scholarly journals Association of Virologic Failure and Nonnucleoside Reverse Transcriptase Inhibitor Resistance Found in Antiretroviral-Naive Children Infected With Human Immunodeficiency Virus and Given Efavirenz-Based Treatment

2019 ◽  
Vol 9 (2) ◽  
pp. 261-264
Author(s):  
Nikki Higa ◽  
Amy Pelz ◽  
Donald Birch ◽  
Ingrid A Beck ◽  
Tatiana Sils ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Nnrti Resistance ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Immunodeficiency Virus ◽  
Inhibitor Resistance ◽  
Reverse Transcriptase Inhibitor

Abstract Among 66 antiretroviral-naive children aged <3 years with human immunodeficiency virus (HIV) or coinfected with HIV and tuberculosis and initiating efavirenz-based antiretroviral therapy (ART), non–nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected before ART in 5 (7.6%). Virologic failure occurred in 2 of these children; they were last tested at 16 and 24 weeks of ART. Pre-ART NNRTI resistance was not associated with virologic failure.

scholarly journals Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor–Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Silvia Bertagnolio ◽  
Lucas Hermans ◽  
Michael R Jordan ◽  
Santiago Avila-Rios ◽  
Collins Iwuji ◽  
...  
Keyword(s):  
Systematic Review ◽  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Treatment Outcomes ◽  
Meta Analysis ◽  
Transcriptase Inhibitor ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor

Abstract Background Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). Methods We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). Results Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. Conclusions This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization’s recommendation to avoid using NNRTIs in countries where levels of PDR are high.

scholarly journals Anti-Human Immunodeficiency Virus Type 1 Activity of the Nonnucleoside Reverse Transcriptase Inhibitor GW678248 in Combination with Other Antiretrovirals against Clinical Isolate Viruses and In Vitro Selection for Resistance

2005 ◽  
Vol 49 (11) ◽  
pp. 4465-4473 ◽  
Author(s):  
Richard J. Hazen ◽  
Robert J. Harvey ◽  
Marty H. St. Clair ◽  
Robert G. Ferris ◽  
George A. Freeman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Amino Acid Substitutions ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Immunodeficiency Virus ◽  
Antiviral Activities ◽  
Approved Drugs ◽  
Reverse Transcriptase Inhibitor

ABSTRACT GW678248, a novel nonnucleoside reverse transcriptase inhibitor, has been evaluated for anti-human immunodeficiency virus activity in a variety of in vitro assays against laboratory strains and clinical isolates. When GW678248 was tested in combination with approved drugs in the nucleoside and nucleotide reverse transcriptase inhibitor classes or the protease inhibitor class, the antiviral activities were either synergistic or additive. When GW678248 was tested in combination with approved drugs in the nonnucleoside reverse transcriptase inhibitor class, the antiviral activities were either additive or slightly antagonistic. Clinical isolates from antiretroviral drug-experienced patients were selected for evaluation of sensitivity to GW678248 in a recombinant virus assay. Efavirenz (EFV) and nevirapine (NVP) had ≥10-fold increases in their 50% inhibitory concentrations (IC50s) for 85% and 98% of the 55 selected isolates, respectively, whereas GW678248 had a ≥10-fold increase in the IC50 for only 17% of these isolates. Thus, 81 to 83% of the EFV- and/or NVP-resistant viruses from this data set were susceptible to GW678248. Virus populations resistant to GW678248 were selected by in vitro dose-escalating serial passage. Resistant progeny viruses recovered after eight passages had amino acid substitutions V106I, E138K, and P236L in the reverse transcriptase-coding region in one passage series and amino acid substitutions K102E, V106A, and P236L in a second passage series.

scholarly journals Evaluation of inadequate anti-retroviral treatment in patients with HIV/AIDS

2012 ◽  
Vol 45 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Leonardo Carvalho da Fonseca ◽  
Francislene Juliana Martins ◽  
Rita de Cássia Padula Alves Vieira ◽  
Rouzeli Maria Coelho Pereira ◽  
Aline Siqueira Ferreira ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Patient Survival ◽  
Descriptive Study ◽  
Transcriptase Inhibitor ◽  
University Hospital ◽  
Reverse Transcriptase Inhibitors ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor

