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      Pretreatment drug resistance in people living with HIV: A large retrospective cohort study in Chongqing, China

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          Abstract

          Objectives

          The emergence of pretreatment drug resistance (PDR) caused by increased usage of antiretroviral therapy (ART) represents a significant challenge to HIV management. In this study, we evaluated the prevalence of PDR in people living with HIV (PLWH) in Chongqing, China.

          Methods

          We retrospectively collected the data of 1110 ART‐naïve PLWH in Chongqing from January 1, 2018 to June 30, 2021. HIV‐1 genotypes and drug resistance were analyzed using the HIV‐1 pol sequence. Risk factors associated with PDR were evaluated via the logistic regression model.

          Results

          Nine genotypes were detected among 1110 participants, with CRF07_BC (55.68%) being the dominant genotype, followed by CRF01_AE (21.44%), CRF08_BC (14.14%), and other genotypes (8.74%). Of all the participants, 24.14% exhibited drug resistance mutations (DRMs). The predominant DRMs for non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were V179D/E/A/DIN (13.60%) and M184V/I (1.44%), respectively, whereas only two major DRMs (M46L and I54L) were identified for protease inhibitors (PIs). The total prevalence of PDR was 10.54%, with 2.43%, 7.66%, and 1.71% participants exhibiting PDR to NRTIs, NNRTIs, and PIs, respectively. Furthermore, female PLWH, delays in ART initiation, and the CRF08_BC genotype were associated with a higher risk of PDR.

          Conclusions

          Our study provides the first large cohort data on the prevalence of PDR in Chongqing, China. HIV‐1 genotypes are diverse and complex, with a moderate level of PDR, which does not reach the threshold for the initiation of a public health response. Nevertheless, continuous surveillance of PDR is both useful and advisable.

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          Most cited references24

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          HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

          Summary Background Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs. Methods This study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions. Findings We identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5–15·9) in southern Africa, 10·1% (5·1–19·4) in eastern Africa, 7·2% (2·9–16·5) in western and central Africa, and 9·4% (6·6–13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly increases in the odds of pretreatment drug resistance were 23% (95% CI 16–29) in southern Africa, 17% (5–30) in eastern Africa, 17% (6–29) in western and central Africa, 11% (5–18) in Latin America and the Caribbean, and 11% (2–20) in Asia. Estimated increases in the absolute prevalence of pretreatment drug resistance between 2015 and 2016 ranged from 0·3% in Asia to 1·8% in southern Africa. Interpretation Pretreatment drug resistance is increasing at substantial rate in LMICs, especially in sub-Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near WHO's 10% threshold for changing first-line ART in southern and eastern Africa and Latin America, underscoring the need for routine national HIV drug-resistance surveillance and review of national policies for first-line ART regimen composition. Funding Bill & Melinda Gates Foundation and World Health Organization.
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            Web resources for HIV type 1 genotypic-resistance test interpretation.

            Interpreting the results of plasma human immunodeficiency virus type 1 (HIV-1) genotypic drug-resistance tests is one of the most difficult tasks facing clinicians caring for HIV-1-infected patients. There are many drug-resistance mutations, and they arise in complex patterns that cause varying levels of drug resistance. In addition, HIV-1 exists in vivo as a virus population containing many genomic variants. Genotypic-resistance testing detects the drug-resistance mutations present in the most common plasma virus variants but may not detect drug-resistance mutations present in minor virus variants. Therefore, interpretation systems are necessary to determine the phenotypic and clinical significance of drug-resistance mutations found in a patient's plasma virus population. We describe the scientific principles of HIV-1 genotypic-resistance test interpretation and the most commonly used Web-based resources for clinicians ordering genotypic drug-resistance tests.
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              HIV-1 drug resistance and resistance testing.

              The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases.
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                Author and article information

                Contributors
                yaokaichen@hotmail.com
                Journal
                HIV Med
                HIV Med
                10.1111/(ISSN)1468-1293
                HIV
                HIV Medicine
                John Wiley and Sons Inc. (Hoboken )
                1464-2662
                1468-1293
                15 March 2022
                March 2022
                : 23
                : Suppl 1 , Snapshot of clinical problems among people living with HIV in China ( doiID: 10.1111/hiv.v23.s1 )
                : 95-105
                Affiliations
                [ 1 ] Division of Infectious Diseases Chongqing Public Health Medical Center Chongqing China
                [ 2 ] Department of Clinical Laboratory Chongqing Public Health Medical Center Chongqing China
                Author notes
                [*] [* ] Correspondence

                Yao‐Kai Chen, Division of Infectious Diseases, Chongqing Public Health Medical Center, 109 Baoyu Road, Shapingba District, Chongqing, 400036, China.

                Email: yaokaichen@ 123456hotmail.com

                Author information
                https://orcid.org/0000-0002-4369-057X
                https://orcid.org/0000-0002-2134-3809
                https://orcid.org/0000-0001-9327-9546
                https://orcid.org/0000-0002-2762-1056
                https://orcid.org/0000-0001-7423-6786
                https://orcid.org/0000-0002-0342-4381
                https://orcid.org/0000-0002-0587-2313
                https://orcid.org/0000-0003-2812-3275
                https://orcid.org/0000-0002-8210-6217
                https://orcid.org/0000-0002-1926-4511
                https://orcid.org/0000-0002-3229-0108
                Article
                HIV13253
                10.1111/hiv.13253
                9311700
                35293098
                dc8ee85e-ed9e-4b47-9af2-247fbc6d7a7e
                © 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 14 January 2022
                Page count
                Figures: 3, Tables: 3, Pages: 11, Words: 5240
                Categories
                Original Research
                Snapshot of clinical problems among people living with HIV in China
                Original Research
                Custom metadata
                2.0
                March 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:25.07.2022

                Infectious disease & Microbiology
                genotype,hiv‐1,mutation,pretreatment drug resistance,risk factors

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