scholarly journals HIV-1 resistance profile in plasma and peripheral blood lymphocytes in a group of naive patients

2012 ◽  
Vol 64 (4) ◽  
pp. 1261-1270 ◽  
Author(s):  
Marina Siljic ◽  
Dubravka Salemovic ◽  
Dj. Jevtovic ◽  
Ivana Pesic-Pavlovic ◽  
Sonja Zerjav ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Viral Rna ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Resistance Profile ◽  
Proviral Dna ◽  
Drug Resistance Mutations ◽  
Hiv 1

Transmitted HIV-1 drug resistance (TDR) is a persisting problem, even though the prevalence of primary resistance may remain stable or start to decline. Proviral DNA detectable in peripheral blood mononuclear cells (PBMCs) is a reservoir of drug resistant viral variants and could be an alternative marker to viral RNA for the detection of drug resistance mutations. The aim of this study was to compare the HIV-1 resistance profile between plasma viral RNA and proviral DNA in a group of untreated patients. Thirty-one HIV-1 seropositive patients without prior ARV treatment were included in the study. The presence of non-polymorphic drug resistance mutations was identified in 10 cases in proviral DNA and in 11 cases in plasma according to different scoring systems. Our results show a similar resistance profile between plasma RNA and proviral DNA, but with some discordances present. The sequencing of proviral DNA could provide useful additional information with regard to primary resistance.

scholarly journals Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens

2019 ◽  
Vol 6 (3) ◽  
Author(s):  
Justin De La Cruz ◽  
Saran Vardhanbhuti ◽  
Malaya K Sahoo ◽  
Robert Rovner ◽  
Ronald J Bosch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Deoxyribonucleic Acid ◽  
Mononuclear Cells ◽  
Virologic Failure ◽  
Resistance Mutations ◽  
Proviral Dna ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus

Abstract Background Efavirenz (EFV)-based regimens select broad drug resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs), limiting the effectiveness of EFV and other NNRTIs. The duration, persistence, and decay of drug resistance mutations (DRMs) in the proviral reservoir is not well defined. Methods Participants with virologic failure of EFV-based regimens and drug-resistant viremia with the K103N mutation in plasma ribonucleic acid (RNA) were identified from AIDS Clinical Trials Group (ACTG) studies A364 and A5095. These individuals received a second-line, boosted protease inhibitor-based regimen with suppression of viremia for up to10 years during long-term follow-up (median = 3.6 years; interquartile range, 2.1–6.9 years). Proviral deoxyribonucleic acid (DNA) from cryopreserved peripheral blood mononuclear cells was sequenced to identify the persistence of DRM. Results Twenty-eight participants from ACTG 364 and ACTG 5095 were evaluated. Sanger sequencing of proviral DNA detected K103N as well as additional reverse-transcriptase inhibitor (RTI) mutations. Ultradeep sequencing confirmed persistence of K103N in 71% of participants with minimal decay over time. In an adjusted model including years since suppression, persistent proviral K103N was 2.6 times more likely (95% confidence interval, 1.0–6.4) per log10 higher human immunodeficiency virus RNA at EFV failure. Conclusions Persistence of RTI mutations in proviral DNA after virologic failure has implications for the effectiveness of future drug regimens and the recycling of RTI drugs.

scholarly journals Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study

Acta Naturae ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 78-86 ◽  
Author(s):  
O. A. Shadrina ◽  
T. S. Zatsepin ◽  
Yu. Yu. Agapkina ◽  
M. G. Isaguliants ◽  
M. B. Gottikh
Keyword(s):  
Drug Resistance ◽  
Comparative Study ◽  
Gene Mutations ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
The Impact ◽  
Hiv 1

Integration of human immunodeficiency virus (HIV-1) DNA into the genome of an infected cell is one of the key steps in the viral replication cycle. The viral enzyme integrase (IN), which catalyzes the integration, is an attractive target for the development of new antiviral drugs. However, the HIV-1 therapy often results in the IN gene mutations inducing viral resistance to integration inhibitors. To assess the impact of drug resistance mutations on the activity of IN of HIV-1 subtype A strain FSU-A, which is dominant in Russia, variants of the consensus IN of this subtype containing the primary resistance mutations G118R and Q148K and secondary compensatory substitutions E138K and G140S were prepared and characterized. Comparative study of these enzymes with the corresponding mutants of IN of HIV-1 subtype B strains HXB-2 was performed. The mutation Q148K almost equally reduced the activity of integrases of both subtypes. Its negative effect was partially compensated by the secondary mutations E138K and G140S. Primary substitution G118R had different influence on the activity of proteins of the subtypes A and B, and the compensatory effect of the secondary substitution E138K also depended on the viral subtype. Comparison of the mutants resistance to the known strand transfer inhibitors raltegravir and elvitegravir, and a new inhibitor XZ-259 (a dihydro-1H-isoindol derivative), showed that integrases of both subtypes with the Q148K mutation were insensitive to raltegravir and elvitegravir but were effectively inhibited by XZ-259. The substitution G118R slightly reduced the efficiency of IN inhibition by raltegravir and elvitegravir and caused no resistance to XZ_259.

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.

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 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

Prevalence of Transmitted HIV-1 Drug Resistance Mutations in Children and Adolescents in São Paulo, Brazil

2012 ◽  
pp. 1
Author(s):  
Flávia Jacqueline Almeida ◽  
Rosangela Rodrigues ◽  
Mayra Simioni Zaparoli ◽  
Eitan Naaman Berezin ◽  
Marco Aurélio Palazzi Sáfadi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Children And Adolescents ◽  
Sao Paulo ◽  
São Paulo ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1

scholarly journals HIV-1 genetic diversity and drug resistance mutations in the northern Brazilian region

2021 ◽  
pp. 101596
Author(s):  
Myuki Esashika Crispim ◽  
Monica Nogueira da Guarda Reis ◽  
Mariane Martins de Araujo Stefani
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
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
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