scholarly journals Epidemiological and Molecular Characteristics of HIV-1 Infection in a Sample of Men Who Have Sex With Men in Brazil: Phylogeography of Major Subtype B and F1 Transmission Clusters

2020 ◽  
Vol 11 ◽  
Author(s):  
Ágabo Macêdo da Costa e Silva ◽  
Mônica Nogueira da Guarda Reis ◽  
Thaís Augusto Marinho ◽  
Nara Rúbia de Freitas ◽  
Sheila Araújo Teles ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
The State ◽  
Enzyme Linked Immunosorbent Assay ◽  
Molecular Characteristics ◽  
Resistance Mutations ◽  
Subtype B ◽  
Sex With Men ◽  
Hiv 1

This study describes human immunodeficiency virus 1 (HIV-1) prevalence, associated factors, viral genetic diversity, transmitted drug resistance (TDR), and acquired drug resistance mutations (DRM) among a population of 522 men who have sex with men (MSM) recruited by the respondent-driven sampling (RDS) method, in Goiânia city, the capital of the State of Goiás, Central-Western Brazil. All serum samples were tested using a four-generation enzyme-linked immunosorbent assay (ELISA), and reactive samples were confirmed by immunoblotting. Plasma RNA or proviral DNA was extracted, and partial polymerase (pol) gene including the protease/reverse transcriptase (PR/RT) region was amplified and sequenced. HIV-1 subtypes were identified by phylogenetic inference and by bootscan analysis. The time and location of the ancestral strains that originated the transmission clusters were estimated by a Bayesian phylogeographic approach. TDR and DRM were identified using the Stanford databases. Overall, HIV-1 prevalence was 17.6% (95% CI: 12.6–23.5). Self-declared black skin color, receptive anal intercourse, sex with drug user partner, and history of sexually transmitted infections were factors associated with HIV-1 infection. Of 105 HIV-1-positive samples, 78 (74.3%) were sequenced and subtyped as B (65.4%), F1 (20.5%), C (3.8%), and BF1 (10.3%). Most HIV-1 subtype B sequences (67%; 34 out of 51) branched within 12 monophyletic clusters of variable sizes, which probably arose in the State of Goiás between the 1980s and 2010s. Most subtype F1 sequences (n = 14, 88%) branched in a single monophyletic cluster that probably arose in Goiás around the late 1990s. Among 78 samples sequenced, three were from patients under antiretroviral therapy (ART); two presented DRM. Among 75 ART-naïve patients, TDR was identified in 13 (17.3%; CI 95%: 9.6–27.8). Resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) predominated (14.7%), followed by nucleoside reverse transcriptase inhibitor (NRTI) mutations (5.3%) and protease inhibitor (PI) mutations (1.3%). This study shows a high prevalence of HIV-1 associated with sexual risk behaviors, high rate of TDR, and high genetic diversity driven by the local expansion of different subtype B and F1 strains. These findings can contribute to the understanding about the dissemination and epidemiological and molecular characteristics of HIV-1 among the population of MSM living away from the epicenter of epidemics in Brazil.

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.

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 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations

2015 ◽  
Vol 43 (6) ◽  
pp. 3256-3271 ◽  
Author(s):  
Sushama Telwatte ◽  
Anna C. Hearps ◽  
Adam Johnson ◽  
Catherine F. Latham ◽  
Katie Moore ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Hiv 1

Evaluation of a novel in-house HIV-1 genotype drug resistance assay using clinical samples in China

2021 ◽  
Vol 19 ◽  
Author(s):  
Peijie Gao ◽  
Fengting Yu ◽  
Xiaozhen Yang ◽  
Dan Li ◽  
Yalun Shi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
High Efficiency ◽  
Clinical Samples ◽  
Genotype Distribution ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Subtype B ◽  
Hiv 1

Background: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic. Objective: The study aims to establish a novel in-house assay with high efficiency, named AP in-house method, that would be suitable for HIV-1 drug resistance detection in China. Methods: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system. Results : Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system. Conclusion: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversified HIV-1 subtypes in China.

scholarly journals Increase in HIV-1-transmitted drug resistance among ART-naïve youths at the China-Myanmar border during 2009 ~ 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yibo Ding ◽  
Min Chen ◽  
Jibao Wang ◽  
Yuecheng Yang ◽  
Yi Feng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Cd4 Count ◽  
Transmitted Drug Resistance ◽  
Subtype C ◽  
Reverse Transcriptase Inhibitors ◽  
Recombination Hotspots ◽  
Subtype B ◽  
Sex With Men ◽  
Hiv 1

Abstract Background HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. Methods From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. Results The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). Conclusions The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

scholarly journals Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in Beijing

2018 ◽  
Vol 146 (3) ◽  
pp. 339-344 ◽  
Author(s):  
Y.X. Song ◽  
R.L. Xin ◽  
Z.C. Li ◽  
H.W. Yu ◽  
W.H. Lun ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Frequent Mutations ◽  
Treatment Naïve ◽  
Sex With Men ◽  
Hiv 1

AbstractTo optimise patients’ outcomes and gain insight into transmitted drug resistance (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in Beijing, the prevalence of TDR was assessed. Demographic and clinical data of 1241 treatment-naive patients diagnosed between April 2014 and February 2015 were collected. TDR was defined using the Stanford University HIV drug resistance mutations database. The risk factors were evaluated by multi-logistic regression analysis. Among 932 successfully amplified cases, most were male (96.78%) and infected through men having sex with men (91.74%). Genotype were CRF01_AE (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%). The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of resistance, in which genotype C and other genotype may have higher risk for resistance. The prevalence among treatment-naive patients in Beijing was low. Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and prevent failures.

scholarly journals Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010–2018

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Tali Wagner ◽  
Neta S. Zuckerman ◽  
Tami Halperin ◽  
Daniel Chemtob ◽  
Itzchak Levy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Subtype C ◽  
Reverse Transcriptase Inhibitors ◽  
Subtype B ◽  
Hiv 1

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.

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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