenge in rhesus macaques

Author

Alash'le G. Abimiku, Genoveffa Franchini, James Tartaglia, Kristine Aldrich, Maria Myagkikh, Phillip D. Markham, Pele Chong, Michel Klein, Marie-Paule Kieny, Enzo Paoletti, Robert C. Gallo, and Marjorie Robert-Guroff

Subjects
Canarypox, Protein subunit, Molecular Sequence Data, HIV Core Protein p24, Immunization, Secondary, Human immunodeficiency virus (HIV), Enzyme-Linked Immunosorbent Assay, HIV Infections, Pilot Projects, Vaccinia virus, HIV Antibodies, HIV Envelope Protein gp120, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Avipoxvirus, HIV Envelope Protein gp160, law.invention, chemistry.chemical_compound, Immune system, Acquired immunodeficiency syndrome (AIDS), law, medicine, Animals, Amino Acid Sequence, Protein Precursors, AIDS Vaccines, Vaccines, Synthetic, Vaccination, Gene Products, env, General Medicine, biology.organism_classification, medicine.disease, Macaca mulatta, Virology, Peptide Fragments, chemistry, HIV-2, Immunology, HIV-1, Recombinant DNA, Vaccinia
Abstract

Rhesus macaques were immunized with attenuated vaccinia or canarypox human immunodeficiency virus type 1 (HIV-1) recombinants and boosted with HIV-1 protein subunits formulated in alum. Following challenge with HIV-2SBL6669, three out of eight immunized macaques resisted infection for six months and another exhibited significantly delayed infection, whereas all three naive controls became infected. Immunizations elicited both humoral and cellular immune responses; however, no clear correlates of protection were discerned. Although more extensive studies are now called for, this first demonstration of cross-protection between HIV-1 and -2 suggests that viral variability may not be an insurmountable problem in the design of a global AIDS vaccine.

Published
1995
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8. A Comprehensive Panel of Near-Full-Length Clones and Reference Sequences for Non-Subtype B Isolates of Human Immunodeficiency Virus Type 1

Author

Françoise Barré-Sinoussi, Feng Gao, Paul M. Sharp, Alagarsamy Srinivasan, David Robertson, George M. Shaw, Yalu Chen, Alash’le G. Abimiku, Sandra G. Morrison, Bixi Jian, Catherine D. Carruthers, Marc Girard, and Beatrice H. Hahn

Subjects
Adult, Male, Adolescent, ENVELOPE GENES, NEUTRALIZATION SEROTYPES, HIV TYPE-1, Immunology, Molecular Sequence Data, Viral Pathogenesis and Immunity, Biology, Microbiology, Genome, Genes, env, Virus, Frameshift mutation, Proviruses, Phylogenetics, Virology, Terminology as Topic, Humans, Amino Acid Sequence, GAG GENES, Cloning, Molecular, Gene, Phylogeny, Repetitive Sequences, Nucleic Acid, Genetics, Recombination, Genetic, MOLECULAR-CLONING, Phylogenetic tree, Middle Aged, Genes, gag, Long terminal repeat, Stop codon, Insect Science, THAILAND, HIV-1, GENETIC DIVERSITY, MOSAIC STRUCTURE, Female, AIDS VIRUSES, AFRICAN ORIGIN
Abstract

Non-subtype B viruses cause the vast majority of new human immunodeficiency virus type 1 (HIV-1) infections worldwide and are thus the major focus of international vaccine efforts. Although their geographic dissemination is carefully monitored, their immunogenic and biological properties remain largely unknown, in part because well-characterized virological reference reagents are lacking. In particular, full-length clones and sequences are rare, since subtype classification is frequently based on small PCR-derived viral fragments. There are only five proviral clones available for viruses other than subtype B, and these represent only 3 of the 10 proposed (group M) sequence subtypes. This lack of reference sequences also confounds the identification and analysis of mosaic (recombinant) genomes, which appear to be arising with increasing frequency in areas where multiple sequence subtypes cocirculate. To generate a more representative panel of non-subtype B reference reagents, we have cloned (by long PCR or lambda phage techniques) and sequenced 10 near-full-length HIV-1 genomes (lacking less than 80 bp of long terminal repeat sequences) from primary isolates collected at major epicenters of the global AIDS pandemic. Detailed phylogenetic analyses identified six that represented nonrecombinant members of HIV-1 subtypes A (92UG037.1), C (92BR025.8), D (84ZR085.1 and 94UG114.1), F (93BR020.1), and H (90CF056.1), the last two comprising the first full-length examples of these subtypes. Four others were found to be complex mosaics of subtypes A and C (92RW009.6), A and G (92NG083.2 and 92NG003.1), and B and F (93BR029.4), again emphasizing the impact of intersubtype recombination on global HIV-1 diversification. Although a number of clones had frameshift mutations or translational stop codons in major open reading frames, all the genomes contained a complete set of genes and three had intact genomic organizations without inactivating mutations. Reconstruction of one of these (94UG114.1) yielded replication-competent virus that grew to high titers in normal donor peripheral blood mononuclear cell cultures. This panel of non-subtype B reference genomes should prove valuable for structure-function studies of genetically diverse viral gene products, the generation of subtype-specific immunological reagents, and the production of DNA- and protein-based subunit vaccines directed against a broader spectrum of viruses.

