scholarly journals Prevalence of and Viral Outcomes Associated with Primary HIV-1 Drug Resistance

2012 ◽  
Vol 6 (1) ◽  
pp. 181-187 ◽  
Author(s):  
SE Buskin ◽  
S Zhang ◽  
CS Thibault
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Statistical Power ◽  
Laboratory Data ◽  
Primary Resistance ◽  
Hiv Surveillance ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Primary, or transmitted, HIV antiretroviral resistance is an ongoing concern despite continuing development of new antiretroviral therapies. We examined HIV surveillance data, including both patient demographic characteristics and laboratory data, combined with HIV genotypic test results to evaluate the comprehensiveness of drug resistance surveillance, prevalence of primary drug resistance, and impact, if any, of primary resistance on population-based virological outcomes. The King County, WA Variant, Atypical, and Resistant HIV Surveillance (VARHS) system increased coverage of eligible genotypic testing – within three months of an HIV diagnosis among antiretroviral naïve individuals -- from – 15% in 2003 to 69% in 2010. VARHS under-represented females, Blacks, Native Americans, and injection drug users. Primary drug resistance was more common among males, individuals aged 20 – 29 years, men who had sex with men, and individuals with an initial CD4+ lymphocyte count of 200 cells/µL and higher. High level resistance to two or three antiretroviral classes declined over time. Over 90% of sequences were HIV-1 subtype B. The proportion of individuals with a most recent viral load (closest to April 2011) that was undetectable (<50 copies/mL) was not statistically significantly associated with primary drug resistance. This was true for both number and type of antiretroviral drug class; although small numbers of specimens with drug resistance may have limited our statistical power. In summary, although we found disparities in testing coverage and prevalence of drug resistance, we were unable to detect a significantly deleterious impact of primary drug resistance based on a most recent viral load.

Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China

2020 ◽  
Vol 18 (3) ◽  
pp. 210-218
Author(s):  
Guolong Yu ◽  
Yan Li ◽  
Xuhe Huang ◽  
Pingping Zhou ◽  
Jin Yan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Phylogenetic Analyses ◽  
Resistance Mutations ◽  
Protease Inhibition ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

scholarly journals P17.28 Assessment of hiv-1 primary drug resistance mutations in antiretroviral therapy-naive cases in morocco

2015 ◽  
Vol 91 (Suppl 2) ◽  
pp. A233.3-A234
Author(s):  
H Eloudyi ◽  
S Lemrabet ◽  
M Malmoussi ◽  
Z Ouagari ◽  
E Elharti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

scholarly journals Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity

2015 ◽  
Vol 89 (20) ◽  
pp. 10482-10488 ◽  
Author(s):  
Kaitlin Anstett ◽  
Robert Fusco ◽  
Vincent Cutillas ◽  
Thibault Mesplède ◽  
Mark A. Wainberg
Keyword(s):  
Drug Resistance ◽  
Rescue Therapy ◽  
Resistance Mutation ◽  
Viral Infectivity ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Subtype B ◽  
Compensatory Mutations ◽  
Hiv 1 ◽  
Level Resistance

