Drug resistance mutations and newly recognized treatment-related substitutions in the HIV-1 protease gene: Prevalence and associations with drug exposure and real or virtual phenotypic resistance to protease inhibitors in two clinical cohorts of antiretroviral experienced patients

2004 ◽  
Vol 74 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Carlo Torti ◽  
Eugenia Quiros-Roldan ◽  
Laura Monno ◽  
Andrea Patroni ◽  
Annalisa Saracino ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Protease Inhibitors ◽  
Drug Exposure ◽  
Protease Gene ◽  
Resistance Mutations ◽  
Phenotypic Resistance ◽  
Drug Resistance Mutations ◽  
Hiv 1

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 Transient HIV-1 Gag–protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations

2016 ◽  
Vol 113 (44) ◽  
pp. 12456-12461 ◽  
Author(s):  
Lalit Deshmukh ◽  
John M. Louis ◽  
Rodolfo Ghirlando ◽  
G. Marius Clore
Keyword(s):  
Drug Resistance ◽  
Protease Inhibitors ◽  
Specific Antigen ◽  
Paramagnetic Nmr ◽  
Cleavage Sites ◽  
Resistance Mutations ◽  
Gag Polyprotein ◽  
Intrinsically Disordered ◽  
Drug Resistance Mutations ◽  
Hiv 1

Cleavage of the group-specific antigen (Gag) polyprotein by HIV-1 protease represents the critical first step in the conversion of immature noninfectious viral particles to mature infectious virions. Selective pressure exerted by HIV-1 protease inhibitors, a mainstay of current anti–HIV-1 therapies, results in the accumulation of drug resistance mutations in both protease and Gag. Surprisingly, a large number of these mutations (known as secondary or compensatory mutations) occur outside the active site of protease or the cleavage sites of Gag (located within intrinsically disordered linkers connecting the globular domains of Gag to one another), suggesting that transient encounter complexes involving the globular domains of Gag may play a role in guiding and facilitating access of the protease to the Gag cleavage sites. Here, using large fragments of Gag, as well as catalytically inactive and active variants of protease, we probe the nature of such rare encounter complexes using intermolecular paramagnetic relaxation enhancement, a highly sensitive technique for detecting sparsely populated states. We show that Gag-protease encounter complexes are primarily mediated by interactions between protease and the globular domains of Gag and that the sites of transient interactions are correlated with surface exposed regions that exhibit a high propensity to mutate in the presence of HIV-1 protease inhibitors.

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

Drug resistance mutations in protease gene of HIV-1 subtype C infected patient population

VirusDisease ◽  
2021 ◽  
Author(s):  
Mohammad Misbah ◽  
Poonam Gupta ◽  
Gaurav Roy ◽  
Suresh Kumar ◽  
Mohammad Husain
Keyword(s):  
Drug Resistance ◽  
Patient Population ◽  
Infected Patient ◽  
Protease Gene ◽  
Resistance Mutations ◽  
Subtype C ◽  
Drug Resistance Mutations ◽  
Hiv 1

scholarly journals Prevalence of drug resistance mutations in HIV-1 protease gene from North India

2012 ◽  
Vol 12 (S1) ◽  
Author(s):  
Mohd Azam ◽  
Abida Malik ◽  
Meher Rizvi ◽  
Supriya Singh ◽  
Hanu Ram ◽  
...  
Keyword(s):  
Drug Resistance ◽  
North India ◽  
Protease Gene ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1

scholarly journals High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yury Oliveira Chaves ◽  
Flávio Ribeiro Pereira ◽  
Rebeca de Souza Pinheiro ◽  
Diego Rafael Lima Batista ◽  
Antônio Alcirley da Silva Balieiro ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Combined Antiretroviral Therapy ◽  
Hiv 1

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or B C mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic ( B PAN ), and 15.7% were Caribbean ( B CAR ). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used—for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN . Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

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