scholarly journals Primary HIV-1 resistance: Persistence of transmitted drug resistance mutations

2012 ◽  
Vol 64 (4) ◽  
pp. 1301-1309 ◽  
Author(s):  
Valentina Nikolic ◽  
D. Salemovic ◽  
Dj. Jevtovic ◽  
I. Pesic-Pavlovic ◽  
S. Zerjav ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Viral Fitness ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
High Level ◽  
Hiv 1 ◽  
Level Resistance

Transmitted drug resistance (TDR) is one of the consequences of the high variability of HIV-1. The widespread use of antiretroviral therapy for the treatment of HIV-1 infection results in a large circulating pool of resistant virus variants. It is known that TDR mutations can persist for extended periods and may pose an important problem to the overall success of antiretroviral therapy. Factors that determine the duration of continuous persistence of resistance-associated mutations are the number and type of these mutations and their impact on viral fitness. Here we describe the follow-up of a case study of prolonged persistence of resistance-associated mutations, namely RT mutations Q151M, K65KR and Y181C conferring an intermediate-to-high level resistance to multiple NRTIs and NNRTIs that lasted for seven years. The infection was caused by subtype G virus.

scholarly journals HIV-1 transmitted drug resistance mutations among antiretroviral therapy-Naïve individuals in Surabaya, Indonesia

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Tomohiro Kotaki ◽  
Siti Qamariyah Khairunisa ◽  
Adiana Mutamsari Witaningrum ◽  
Muhammad Qushai Yunifiar M ◽  
Septhia Dwi Sukartiningrum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1

scholarly journals Impaired Replication Capacity of Acute/Early Viruses in Persons Who Become HIV Controllers

2010 ◽  
Vol 84 (15) ◽  
pp. 7581-7591 ◽  
Author(s):  
Toshiyuki Miura ◽  
Zabrina L. Brumme ◽  
Mark A. Brockman ◽  
Pamela Rosato ◽  
Jennifer Sela ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Replication ◽  
Acute Infection ◽  
Viral Fitness ◽  
Replication Capacity ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv Controllers ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) controllers maintain viremia at <2,000 RNA copies/ml without antiretroviral therapy. Viruses from controllers with chronic infection were shown to exhibit impaired replication capacities, in part associated with escape mutations from cytotoxic-T-lymphocyte (CTL) responses. In contrast, little is known about viruses during acute/early infection in individuals who subsequently become HIV controllers. Here, we examine the viral replication capacities, HLA types, and virus sequences from 18 HIV-1 controllers identified during primary infection. g ag-protease chimeric viruses constructed using the earliest postinfection samples displayed significantly lower replication capacities than isolates from persons who failed to control viremia (P = 0.0003). Protective HLA class I alleles were not enriched in these early HIV controllers, but viral sequencing revealed a significantly higher prevalence of drug resistance mutations associated with impaired viral fitness in controllers than in noncontrollers (6/15 [40.0%] versus 10/80 [12.5%], P = 0.018). Moreover, of two HLA-B57-positive (B57+) controllers identified, both harbored, at the earliest time point tested, signature escape mutations within Gag that likewise impair viral replication capacity. Only five controllers did not express “protective” alleles or harbor viruses with drug resistance mutations; intriguingly, two of them displayed typical B57 signature mutations (T242N), suggesting the acquisition of attenuated viruses from B57+ donors. These data indicate that acute/early stage viruses from persons who become controllers have evidence of reduced replication capacity during the initial stages of infection which is likely associated with transmitted or acquired CTL escape mutations or transmitted drug resistance mutations. These data suggest that viral dynamics during acute infection have a major impact on HIV disease outcome.

scholarly journals Transmitted Drug Resistance in Treatment-naïve HIV-Infected VCT clients in Taiwan, 2007–2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S423-S424
Author(s):  
Hung-Chin Tsai ◽  
I-Tzu Chen ◽  
Susan Shin-Jung Lee ◽  
Yao-Shen Chen
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Resistance Mutation ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Drug Resistance Testing ◽  
Subtype B ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Level Resistance