ABSTRACTWe have previously shown that the addition of the raltegravir/elvitegavir (RAL/EVG) primary resistance mutation N155H to the R263K dolutegravir (DTG) resistance mutation partially compensated for the fitness cost imposed by R263K while also slightly increasing DTG resistancein vitro(K. Anstett, T. Mesplede, M. Oliveira, V. Cutillas, and M. A. Wainberg, J Virol89:4681–4684, 2015, doi:10.1128/JVI.03485-14). Since many patients failing RAL/EVG are given DTG as part of rescue therapy, and given that the N155H substitution often is found in combination with other compensatory resistance mutations in such individuals, we investigated the effects of multiple such substitutions within integrase (IN) on each of integrase function, HIV-1 infectivity, and levels of drug resistance. To this end, each of the L74M, E92Q, T97A, E157Q, and G163R substitutions were introduced into NL4.3 subtype B HIV-1 vectors harboring N155H and R263K in tandem [termed NL4.3IN(N155H/R263K)]. Relevant recombinant integrase enzymes also were expressed, and purified and biochemical assays of strand transfer efficiency as well as viral infectivity and drug resistance studies were performed. We found that the addition of T97A, E157Q, or G163R somewhat improved the affinity of INN155H/R263Kfor its target DNA substrate, while the presence of L74M or E92Q had a negative effect on this process. However, viral infectivity was significantly decreased from that of NL4.3IN(N155H/R263K)after the addition of each tertiary mutation, and no increases in levels of DTG resistance were observed. This work shows that the compensatory mutations that evolve after N155H under continued DTG or RAL/EVG pressure in patients are unable to improve either enzyme efficiency or viral infectivity in an N155H/R263K background.IMPORTANCEIn contrast to other drugs, dolutegravir has not selected for resistance in HIV-positive individuals when used in first-line therapy. We had previously shown that HIV containing the primary raltegravir/elvitegravir resistance substitution N155H could select for R263K under dolutegravir pressure and that this virus was fit and displayed low-level resistance to dolutegravir (Anstett et al., J Virol89:4681–4684). Therefore, the current study aimed to uncover whether accessory mutations that appear after N155H in response to raltegravir/elvitegravir were compatible with N155H and R263K. We found, however, that the addition of a third mutation negatively impacted both the enzyme and the virus in terms of activity and infectivity without large shifts in integrase inhibitor resistance. Thus, it is unlikely that these substitutions would be selected under dolutegravir pressure. These data support the hypothesis that primary resistance against DTG cannot evolve through RAL/EVG resistance pathways and that the selection of R263K leads HIV into an evolutionary dead-end.

scholarly journals HIV-1 Subtype Diversity and Prevalence of Primary Drug Resistance in a Single-Center Pediatric Cohort in Germany

Intervirology ◽  
2016 ◽  
Vol 59 (5-6) ◽  
pp. 301-306 ◽  
Author(s):  
Jennifer Neubert ◽  
Nadja Michalsky ◽  
Hans-Jürgen Laws ◽  
Arndt Borkhardt ◽  
Björn Jensen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Single Center ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

scholarly journals MOLECULAR-EPIDEMIOLOGICAL CHARACTERISTICS OF HIV1 VARIANTS CIRCULATING IN THE JEWISH AUTONOMOUS REGION TERRITORY

2019 ◽  
Vol 10 (4) ◽  
pp. 90-99 ◽  
Author(s):  
V. O. Kotova ◽  
O. E. Trotsenko ◽  
L. A. Balakhontseva ◽  
E. A. Bazykina ◽  
O. A. Yanovich ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutations ◽  
Prevalence Index ◽  
Epidemiological Analysis ◽  
Autonomous Region ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Epidemiological Characteristics ◽  
Hiv 1

Objective: to perform a molecular-epidemiological analysis of HIV-1 variants circulating in the Jewish autonomous region territory. Materials and methods. The research included 58 patients with HIV-infection. Amplified pol-gene fragments were used as a template to detect drug resistance mutations by Sanger sequencing (AmpliSens® HIV-Resist-Seq). Pol-gene is coding protease and a part of reverse transcriptase of HIV-1. Phylogenetic analysis was performed using MEGA version 6.0 program. Results: the research revealed an insignificant prevalence of HIV-1 СRF63_02A1 recombinant form. It was registered in 25 patients (44,6%). Sub-subtype A6 was identified in 23 HIV-positive people (41,1%). Subtype B was revealed in 6 cases (10,7%), subtype С — in two cases (3,6%). Primary drug resistance mutations were identified in 9 patients that were undergoing antiretroviral treatment. This dictates the necessity to change the treatment regimen in the specified patients. The prevalence index of drug resistance mutations in naïve patients equaled to 3,8%.

