Substantial Multiclass Transmitted Drug Resistance and Drug-Relevant Polymorphisms Among Treatment-Naïve Behaviorally HIV-Infected Youth

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

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Emerging transmitted drug resistance in treatment-naïve human immunodeficiency virus-1 CRF06_cpx-infected patients in Estonia

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365548.2010.526956 ◽

2010 ◽

Vol 43 (2) ◽

pp. 122-128 ◽

Cited By ~ 10

Author(s):

Radko Avi ◽

Kristi Huik ◽

Merit Pauskar ◽

Valentina Ustina ◽

Tonis Karki ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Transmitted Drug Resistance ◽

Immunodeficiency Virus ◽

Treatment Naïve ◽

Human Immunodeficiency Virus 1

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Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

Current HIV Research ◽

10.2174/1570162x19666211119111740 ◽

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.

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No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

Intervirology ◽

10.1159/000499367 ◽

2018 ◽

Vol 61 (6) ◽

pp. 281-291 ◽

Cited By ~ 2

Author(s):

Rongfeng Chen ◽

Bingyu Liang ◽

Binbin Wen ◽

Guanghua Huang ◽

Chuanyi Ning ◽

...

Keyword(s):

Drug Resistance ◽

Injection Drug Users ◽

Drug Users ◽

Antiretroviral Treatment ◽

Cross Sectional Study ◽

Injection Drug ◽

Transmitted Drug Resistance ◽

Sectional Study ◽

Cross Sectional ◽

Treatment Naïve

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2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2185 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S870-S870

Author(s):

Nina Theresa Dungca ◽

Brian Schwem ◽

Geraldine Arevalo ◽

Christian Francisco ◽

Christine Penalosa-Ramos ◽

...

Keyword(s):

Drug Resistance ◽

First Generation ◽

The Philippines ◽

Surveillance Study ◽

Transmitted Drug Resistance ◽

Strand Transfer ◽

Acquired Drug Resistance ◽

Nnrti Resistance ◽

Treatment Naïve ◽

Clinically Significant

Abstract Background Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. Methods We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. Results ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. Conclusion ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. Disclosures All authors: No reported disclosures.

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Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia

Scientific Reports ◽

10.1038/s41598-019-53520-8 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Maja Oroz ◽

Josip Begovac ◽

Ana Planinić ◽

Filip Rokić ◽

Maja M. Lunar ◽

...

Keyword(s):

Drug Resistance ◽

Single Case ◽

Clinical Care ◽

Resistance Testing ◽

Transmitted Drug Resistance ◽

Strand Transfer ◽

Primary Drug Resistance ◽

Treatment Naïve ◽

Pre Treatment ◽

Hiv 1

AbstractMolecular epidemiology of HIV-1 infection in treatment-naive HIV-1 infected persons from Croatia was investigated. We included 403 persons, representing 92.4% of all HIV-positive individuals entering clinical care in Croatia in 2014–2017. Overall prevalence of transmitted drug resistance (TDR) was estimated at 16.4%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTI (NNRTIs) and protease inhibitors (PIs) was found in 11.4%, 6.7% and 2.5% of persons, respectively. Triple-class resistance was determined in 2.2% of individuals. In addition, a single case (1.0%) of resistance to integrase strand-transfer inhibitors (InSTIs) was found. Deep sequencing was performed on 48 randomly selected samples and detected additional TDR mutations in 6 cases. Phylogenetic inference showed that 347/403 sequences (86.1%) were part of transmission clusters and identified forward transmission of resistance in Croatia, even that of triple-class resistance. The largest TDR cluster of 53 persons with T215S was estimated to originate in the year 1992. Our data show a continuing need for pre-treatment HIV resistance testing in Croatia. Even though a low prevalence of resistance to InSTI was observed, surveillance of TDR to InSTI should be continued.

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