scholarly journals Absence of Resistance Mutations in the Integrase Coding Region among ART-Experienced Patients in the Republic of the Congo

2021 ◽  
Vol 9 (11) ◽  
pp. 2355
Author(s):  
Ferdinand Emaniel Brel Got ◽  
Patricia Recordon-Pinson ◽  
Ghislain Loubano-Voumbi ◽  
Dagene Ebourombi ◽  
Marie-Lise Blondot ◽  
...  

Background: HIV infects around one hundred thousand patients in the Republic of the Congo. Approximately 25% of them receive an antiretroviral treatment; current first-line regimens include two NRTIs and one NNRTI, reverse transcriptase inhibitors. Recently, protease inhibitors (PIs) were also introduced as second-line therapy upon clinical signs of treatment failure. Due to the limited number of molecular characterizations and amount of drug resistance data available in the Republic of the Congo, this study aims to evaluate the prevalence of circulating resistance mutations within the pol region. Methods: HIV-positive, ART-experienced patients have been enrolled in four semi-urban localities in the Republic of the Congo. Plasma samples were collected, and viral RNA was extracted. The viral load for each patient was evaluated by RT-qPCR, following the general diagnostic procedures of the University Hospital of Bordeaux. Finally, drug resistance genotyping and phylogenetic analysis were conducted following Sanger sequencing of the pol region. Results: A high diversity of HIV-1 strains was observed with many recombinant forms. Drug resistance mutations in RT and PR genes were determined and correlated to HAART. Because integrase inhibitors are rarely included in treatments in the Republic of the Congo, the prevalence of integrase drug resistance mutations before treatment was also determined. Interestingly, very few mutations were observed. Conclusions: We confirmed a high diversity of HIV-1 in the Republic of the Congo. Most patients presented an accumulation of mutations conferring resistance against NRTIs, NNRTIs and PIs. Nonetheless, the absence of integrase mutations associated with drug resistance suggests that the introduction of integrase inhibitors into therapy will be highly beneficial to patients in the Republic of the Congo.

Sexual Health ◽  
2009 ◽  
Vol 6 (4) ◽  
pp. 305 ◽  
Author(s):  
Anna C. Hearps ◽  
Vicki Greengrass ◽  
Jennifer Hoy ◽  
Suzanne M. Crowe

Background: The integrase inhibitors (e.g. Raltegravir) are a new class of antiretroviral drugs that have recently become available for the treatment of patients with multi-drug resistant HIV-1 within Australia. The emergence of mutations that confer resistance to the integrase inhibitors has been observed in vivo; however, no commercial genotyping assay is currently available to screen for resistance to these drugs. Methods: The HIV-1 integrase gene was amplified from plasma-derived HIV-1 viral RNA via reverse transcription-polymerase chain reaction and genotype determined via population DNA sequencing. Drug resistance mutations and polymorphisms were detected using the Stanford University online HIV database. Assay sensitivity and reproducibility were determined using clinical and laboratory-derived samples. Results: Our in-house assay was capable of genotyping the integrase gene from all samples tested (n = 30) of HIV-1 subtypes B, C, D, F, CFR01_AE and CRF02_AG and can amplify the integrase region from plasma samples containing as few as 50 HIV RNA copies/mL. The assay is highly reproducible (average nucleotide concordance = 99.6%, n = 4) and is capable of detecting resistance-associated mutations. Conclusions:This assay is suitable for routine drug resistance screening of plasma samples from HIV-infected patients receiving integrase inhibitor antiretroviral drugs and also serves as a useful research tool.


2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  

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.


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 ◽  
...  

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Tomohiro Kotaki ◽  
Siti Qamariyah Khairunisa ◽  
Adiana Mutamsari Witaningrum ◽  
Muhammad Qushai Yunifiar M ◽  
Septhia Dwi Sukartiningrum ◽  
...  

Author(s):  
Flávia Jacqueline Almeida ◽  
Rosangela Rodrigues ◽  
Mayra Simioni Zaparoli ◽  
Eitan Naaman Berezin ◽  
Marco Aurélio Palazzi Sáfadi ◽  
...  

Author(s):  
Myuki Esashika Crispim ◽  
Monica Nogueira da Guarda Reis ◽  
Mariane Martins de Araujo Stefani

2011 ◽  
Vol 15 (11) ◽  
pp. e764-e768 ◽  
Author(s):  
Moises A. Huaman ◽  
Javier Aguilar ◽  
Dwayne Baxa ◽  
Alicia Golembieski ◽  
Indira Brar ◽  
...  

2009 ◽  
Vol 10 (Suppl 8) ◽  
pp. S10 ◽  
Author(s):  
Omar Haq ◽  
Ronald M Levy ◽  
Alexandre V Morozov ◽  
Michael Andrec

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