scholarly journals Near Real-Time Identification of Recent Human Immunodeficiency Virus Transmissions, Transmitted Drug Resistance Mutations, and Transmission Networks by Multiplexed Primer ID–Next-Generation Sequencing in North Carolina

Author(s):  
Shuntai Zhou ◽  
Sabrina Sizemore ◽  
Matt Moeser ◽  
Scott Zimmerman ◽  
Erika Samoff ◽  
...  

Abstract Background The identification of recent human immunodeficiency virus (HIV) 1 infections among people with new HIV diagnoses is important to both tailoring and assessing the impact of HIV-1 prevention strategies. Methods We developed a multiplexed Primer ID–next-generation sequencing approach to identify recent infections by measuring the intrahost viral diversity over multiple regions of the HIV-1 genome, in addition to detecting drug resistance mutations (DRMs) and phylogenetically linked clusters. We summarize the field implementation of this all-in-one platform among persons with newly diagnosed HIV-1 by the North Carolina State Laboratory of Public Health in 2018. Results Overall, recent infection was identified in 94 (35%) of 268 patients with new HIV diagnoses. People <30 years old, and people who inject drugs were more likely to have diagnoses of recent infection. The reverse-transcriptase region K103N was the most commonly detected DRM (prevalence, approximately 15%). We found a total of 28 clusters, and persons with recent infection were more likely to be cluster members than were those with chronic infections (P = .03). Conclusions We demonstrate the rapid identification of recent infection and pretreatment DRMs coupled with cluster analysis that will allow prioritization of linkage to care, treatment, and prevention interventions to those at highest risk of onward transmission.

2020 ◽  
Vol 221 (12) ◽  
pp. 1962-1972 ◽  
Author(s):  
Philip L Tzou ◽  
Diane Descamps ◽  
Soo-Yon Rhee ◽  
Dana N Raugi ◽  
Charlotte Charpentier ◽  
...  

Abstract Background HIV-1 and HIV-2 differ in their antiretroviral (ARV) susceptibilities and drug resistance mutations (DRMs). Methods We analyzed published HIV-2 pol sequences to identify HIV-2 treatment-selected mutations (TSMs). Mutation prevalences were determined by HIV-2 group and ARV status. Nonpolymorphic mutations were those in <1% of ARV-naive persons. TSMs were those associated with ARV therapy after multiple comparisons adjustment. Results We analyzed protease (PR) sequences from 483 PR inhibitor (PI)-naive and 232 PI-treated persons; RT sequences from 333 nucleoside RT inhibitor (NRTI)-naive and 252 NRTI-treated persons; and integrase (IN) sequences from 236 IN inhibitor (INSTI)-naive and 60 INSTI-treated persons. In PR, 12 nonpolymorphic TSMs occurred in ≥11 persons: V33I, K45R, V47A, I50V, I54M, T56V, V62A, A73G, I82F, I84V, F85L, L90M. In RT, 9 nonpolymorphic TSMs occurred in ≥10 persons: K40R, A62V, K70R, Y115F, Q151M, M184VI, S215Y. In IN, 11 nonpolymorphic TSMs occurred in ≥4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, R231 5-amino acid insertions. Nine of 32 nonpolymorphic TSMs were previously unreported. Conclusions This meta-analysis confirmed the ARV association of previously reported HIV-2 DRMs and identified novel TSMs. Genotypic and phenotypic studies of HIV-2 TSMs will improve approaches to predicting HIV-2 ARV susceptibility and treating HIV-2–infected persons.


PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0211587
Author(s):  
Géraldine Dessilly ◽  
Léonie Goeminne ◽  
Anne-thérèse Vandenbroucke ◽  
François E. Dufrasne ◽  
Anandi Martin ◽  
...  

2021 ◽  
Vol 1 (1) ◽  
pp. 113-123
Author(s):  
Ahmad A. Hachem ◽  
Essa H. Hariri ◽  
Anthony Mansour ◽  
Jacques Mokhbat

Background: Antiretroviral drug resistance remains a significant problem in the clinical management of patients infected with the Human Immunodeficiency Virus type-1. Aim: This study investigates and reports data on the molecular characterization of HIV-1 isolates from patients who are in a state of therapy failure. Methods: This is a retrospective study conducted on 65 patients in therapy failure. Inclusion criteria included patients diagnosed as being in therapy failure between the years 2009 and 2013. We defined ART failure as either a failure to achieve viral suppression or a failure to detect viral loads below 500 copies/mL after virological suppression in at least two plasma samples.  We used the published WHO list for surveillance of transmitted resistance and the Stanford HIV Drug Resistance Database to identify drug resistance mutations. Results: 65% of the participants had at least one drug resistance mutation (DRM). 12% of the population sampled had resistance to only one ART class, 32% presented with resistance to two classes of antiretroviral drugs, and 20% had resistance to all three classes of drugs. The prevalence of nucleoside transcriptase inhibitor (NRTI) mutations was 55%, the most common DRM being M184V. The prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations was 58%, with the most common mutation being the K103N mutation. The prevalence of protease inhibitors drug resistance mutations was 23%, with mutations V82A and I47V being present in 10% of the study population. Conclusion: Our study is the first molecular characterization of DRM emergence in HIV-1 strains from patients failing antiretroviral therapy in Lebanon. Continuous monitoring of resistance patterns for HIV in the country is necessary to tackle the emergent drug resistance.


2002 ◽  
Vol 76 (18) ◽  
pp. 9253-9259 ◽  
Author(s):  
Louis M. Mansky ◽  
Dennis K. Pearl ◽  
Lisa C. Gajary

ABSTRACT Replication of drug-resistant human immunodeficiency virus type 1 (HIV-1) in the presence of drug can lead to the failure of antiretroviral drug treatment. Drug failure is associated with the accumulation of drug resistance mutations. Previous studies have shown that 3′-azido-3′-deoxythymidine (AZT), (−)2′,3′-dideoxy-3′-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT) can increase the virus in vivo mutation rate. In this study, the combined effects of drug-resistant RT and antiretroviral drugs on the HIV-1 mutant frequency were determined. In most cases, a multiplicative effect was observed with AZT-resistant or AZT/3TC dually resistant RT and several drugs (i.e., AZT, 3TC, hydroxyurea, and thymidine) and led to increases in the odds of recovering virus mutants to over 20 times that of the HIV-1 mutant frequency in the absence of drug or drug-resistance mutations. This observation indicates that HIV-1 can mutate at a significantly higher rate when drug-resistant virus replicates in the presence of drug. These increased mutant frequencies could have important implications for HIV-1 population dynamics and drug therapy regimens.


Medicine ◽  
2019 ◽  
Vol 98 (6) ◽  
pp. e14313 ◽  
Author(s):  
Christopher Z. Abana ◽  
Kwamena W.C. Sagoe ◽  
Evelyn Y. Bonney ◽  
Edward K. Maina ◽  
Ishmael D. Aziati ◽  
...  

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