Published
1998

9. Cross-protection of infant mice against intestinal colonisation by Campylobacter jejuni: importance of heat-labile serotyping (Lior) antigens

Author

Alash'le G. Abimiku and Jean M. Dolby

Subjects
Microbiology (medical), Serotype, Antigens, Bacterial, Hot Temperature, biology, Strain (chemistry), Spirillaceae, Heterologous, General Medicine, biology.organism_classification, Microbiology, Campylobacter jejuni, Virology, Intestines, Vaccination, Colonisation, Mice, Campylobacter fetus, Animals, Newborn, Antigen, Agglutination Tests, Bacterial Vaccines, Animals, Serotyping
Abstract

Summary Summary. An association of the heat-labile antigens detected by the Lior serotyping scheme with ability to protect infant mice against gastrointestinal colonisation with Campylobacter jejuni has been established. Overall, 39 (57%) of 68 infant mice challenged with a heterologous strain of the same Lior serotype as the vaccine strain were protected, compared with 40 (85%) of 47 infants protected against a homologous challenge. In contrast, none of the infant mice challenged with a strain carrying the same heat-stable antigens (i.e., of the same Penner serotype as the vaccine strain) were protected.

Published
1988
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10. Comparison of different vaccines and induced immune response againstCampylobacter jejunicolonization in the infant mouse

Author

Alash'le G. Abimiku, Jean M. Dolby, and S. P. Borriello

Subjects
Epidemiology, Administration, Oral, Enzyme-Linked Immunosorbent Assay, Campylobacter jejuni, Microbiology, Mice, Campylobacter fetus, Immune system, Pregnancy, Immunity, Campylobacter Infections, Animals, Mice, Inbred BALB C, biology, biology.organism_classification, Antibodies, Bacterial, Virology, Bacterial vaccine, Vaccination, Milk, Infectious Diseases, Vaccines, Inactivated, Bacterial Vaccines, Humoral immunity, biology.protein, Female, Antibody, Immunity, Maternally-Acquired, Injections, Intraperitoneal, Research Article
Abstract

SUMMARYThe degree of protection conferred by vaccinated dams on infant mice against colonization byCampylobacter jejunidepended on the bacterial strain, preparation, and route of administration of the vaccine. In some instances of homologous protection, serum bactericidal titres correlated well with protection. However, boiledC. jejunivaccine, which was non-protective, also elicited a strong bactericidal antibody response. Conversely, bactericidal activity could not be demonstrated against strains capable of cross-protection. There was a good correlation between high campylobacter-specific IgG response and bactericidal activity.

Published
1989
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11. The mechanism of protection of infant mice from intestinal colonisation with Campylobacter jejuni

Author

Jean M. Dolby and Alash'le G. Abimiku

Subjects
Microbiology (medical), Colon, Placenta, Microbiology, Campylobacter jejuni, Mice, Immune system, Campylobacter fetus, Immunity, Animals, IgA antibody, reproductive and urinary physiology, Mice, Inbred BALB C, biology, Colostrum, Vaccination, General Medicine, biology.organism_classification, Antibodies, Bacterial, Colonisation, Milk, Immunoglobulin G, Immunology, Bacterial Vaccines, biology.protein, Intestinal colonisation, Female, Antibody, Immunity, Maternally-Acquired
Abstract

