scholarly journals Statewide Longitudinal Trends in Transmitted HIV-1 Drug Resistance in Rhode Island, USA

Author(s):  
Vlad Novitsky ◽  
Jon Steingrimsson ◽  
Fizza S Gillani ◽  
Mark Howison ◽  
Su Aung ◽  
...  

Abstract Background HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island. Methods Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase and integrase sequences, routinely obtained over 2004–2020. TDR extent, trends, impact on 1 st-line regimens, and association with transmission networks were assessed using Stanford Database, Mann-Kendall statistic, and phylogenetic tools. Results In 1,123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by NNRTI (5-18%), and less NRTI TDR (2-8%). Dual- and triple-class TDR were low and major InSTI resistance was absent. Predicted intermediate-high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters. Conclusions In a unique (statewide) assessment over 2004–2020, TDR increased, primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multi-class regimens and PrEP are encouraging, however, surveillance and its integration with molecular epidemiology should continue, to potentially improve care and prevention interventions.

2020 ◽  
Vol 17 (6) ◽  
pp. 397-407
Author(s):  
Maryam Jarchi ◽  
Farah Bokharaei-Salim ◽  
Maryam Esghaei ◽  
Seyed Jalal Kiani ◽  
Fatemeh Jahanbakhsh ◽  
...  

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.


2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maja Oroz ◽  
Josip Begovac ◽  
Ana Planinić ◽  
Filip Rokić ◽  
Maja M. Lunar ◽  
...  

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.


2017 ◽  
Vol 163 (1) ◽  
pp. 297-297
Author(s):  
Shokouh Ghafari ◽  
Arash Memarnejadian ◽  
Alireza Samarbaf-zadeh ◽  
Ehsan Mostafavi ◽  
Manoochehr Makvandi ◽  
...  

2015 ◽  
Vol 70 ◽  
pp. S115
Author(s):  
Mert Ahmet Kuskucu ◽  
Kenan Midilli ◽  
Mucahit Yemisen ◽  
Ali Abdelkareem ◽  
Sevgi Ergin ◽  
...  

2021 ◽  
Vol 9 ◽  
Author(s):  
Dan Yuan ◽  
Bin Yu ◽  
Yiping Li ◽  
Zixin Wang ◽  
Meijing Liu ◽  
...  

Introduction: Transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) efficacy. We aimed to understand the molecular epidemiology of TDR and its genetic transmission networks among newly diagnosed people living with HIV/AIDS (PLWH).Methods: A total of 1,318 newly diagnosed PLWH, identified in all population-based HIV screening in an HIV-affected county of a minority area of China (i.e., Butuo county), were enrolled between January 1, 2018, and November 31, 2018. HIV-1 pol gene sequences were used for phylogenetic and genotypic drug resistance analyses. The genetic transmission networks were identified.Results: The prevalence of TDR among newly diagnosed PLWH was 8.12% (107/1,318). Patients in the stage of AIDS (adjusted odds ratio, OR: 2.32) and who had a history of sharing a needle ≥5 times (adjusted OR: 3.89) were more likely to have an increased risk of TDR. The prevalence of TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) is higher than that of other inhibitors, with a relatively high prevalence of three mutations [V179D/E/DE (4.93%), K103N/KN (3.11%), and E138A/G (1.52%)]. A total of 577 (43.78%) pol sequences were involved in the genetic transmission network, with 171 clusters ranging in size from 2 to 91 pol sequences; 37.38% (40/107) of individuals carrying TDR were involved in the network, and individuals with the same TDR-associated mutations were usually cross-linked.Conclusions: Our data suggest a relatively high level of TDR and many transmission clusters among the newly diagnosed PLWH. Targeted intervention, early identification, and monitoring of resistance are warranted to reduce the TDR and prevent HIV-1 transmission in areas with a high rate of HIV-1.


PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0206177 ◽  
Author(s):  
Amin S. Hassan ◽  
Joakim Esbjörnsson ◽  
Elizabeth Wahome ◽  
Alexander Thiong’o ◽  
George N. Makau ◽  
...  

Sexual Health ◽  
2020 ◽  
Vol 17 (4) ◽  
pp. 377
Author(s):  
Daniel Richardson ◽  
Hubert Chan ◽  
Rohan Bopage ◽  
David A. Lewis ◽  
Shailendra Sawleshwarkar ◽  
...  

Abstract Background Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) is an important contributor to antiretroviral treatment failure, and is associated with HIV-1 transmission among men who have sex with men (MSM), non-MSM clusters and individuals diagnosed with concurrent sexually transmissible infections (STI). Western Sydney has a culturally diverse population, with a high proportion of non-Australian-born individuals. This study describes the prevalence of TDR and non-B HIV-1 subtypes in a clinic-based population. Methods: A clinic database was examined for all newly diagnosed treatment-naïve HIV-1 patients and information on their HIV-1 resistance and subtype, demographics including country of birth and diagnosis of a bacterial sexually transmissible infection was collected. Results: Data were available from 74/79 individuals (62 cis-male, 16 cis-female and 1 transgender woman). Of the 74 genotypes, the prevalence of non-B subtypes and TDR was 43/74 (58%; 95%CI = 46.9–69.3) and 14/74 (19%; 95%CI = 10.0 to 27.8). It was also found that 30/79 (38%) had a concurrent bacterial STI. TDR was associated with subtype B infection (OR 3.53; 95%CI = 1.41–8.82; P = 0.007) and being born in Australia (OR 12.0; 95%CI = 2.45–58.86; P = 0.002). Conclusion: The relative prevalence of non-B HIV-1 subtypes and TDR is higher in Western Sydney than in the rest of Australia. TDR is associated with subtype B HIV-1 and being Australian born, suggesting ongoing local transmission. This highlights the diversity of the HIV epidemic locally and the need for interventions to prevent ongoing HIV transmission.


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