Alarming rate of transmitted drug resistance mutations and genetic diversity in newly HIV-1-infected patients in Benin

2020 ◽  
Author(s):  
Edmond Tchiakpe ◽  
Rene K Keke ◽  
Nicole Vidal ◽  
Clément Ahoussinou ◽  
Olga Sekpe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Resistance Rate ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
High Genetic Diversity ◽  
Drug Resistance Mutations ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Abstract BackgroundSeventeen years after the start of the IBAARV (Beninese initiative for access to antiretrovirals), transmitted drug resistance mutations in ARV naïve patients and HIV-1 genetic diversity were investigated in Benin.Methods353 plasma samples were collected between October and December 2017 in nineteen facilities care in Benin from HIV-1 positive and ARV naive individuals. Pol (protease + partial RT) region was amplified and sequenced in 248 samples.ResultsDrug resistance mutations were detected in (27/248; 10.9%) according to the WHO SDRM 2009 list, with predominance of mutations directed to NNRTIs drugs (24/248; 10%).Phylogenetic and recombination analyses showed a predominance of CRF02_AG strains (165/248; 66.5%) and a high genetic diversity with five other variants and 39 URFs (15.7%) which contained portions of strains that co-circulate in Benin. Eight recent transmission chains revealed active ongoing transmission of HIV-1 strains among ARV naïve patients.ConclusionsOur study showed a high primary drug resistance rate and a complex genetic diversity. Regular monitoring of primary drug resistance is required to adapt HIV-1 treatment strategies and adoption of new WHO recommendations in Benin.

scholarly journals Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Juan Pablo Rodriguez-Auad ◽  
Othon Rojas-Montes ◽  
Angelica Maldonado-Rodriguez ◽  
Ma. Teresa Alvarez-Muñoz ◽  
Onofre Muñoz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Attractive Alternative ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Resource Limited Settings ◽  
Middle Income ◽  
Subtype B ◽  
Resource Limited ◽  
Hiv 1

Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10copies/mL in liquid plasma and 4.1 log10copies/mL in DPS, with a correlation coefficient ofR= 0.83. A 1.1 kb fragment of HIVpolcould be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1polsequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

scholarly journals Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

2014 ◽  
Vol 8 (01) ◽  
pp. 079-085 ◽  
Author(s):  
Mohd Azam ◽  
Abida Malik ◽  
Meher Rizvi ◽  
Arvind Rai
Keyword(s):  
Drug Resistance ◽  
Protease Inhibitors ◽  
Resistance Testing ◽  
Protease Gene ◽  
Resistance Mutations ◽  
Subtype C ◽  
Primary Resistance ◽  
Primary Drug Resistance ◽  
Treatment Naïve ◽  
Hiv 1

Introduction: This study aimed to evaluate the prevalence of resistance mutations in the protease gene of HIV-1 strains isolated from north Indian antiretroviral (ARV) treatment-naive patients and to assess the phylogenetic relatedness of these strains with known HIV-1 strains. Methodology: Fifty-four HIV-1 strains isolated from treatment-naive patients (n = 54) were included in this study. Resistance genotyping for the protease gene was performed using semi-nested PCR and DNA sequencing. The sequences were aligned (ClustalW) and a phylogenetic tree was built (MEGA 4 software). Drug resistance (DR) pattern was analyzed using the Stanford HIV-DR database and the IAS-USA mutation list. For subtyping purposes, all the nucleotide sequences were submitted to the REGA HIV-1 subtyping tool version 2.0l. Results: All the strains (100%) were found to belong to the C subtype and to harbor at least two secondary mutations in the protease gene. The most frequent mutations were H69K and I93L (52 of 52 strains), followed by I15V (80.7%), L19I (69.2%), M36I (67.3%), R41K (94.2%), L63P (61.5%), and L89M (82.7%). Conclusion: This study confirms that HIV-1 subtype C predominates in northern India. Protease secondary mutations associated with drug resistance to protease inhibitors (PIs) were present with high frequency in the HIV-1 C subtype strains isolated from north Indian ARV treatment-naive patients, but no primary resistance mutations were found in this region. We suggest that resistance testing in HIV-1 infected patients should ideally be performed before the initiation of therapy to tailor the treatment for the individual to achieve the optimal therapeutic outcome

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