Summary BALB/c mice, vaccinated intraperitoneally with a heat-killed (62°C) suspension of Campylobacter jejuni before mating, completely protect c. 90% of their own infants from intestinal colonisation. This protection has now been investigated further in fostering experiments. Fostering by vaccinated dams within the first 24 h of life prevented intestinal colonisation in 50% of infants from non-vaccinated dams, and reduced colonisation in a further 25%. Infants from vaccinated dams, even if allowed to receive their own mothers’ colostrum and milk, became susceptible to challenge when subsequently fostered by non-vaccinated dams. Immunity in experimentally infected infant mice depended upon the consumption of immune milk at and after the time of challenge. High concentrations of IgG antibodies specific for C. jejuni were found in the serum and mammary secretion of vaccinated dams, but there was very little specific IgA antibody.

Published
1987

12. Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis

Author

Hemelaar, Joris, Elangovan, Ramyiadarsini, Yun, Jason, Dickson-Tetteh, Leslie, Fleminger, Isabella, Kirtley, Shona, Williams, Brian, Gouws-Williams, Eleanor, Ghys, Peter D, Abimiku, Alash'le G, Agwale, Simon, Archibald, Chris, Avidor, Boaz, Barbás, María Gabriela, Barre-Sinoussi, Francoise, Barugahare, Banson, Belabbes, El Hadj, Bertagnolio, Silvia, Birx, Deborah, Bobkov, Aleksei F, Brandful, James, Bredell, Helba, Brennan, Catherine A, Brooks, James, Bruckova, Marie, Buonaguro, Luigi, Buonaguro, Franco, Buttò, Stefano, Buve, Anne, Campbell, Mary, Carr, Jean, Carrera, Alex, Carrillo, Manuel Gómez, Celum, Connie, Chaplin, Beth, Charles, Macarthur, Chatzidimitriou, Dimitrios, Chen, Zhiwei, Chijiwa, Katsumi, Cooper, David, Cunningham, Philip, Dagnra, Anoumou, de Gascun, Cillian F, Del Amo, Julia, Delgado, Elena, Dietrich, Ursula, Dwyer, Dominic, Ellenberger, Dennis, Ensoli, Barbara, Essex, Max, Gao, Feng, Fleury, Herve, Fonjungo, Peter N, Foulongne, Vincent, Gadkari, Deepak A, García, Federico, Garsia, Roger, Gershy-Damet, Guy Michel, Glynn, Judith R, Goodall, Ruth, Grossman, Zehava, Lindenmeyer-Guimarães, Monick, Hahn, Beatrice, Hamers, Raph L, Hamouda, Osamah, Handema, Ray, He, Xiang, Herbeck, Joshua, Ho, David D, Holguin, Africa, Hosseinipour, Mina, Hunt, Gillian, Ito, Masahiko, Bel Hadj Kacem, Mohamed Ali, Kahle, Erin, Kaleebu, Pontiano Kaleebu, Kalish, Marcia, Kamarulzaman, Adeeba, Kang, Chun, Kanki, Phyllis, Karamov, Edward, Karasi, Jean-Claude, Kayitenkore, Kayitesi, Kelleher, Tony, Kitayaporn, Dwip, Kostrikis, Leondios G, Kucherer, Claudia, Lara, Claudia, Leitner, Thomas, Liitsola, Kirsi, Lingappa, Jai, Linka, Marek, Lorenzana de Rivera, Ivette, Lukashov, Vladimir, Maayan, Shlomo, Mayr, Luzia, McCutchan, Francine, Meda, Nicolas, Menu, Elisabeth, Mhalu, Fred, Mloka, Doreen, Mokili, John L, Montes, Brigitte, Mor, Orna, Morgado, Mariza, Mosha, Fausta, Moussi, Awatef, Mullins, James, Najera, Rafael, Nasr, Mejda, Ndembi, Nicaise, Neilson, Joel R, Nerurkar, Vivek R, Neuhann, Florian, Nolte, Claudine, Novitsky, Vlad, Nyambi, Philippe, Ofner, Marianna, Paladin, Fem J, Papa, Anna, Pape, Jean, Parkin, Neil, Parry, Chris, Peeters, Martine, Pelletier, Alexandra, Pérez-Álvarez, Lucía, Pillay, Deenan, Pinto, Angie, Quang, Trinh Duy, Rademeyer, Cecilia, Raikanikoda, Filimone, Rayfield, Mark A, Reynes, Jean-Marc, Rinke de Wit, Tobias, Robbins, Kenneth E, Rolland, Morgane, Rousseau, Christine, Salazar-Gonzales, Jesus, Salem, Hanan, Salminen, Mika, Salomon, Horacio, Sandstrom, Paul, Santiago, Mario L, Sarr, Abdoulaye