Abstract Background The transmission of drug-resistant HIV-1 strains might compromise the efficacy of antiretroviral treatment. The aim of this study was to monitor the prevalence of transmitted drug resistance (TDR) in Taiwan, where free highly active antiretroviral therapy (HAART) was provided since 1997. Methods A cohort study on TDR was conducted in antiretroviral therapy -naïve HIV-1 ¡Vinfected voluntary counseling and testing (VCT) clients from 2007 to 2016 in southern Taiwan. Genotypic drug resistance testing to PR/RT (pol gene) were determined by ViroSeqTM system and drug resistance testing to integrase inhibitors (INSTI) was done by in house PCR. Antiretroviral resistance was interpreted using the HIVdb program of the Stanford University HIV Drug Resistance Database. The patients classified as having low-level resistance, intermediate resistance and high-level resistance were defined as having drug resistance. Resistance-associated mutations were defined by the presence of at least one mutation included in the 2017 drug resistance mutation list of the International AIDS Society-USA consensus guidelines. Results A total of 29384 individuals received a free HIV anonymously screening test during 2007 to 2016. The positive rate for HIV-1 infection was 2%. Sequences were obtained from 407 individuals, of whom 90% were infected by MSM, and 10% were infected by heterosexually. Subtype B HIV-1 strains were found in 97%, subtype C in 0.3% and subtype CRF01_AE in 2.7%. A total of 6% was found to harbor drug resistance strains. The most common NRTI resistance associated mutation was D67N, M184V, K219N, Y118I and T215S/P. The most common NNRTI resistance associated mutation was Y181C, K103N, V179D and Y318F. No any one harbored resistance to INSTI inhibitors (n = 188). Conclusion The resistance prevalence (6%) in this study supported the WHO guideline to prescribe pol resistance testing before initiation of HAART therapy in the treatment naïve patients. Disclosures All authors: No reported disclosures.

Characteristics of drug resistance in HIV-1 CRF55_01B from ART-experienced patients in Guangdong, China

2020 ◽  
Vol 75 (7) ◽  
pp. 1925-1931 ◽  
Author(s):  
Yun Lan ◽  
Ruolei Xin ◽  
Weiping Cai ◽  
Xizi Deng ◽  
Linghua Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Susceptibility ◽  
Public Health Issue ◽  
Resistance Mutations ◽  
Acquired Drug Resistance ◽  
Low Level ◽  
High Level ◽  
Hiv 1 ◽  
Level Resistance ◽  
Epidemiological Information

Abstract Background HIV-1 acquired drug resistance (ADR) has become a critical clinical and public health issue. Recently, HIV-1 CRF55_01B has been found more frequently in the MSM population. Objective To investigate the characteristics of HIV-1 drug resistance mutations (DRMs) and the extent of changes in drug susceptibility among ART-experienced CRF55_01B-infected adults of Guangdong. Methods ADR was tested for immediately in CRF55_01B-infected patients with virological failure. Demographic and epidemiological information was collected. DRMs and antiretroviral susceptibility were interpreted using the Stanford University HIV Drug Resistance Database HIVdb program. Results Overall, 162 (4.78%) CRF55_01B isolates were identified from 2013 to 2018. Among DRMs, M184V (43.83%) was the most frequent NRTI DRM, followed by K65R (23.46%), and V179E (98.77%) was the most frequent NNRTI DRM, followed by K103N (47.53%) and Y181C (14.81%). According to the HIVdb program, 79.01% of the CRF55_01B-infected patients carried mutations conferring low-level or higher drug resistance to any of the three classes of ART drugs. Among PI DRMs, only one mutation affording low-level resistance to nelfinavir was found (0.62%). Among NRTI DRMs, a high proportion of high-level resistance to lamivudine (58.64%) and emtricitabine (58.02%) was found. As regards NNRTIs, more than 75% of patients carried efavirenz and nevirapine DRMs. The percentages of high-level resistance were 70.99%, 63.58%, 22.22%, 17.90% and 4.32% for nevirapine, efavirenz, rilpivirine, doravirine and etravirine, respectively. Conclusions High frequencies of DRMs and resistance were observed among CRF55_01B-infected patients failing ART in Guangdong, and interventions may be considered to minimize ecological contributions to ART.