INTRODUCTION: Since the emergence of antiretroviral therapy, the survival of patients infected with human immunodeficiency virus has increased. Non-adherence to this therapy is directly related to treatment failure, which allows the emergence of resistant viral strains. METHODS: A retrospective descriptive study of the antiretroviral dispensing records of 229 patients from the Center for Health Care, University Hospital, Federal University of Juiz de Fora, Brazil, was conducted between January and December 2009. RESULTS: The study aimed to evaluate patient compliance and determine if there was an association between non-adherence and the therapy. Among these patients, 63.8% were men with an average age of 44.0 ± 9.9 years. The most used treatment was a combination of 2 nucleoside reverse transcriptase inhibitors with 1 non-nucleoside reverse transcriptase inhibitor (55.5%) or with 2 protease inhibitors (28.8%). It was found that patients taking lopinavir/ritonavir with zidovudine and lamivudine had a greater frequency of inadequate treatment than those taking atazanavir with zidovudine and lamivudine (85% and 83.3%, respectively). Moreover, when the combination of zidovudine/ lamivudine was used, the patients were less compliant (χ2 = 4.468, 1 degree of freedom, p = 0.035). CONCLUSIONS: The majority of patients failed to correctly adhere to their treatment; therefore, it is necessary to implement strategies that lead to improved compliance, thus ensuring therapeutic efficacy and increased patient survival.

scholarly journals In Vitro Microbicidal Activity of the Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) UC781 against NNRTI-Resistant Human Immunodeficiency Virus Type 1

2006 ◽  
Vol 80 (9) ◽  
pp. 4440-4446 ◽  
Author(s):  
Mohammad M. Hossain ◽  
Michael A. Parniak
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Resistant Virus ◽  
Microbicidal Activity ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

ABSTRACT The nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 is under development as a microbicide to prevent sexual transmission of the human immunodeficiency virus type 1 (HIV-1). However, NNRTI-resistant HIV-1 is increasingly prevalent in the infected population, and one of the concerns for NNRTI-based microbicides is that they will be ineffective against drug-resistant virus and may in fact selectively transmit NNRTI-resistant virus. We evaluated the microbicidal activity of UC781 against UC781-resistant (UCR), efavirenz-resistant (EFVR), and nevirapine-resistant (NVPR) strains in a variety of microbicide-relevant tests, including inactivation of cell-free virus, inhibition of cell-to-cell HIV-1 transmission, and the ability of UC781 pretreatment to protect cells from subsequent infection in the absence of exogenous drug. UC781 was 10- to 100-fold less effective against NNRTI-resistant HIV-1 compared to wild-type (wt) virus in each of these tests, with UC781 microbicidal activity against the various virus strains being wt ≥ NVPR > UCR ≥ EFVR. Breakthrough experiments using UC781-pretreated cells and mixtures of wt and NNRTI-resistant HIV-1 showed that UC781-pretreatment selected for NNRTI-resistant HIV-1. However, the efficacy of UC781 was dose dependent, and 25 μM UC781 provided essentially equivalent microbicidal activity against NNRTI-resistant and wt virus. The amount of UC781 in topical microbicide formulations under current development is approximately 100-fold greater than this concentration, so transmission of NNRTI-resistant virus may not be an issue at these microbicide formulation levels of UC781. Nonetheless, the reduced microbicidal activity of UC781 against NNRTI-resistant HIV-1 suggests that additional antiviral agents should be included in NNRTI-based microbicide formulations.

scholarly journals The K101P and K103R/V179D Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Resistance to Nonnucleoside Reverse Transcriptase Inhibitors

2006 ◽  
Vol 50 (1) ◽  
pp. 351-354 ◽  
Author(s):  
Neil T. Parkin ◽  
Soumi Gupta ◽  
Colombe Chappey ◽  
Christos J. Petropoulos
Keyword(s):  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Site Directed Mutagenesis ◽  
Resistance Mutations ◽  
Nnrti Resistance ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor

ABSTRACT Genotypic patterns associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in the absence of well-characterized resistance mutations were identified using a database (n > 47,000) of phenotype-genotype data. Among samples with no known NNRTI mutations, the most resistant samples contained K101P (n = 35) or a combination of K103R and V179D (n = 41). Site-directed mutagenesis confirmed the importance of these mutations.

Sign in / Sign up

Export Citation Format

Share Document