Development of a human immunodeficiency virus-1 in vitro DNA synthesis system to study reverse transcriptase inhibitors

1994 ◽  
Vol 23 (3-4) ◽  
pp. 235-249 ◽  
Author(s):  
Katyna Borroto-Esoda ◽  
Lawrence R. Boone
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Reverse Transcriptase Inhibitors ◽  
Synthesis System ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1

scholarly journals In Vitro Evaluation of Nonnucleoside Reverse Transcriptase Inhibitors UC-781 and TMC120-R147681 as Human Immunodeficiency Virus Microbicides

2004 ◽  
Vol 48 (1) ◽  
pp. 337-339 ◽  
Author(s):  
Yven Van Herrewege ◽  
Jo Michiels ◽  
Jens Van Roey ◽  
Katrien Fransen ◽  
Luc Kestens ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Sexual Transmission ◽  
Therapeutic Index ◽  
Reverse Transcriptase Inhibitors ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Immunodeficiency Virus

ABSTRACT The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission. Both drugs had a favorable therapeutic index. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV.

scholarly journals Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I

2019 ◽  
Vol 222 (7) ◽  
pp. 1108-1116 ◽  
Author(s):  
J Gregson ◽  
S Y Rhee ◽  
R Datir ◽  
D Pillay ◽  
C F Perno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Replication Capacity ◽  
Compensatory Mutation ◽  
First Line ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1

Abstract Background M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen. Methods We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro. Results M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05–.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus. Conclusions Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.

scholarly journals Anti-Human Immunodeficiency Virus Interactions of SCH-C (SCH 351125), a CCR5 Antagonist, with Other Antiretroviral Agents In Vitro

2002 ◽  
Vol 46 (5) ◽  
pp. 1336-1339 ◽  
Author(s):  
Cécile L. Tremblay ◽  
Françoise Giguel ◽  
Christopher Kollmann ◽  
Yongbiao Guan ◽  
Ting-Chao Chou ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
Reverse Transcriptase Inhibitors ◽  
Antiretroviral Agents ◽  
Synergistic Interactions ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.

scholarly journals Patterns of Resistance and Cross-Resistance to Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors in Patients Treated with the Nonnucleoside Reverse Transcriptase Inhibitor Loviride

1998 ◽  
Vol 42 (12) ◽  
pp. 3123-3129 ◽  
Author(s):  
Veronica Miller ◽  
Marie-Pierre de Béthune ◽  
Astrid Kober ◽  
Martin Stürmer ◽  
Kurt Hertogs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Cross Resistance ◽  
Reverse Transcriptase Inhibitors ◽  
Phenotypic Resistance ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) strains resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) may easily be selected for in vitro and in vivo under a suboptimal therapy regimen. Although cross-resistance is extensive within this class of compounds, newer NNRTIs were reported to retain activity against laboratory strains containing defined resistance-associated mutations. We have characterized HIV-1 resistance to loviride and the extent of cross-resistance to nevirapine, delavirdine, efavirenz, HBY-097, and tivirapine in a set of 24 clinical samples from patients treated with long-term loviride monotherapy by using a recombinant virus assay. Genotypic changes associated with resistance were analyzed by population sequencing. Overall, phenotypic resistance to loviride ranged from 0.04 to 3.47 log10-fold. Resistance was observed in samples from patients who had discontinued loviride for up to 27 months. Cross-resistance to the other compounds was extensive; however, fold resistance to efavirenz was significantly lower than fold resistance to nevirapine. No genotypic changes were detected in three samples; these were sensitive to all of the NNRTIs tested. The most common genotypic change was the K103N substitution. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTI.

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