scholarly journals Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 879
Author(s):  
Soo-Yon Rhee ◽  
Philip L. Tzou ◽  
Robert W. Shafer
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Temporal Trends ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Thymidine Analog ◽  
Art Practices ◽  
Hiv 1

In 2009, a list of nonpolymorphic HIV-1 drug resistance mutations (DRMs), called surveillance DRMs (SDRMs), was created to monitor transmitted drug resistance (TDR). Since 2009, TDR increased and antiretroviral therapy (ART) practices changed. We examined the changing prevalence of SDRMs and identified candidate SDRMs defined as nonpolymorphic DRMs present on ≥ 1 expert DRM list and in ≥0.1% of ART-experienced persons. Candidate DRMs were further characterized according to their association with antiretrovirals and changing prevalence. Among NRTI-SDRMs, tenofovir-associated mutations increased in prevalence while thymidine analog mutations decreased in prevalence. Among candidate NRTI-SDRMs, there were six tenofovir-associated mutations including three which increased in prevalence (K65N, T69deletion, K70G/N/Q/T). Among candidate NNRTI-SDRMs, six that increased in prevalence were associated with rilpivirine (E138K/Q, V179L, H221Y) or doravirine (F227C/L) resistance. With the notable exceptions of I47A and I50L, most PI-SDRMs decreased in prevalence. Three candidate PI-SDRMs were accessory darunavir-resistance mutations (L10F, T74P, L89V). Adding the candidate SDRMs listed above was estimated to increase NRTI, NNRTI, and PI TDR prevalence by 0.1%, 0.3%, and 0.3%, respectively. We describe trends in the prevalence of nonpolymorphic HIV-1 DRMs in ART-experienced persons. These data should be considered in decisions regarding SDRM list updates and TDR monitoring.

scholarly journals Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Bin Zhao ◽  
Minghui An ◽  
Wei Song ◽  
Xue Dong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Northeast China ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Shenyang City ◽  
Subtype B ◽  
Recent Hiv Infection ◽  
Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

scholarly journals Major drug resistance mutations to HIV-1 protease inhibitors (PI) among patients exposed to PI class failing antiretroviral therapy in São Paulo State, Brazil

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223210
Author(s):  
Giselle de Faria Romero Soldi ◽  
Isadora Coutinho Ribeiro ◽  
Cintia Mayumi Ahagon ◽  
Luana Portes Ozório Coelho ◽  
Gabriela Bastos Cabral ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Protease Inhibitors ◽  
Sao Paulo ◽  
Resistance Mutations ◽  
Paulo State ◽  
Drug Resistance Mutations ◽  
São Paulo State ◽  
Major Drug ◽  
Hiv 1

scholarly journals Late presentation and transmitted drug resistance mutations in new HIV-1 diagnoses in Detroit

2011 ◽  
Vol 15 (11) ◽  
pp. e764-e768 ◽  
Author(s):  
Moises A. Huaman ◽  
Javier Aguilar ◽  
Dwayne Baxa ◽  
Alicia Golembieski ◽  
Indira Brar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Late Presentation ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

scholarly journals Transmitted drug resistance mutations and subtype diversity among HIV-1 sero-positive voluntary blood donors in Accra, Ghana

2020 ◽  
Author(s):  
Billal Musah Obeng ◽  
Evelyn Yayra Bonney ◽  
Lucy Asamoah-Akuoko ◽  
Nicholas Israel Nii-Trebi ◽  
Gifty Mawuli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Donors ◽  
Transmitted Drug Resistance ◽  
Nucleotide Sequencing ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Major Drug ◽  
Hiv 1

Abstract Background: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of ART among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations and subtype diversity among HIV-1 sero-positive blood donors in Accra, Ghana was characterized.Methods: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by serology as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbor-joining tree with the Kimura’s 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0).Results: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 50% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. Conclusion: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis suggest possible subtype importation. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.

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