High-level resistance to multiple drugs is often detected by directly sequencing uncloned polymerase chain reaction products (population-based sequencing). It is not known, however, if this method of identifying mutations gives an accurate picture of individual viral genomes. To determine how often multidrug-resistant isolates consist of clones containing every mutation present in the populatio...

Two large, independent human immunodeficiency virus type 1 resistance databases containing >7700 reverse-transcriptase (RT) sequences were used to analyze the epidemiology of amino acid substitutions at codons 44 and 118, which confer moderate lamivudine resistance in the presence of zidovudine resistance. As expected, E44A/D and V118I mutations were strongly associated with M41L, D67N, L210W, ...

There is a need for models useful for predicting the efficacy of agents developed for treating human immunodeficiency virus (HIV) based on information obtained during the drug development process. A pharmacodynamic model that superimposes the pharmacokinetics of anti-HIV nucleoside reverse transcription (RT) and protease inhibitors over a previously published predator-prey model of HIV and CD4 ...

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used in combination therapies against HIV-1. However, emergent and transmitted drug resistance compromise their efficacy the clinical setting. Y181C is selected patients receiving nevirapine, etravirine rilpivirine, together with K103N most prevalent NNRTI-associated mutation HIV-infected patients. Herein, we report on design, ...

We measured the effects of non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutations K101E+G190S, on replication fitness and EFV-resistance of HIV(NL4-3). K101E+G190S reduced fitness in the absence of EFV and increased EFV resistance, compared to either single mutant. Unexpectedly, K101E+G190S also replicated more efficiently in the presence of EFV than in its absence. Addition of...

A series of unnatural L-nucleosides such as 3TC, FTC and L-FMAU have been found to be potent antiviral agents. The mode of action of L-nucleosides has been found to be similar to that of D-nucleosides as antiviral agents, despite their unnatural stereochemistry, that is, nucleotide formation by kinases followed by interaction with the reverse transcriptase (RT) of HIV or DNA polymerase. To date...

Submit Manuscript | http://medcraveonline.com Abbreviations: PLHIV: People Living With HIV; HAART: Highly Active Antiretroviral Therapy; ART: Antiretroviral Therapy; ARV: Antiretroviral Drug; NNRTI: Non-Nucleoside ReverseTranscriptase Inhibitor; NRTI: Nucleoside Reverse-Transcriptase Inhibitor; PI: Protease Inhibitor; HIVDR: HIV Drug Resistance; PDR: Pretreatment HIV Drug Resistance; ADR: Acqui...

Despite the high degree of HIV-1 protease and reverse transcriptase (RT) mutation in the setting of antiretroviral therapy, the spectrum of possible virus variants appears to be limited by patterns of amino acid covariation. We analyzed patterns of amino acid covariation in protease and RT sequences from more than 7,000 persons infected with HIV-1 subtype B viruses obtained from the Stanford HI...

Submit Manuscript | http://medcraveonline.com Abbreviations: PLHIV: People Living With HIV; HAART: Highly Active Antiretroviral Therapy; ART: Antiretroviral Therapy; ARV: Antiretroviral Drug; NNRTI: Non-Nucleoside ReverseTranscriptase Inhibitor; NRTI: Nucleoside Reverse-Transcriptase Inhibitor; PI: Protease Inhibitor; HIVDR: HIV Drug Resistance; PDR: Pretreatment HIV Drug Resistance; ADR: Acqui...