D, Schroeder, Bryan, Segondy, Michel, Selhorst, Philippe, Sempala, Sylvester, Servais, Jean, Shaik, Ansari, Shao, Yiming, Slim, Amine, Soares, Marcelo A, Songok, Elijah, Stewart, Debbie, Stokes, Julie, Subbarao, Shambavi, Sutthent, Ruengpung, Takehisa, Jun, Tanuri, Amilcar, Tee, Kok Keng, Thapa, Kiran, Thomson, Michael, Tran, Tyna, Urassa, Willy, Ushijima, Hiroshi, van de Perre, Philippe, van der Groen, Guido, van Laethem, Kristel, van Oosterhout, Joep, van Sighem, Ard, van Wijngaerden, Eric, Vandamme, Anne-Mieke, Vercauteren, Jurgen, Vidal, Nicole, Wallace, Lesley, Williamson, Carolyn, Wolday, Dawit, Xu, Jianqing, Yang, Chunfu, Zhang, Linqi, Zhang, Rong, John Radcliffe Hospital [Oxford University Hospital], Centre for Statistics in Medicine, University of Oxford [Oxford], Stellenbosch University, UNAIDS [Genève, Suisse] (ONUSIDA), Institut Pasteur [Paris], Noguchi Memorial Institute for Medical Research [Accra, Ghana] (NMIMR), University of Ghana, Institute of Tropical Medicine [Antwerp] (ITM), State Key Laboratory of Silkworm Genome Biology, Southwest University, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Georg-Speyer-Haus, The University of Sydney, National AIDS Centre, Istituto Superiore di Sanita [Rome], Harvard School of Public Health, Digital Enterprise Research Institute (DERI-NUIG), National University of Ireland [Galway] (NUI Galway), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Departments of Medicine and Microbiology, University of Alabama at Birmingham [ Birmingham] (UAB), Robert Koch Institute [Berlin] (RKI), Beihang University (BUAA), Statens Serum Institut [Copenhagen], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), SANTE/SIDA [Bobo-Dioulasso, Burkina Faso], Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Department of Microbiology, University of Washington School of Medicine, Department of Microbiology, Medical School, University of Thessaly [Volos] (UTH), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Africa Centre for Health and Population Studies, University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Lab-STICC_UBO_CID_IHSEV, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), State Key Laboratory of Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Laboratory of Virology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Universidade Federal do Rio de Janeiro (UFRJ), Departements of Medicine and Microbiology, University of Alabama [Tuscaloosa] (UA), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Département Génétique Internal Médecine, Hôpital Universitaire Leuven, Department of Chemical and Biomolecular Engineering [Baltimore], Johns Hopkins University (JHU), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, China Academy of Chinese Medical Sciences, Chatzidimitriou, Dimitrios [0000-0001-9656-5898], University of Oxford, Institut Pasteur [Paris] (IP), Istituto Superiore di Sanità (ISS), Microbiologie Fondamentale et Pathogénicité (MFP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), UNAIDS, Noguchi Memorial Institute for Medical Research, University of Ghana, Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Beihang University, Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Nuffield Department of Women's and Reproductive Health (NDWRH), University of Oxford- John Radcliffe Hospital [Oxford University Hospital], South African Centre for Epidemiological Modelling and Analysis, JH is supported by the Oxford University Clinical Academic Graduate School (Oxford, UK) and Linacre College, Oxford University (Oxford, UK)., WHO–UNAIDS Network for HIV Isolation Characterisation : Alash'le G Abimiku, Simon Agwale, Chris Archibald, Boaz Avidor, María Gabriela