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      HIV drug resistance in persons who inject drugs enrolled in an HIV prevention trial in Indonesia, Ukraine, and Vietnam: HPTN 074

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          Abstract

          Background

          Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment.

          Methods

          HPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment.

          Results

          Fifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm.

          Conclusions

          In HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART.

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          Most cited references25

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          HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage.

          Previous reviews have examined the existence of HIV prevention, treatment, and care services for injecting drug users (IDUs) worldwide, but they did not quantify the scale of coverage. We undertook a systematic review to estimate national, regional, and global coverage of HIV services in IDUs. We did a systematic search of peer-reviewed (Medline, BioMed Central), internet, and grey-literature databases for data published in 2004 or later. A multistage process of data requests and verification was undertaken, involving UN agencies and national experts. National data were obtained for the extent of provision of the following core interventions for IDUs: needle and syringe programmes (NSPs), opioid substitution therapy (OST) and other drug treatment, HIV testing and counselling, antiretroviral therapy (ART), and condom programmes. We calculated national, regional, and global coverage of NSPs, OST, and ART on the basis of available estimates of IDU population sizes. By 2009, NSPs had been implemented in 82 countries and OST in 70 countries; both interventions were available in 66 countries. Regional and national coverage varied substantially. Australasia (202 needle-syringes per IDU per year) had by far the greatest rate of needle-syringe distribution; Latin America and the Caribbean (0.3 needle-syringes per IDU per year), Middle East and north Africa (0.5 needle-syringes per IDU per year), and sub-Saharan Africa (0.1 needle-syringes per IDU per year) had the lowest rates. OST coverage varied from less than or equal to one recipient per 100 IDUs in central Asia, Latin America, and sub-Saharan Africa, to very high levels in western Europe (61 recipients per 100 IDUs). The number of IDUs receiving ART varied from less than one per 100 HIV-positive IDUs (Chile, Kenya, Pakistan, Russia, and Uzbekistan) to more than 100 per 100 HIV-positive IDUs in six European countries. Worldwide, an estimated two needle-syringes (range 1-4) were distributed per IDU per month, there were eight recipients (6-12) of OST per 100 IDUs, and four IDUs (range 2-18) received ART per 100 HIV-positive IDUs. Worldwide coverage of HIV prevention, treatment, and care services in IDU populations is very low. There is an urgent need to improve coverage of these services in this at-risk population. UN Office on Drugs and Crime; Australian National Drug and Alcohol Research Centre, University of New South Wales; and Australian National Health and Medical Research Council. Copyright 2010 Elsevier Ltd. All rights reserved.
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            A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences.

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              Risk of HIV-1 transmission for parenteral exposure and blood transfusion: a systematic review and meta-analysis.

              The role of iatrogenic transmission within the HIV/AIDS pandemic remains contentious. Estimates of the risk of HIV transmission from injections and blood transfusions are required to inform appropriate prevention policy. Systematic review and meta-analysis of the literature on HIV-1 infectivity for parenteral transmission and blood transfusion. All identified studies with relevant transmission probability estimates up to May 2005 were included. When appropriate, summary estimates for accidental percutaneous and blood product exposures were derived. Infectivity estimates following a needlestick exposure ranged from 0.00 to 2.38% [weighted mean, 0.23%; 95% confidence interval (CI), 0.00-0.46%; n = 21]. Three estimates of infectivity per intravenous drug injection ranged from 0.63 to 2.4% (median, 0.8%); a summary estimate could not be calculated. The quality of the only estimate of infectivity per contaminated medical injection (1.9-6.9%) was assessed. Instead we propose a range of 0.24-0.65%. Infectivity estimates for confirmed contaminated blood transfusions range from 88.3 to 100.0% (weighted mean, 92.5%; 95% CI, 89.0-96.1%; n = 6). Infectivity estimates for infected blood transfusions are larger than for other modes of HIV transmission. Few studies on transmission risk per contaminated injection were found. However, transmission risk per needlestick injury, where needles are more likely to be rinsed or disinfected between recipients (especially for medical injections), may be representative of non-intravenous medical injections and lower than the risk from intravenous injections, which are likely to be deeper and to involve more fluids. Further work is needed to better estimate transmission probability related to contaminated injections and its likely contribution to overall HIV transmission.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Project administrationRole: ValidationRole: Writing – review & editing
                Role: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 October 2019
                2019
                : 14
                : 10
                : e0223829
                Affiliations
                [1 ] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
                [2 ] Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
                [3 ] Frontier Science Foundation, Amherst, NY, United States of America
                [4 ] Science Facilitation Department, Durham, NC, United States of America
                [5 ] University of North Carolina Vietnam, Hanoi, Vietnam
                [6 ] Gromashevsky Institute for Epidemiology and Infectious Diseases of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
                [7 ] University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
                [8 ] Department of Health Behavior, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America
                [9 ] Ukrainian Institute of Public Health Policy, Kyiv, Ukraine
                [10 ] Departments of Hematology, Medical Oncology, and Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
                [11 ] Department of Medicine, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC, United States of America
                [12 ] Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH, United States of America
                International AIDS Vaccine Initiative, UNITED STATES
                Author notes

                Competing Interests: We have read the journal's policy. None of the authors has a financial or personal relationship with other people or organizations that could inappropriately influence (bias) their work. Dr. Eshleman has collaborated on research studies with investigators from Abbott Diagnostics; Abbott Diagnostics provided reagents for some of those studies. Dr. Eshleman did not receive any funding or other support from Abbott Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-6394-6878
                http://orcid.org/0000-0003-3143-9000
                http://orcid.org/0000-0003-1174-9263
                http://orcid.org/0000-0001-7689-4002
                http://orcid.org/0000-0002-1934-7827
                http://orcid.org/0000-0002-4587-791X
                Article
                PONE-D-19-07824
                10.1371/journal.pone.0223829
                6786608
                31600343
                d8f25330-9ff6-47b0-b982-455624aa59a9
                © 2019 Palumbo et al

                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
                : 18 March 2019
                : 27 September 2019
                Page count
                Figures: 2, Tables: 4, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: UM1-AI068613
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: UM1-AI068617
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: UM1-AI068619
                This work was supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID, https://www.niaid.nih.gov/), National Institute on Drug Abuse (NIDA, https://www.drugabuse.gov/), and Office of AIDS Research, of the National Institutes of Health (NIH, https://www.oar.nih.gov/) [UM1-AI068613 to Eshleman; UM1-AI068617 to Donnell; and UM1-AI068619 to Cohen/El-Sadr]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                All FASTA files were submitted to GenBank (accession numbers: MK228137-MK228585).

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