Barbás, Francoise Barre-Sinoussi, Banson Barugahare, El Hadj Belabbes, Silvia Bertagnolio, Deborah Birx, Aleksei F Bobkov, James Brandful, Helba Bredell, Catherine A Brennan, James Brooks, Marie Bruckova, Luigi Buonaguro, Franco Buonaguro, Stefano Buttò, Anne Buve, Mary Campbell, Jean Carr, Alex Carrera, Manuel Gómez Carrillo, Connie Celum, Beth Chaplin, Macarthur Charles, Dimitrios Chatzidimitriou, Zhiwei Chen, Katsumi Chijiwa, David Cooper, Philip Cunningham, Anoumou Dagnra, Cillian F de Gascun, Julia Del Amo, Elena Delgado, Ursula Dietrich, Dominic Dwyer, Dennis Ellenberger, Barbara Ensoli, Max Essex, Feng Gao, Herve Fleury, Peter N Fonjungo, Vincent Foulongne, Deepak A Gadkari, Federico García, Roger Garsia, Guy Michel Gershy-Damet, Judith R Glynn, Ruth Goodall, Zehava Grossman, Monick Lindenmeyer-Guimarães, Beatrice Hahn, Raph L Hamers, Osamah Hamouda, Ray Handema, Xiang He, Joshua Herbeck, David D Ho, Africa Holguin, Mina Hosseinipour, Gillian Hunt, Masahiko Ito, Mohamed Ali Bel Hadj Kacem, Erin Kahle, Pontiano Kaleebu Kaleebu, Marcia Kalish, Adeeba Kamarulzaman, Chun Kang, Phyllis Kanki, Edward Karamov, Jean-Claude Karasi, Kayitesi Kayitenkore, Tony Kelleher, Dwip Kitayaporn, Leondios G Kostrikis, Claudia Kucherer, Claudia Lara, Thomas Leitner, Kirsi Liitsola, Jai Lingappa, Marek Linka, Ivette Lorenzana de Rivera, Vladimir Lukashov, Shlomo Maayan, Luzia Mayr, Francine McCutchan, Nicolas Meda, Elisabeth Menu, Fred Mhalu, Doreen Mloka, John L Mokili, Brigitte Montes, Orna Mor, Mariza Morgado, Fausta Mosha, Awatef Moussi, James Mullins, Rafael Najera, Mejda Nasr, Nicaise Ndembi, Joel R Neilson, Vivek R Nerurkar, Florian Neuhann, Claudine Nolte, Vlad Novitsky, Philippe Nyambi, Marianna Ofner, Fem J Paladin, Anna Papa, Jean Pape, Neil Parkin, Chris Parry, Martine Peeters, Alexandra Pelletier, Lucía Pérez-Álvarez, Deenan Pillay, Angie Pinto, Trinh Duy Quang, Cecilia Rademeyer, Filimone Raikanikoda, Mark A Rayfield, Jean-Marc Reynes, Tobias Rinke de Wit, Kenneth E Robbins, Morgane Rolland, Christine Rousseau, Jesus Salazar-Gonzales, Hanan Salem, Mika Salminen, Horacio Salomon, Paul Sandstrom, Mario L Santiago, Abdoulaye D Sarr, Bryan Schroeder, Michel Segondy, Philippe Selhorst, Sylvester Sempala, Jean Servais, Ansari Shaik, Yiming Shao, Amine Slim, Marcelo A Soares, Elijah Songok, Debbie Stewart, Julie Stokes, Shambavi Subbarao, Ruengpung Sutthent, Jun Takehisa, Amilcar Tanuri, Kok Keng Tee, Kiran Thapa, Michael Thomson, Tyna Tran, Willy Urassa, Hiroshi Ushijima, Philippevan de Perre, Guidovan der Groen, Kristel van Laethem, Joep van Oosterhout, Ard van Sighem, Eric van Wijngaerden, Anne-Mieke Vandamme, Jurgen Vercauteren, Nicole Vidal, Lesley Wallace, Carolyn Williamson, Dawit Wolday, Jianqing Xu, Chunfu Yang, Linqi Zhang, and Rong Zhang

Subjects
0301 basic medicine, Serotype, Genotype, Genotyping Techniques, 030106 microbiology, DIVERSITY, MULTICENTER, VACCINE, HIV Infections, Genome, Viral, Biology, Global Health, Serogroup, SUBTYPES, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, INFECTION, Genetic variation, Global health, Humans, HIV vaccine, Serotyping, AIDS Vaccines, Science & Technology, Molecular epidemiology, Genetic Variation, Subtyping, 3. Good health, Trend analysis, 030104 developmental biology, Infectious Diseases, 13. Climate action, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Life Sciences & Biomedicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None. ispartof: LANCET INFECTIOUS DISEASES vol:19 issue:2 pages:143-155 ispartof: location:United States status: published

Published
2018
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