scholarly journals Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population

2018 ◽  
Vol 68 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Dana Clutter ◽  
W Jeffrey Fessel ◽  
Daniel Klein ◽  
Sally Slome ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Molecular Epidemiology ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Genetic Mechanisms ◽  
Clinic Population

scholarly journals Pretreatment human immunodeficiency virus type 1 (HIV-1) drug resistance in transmission clusters of the Cologne-Bonn region, Germany

2019 ◽  
Vol 25 (2) ◽  
pp. 253.e1-253.e4 ◽  
Author(s):  
M. Stecher ◽  
A. Chaillon ◽  
A.M. Eis-Hübinger ◽  
C. Lehmann ◽  
G. Fätkenheuer ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Nucleotide and Amino Acid Polymorphisms at Drug Resistance Sites in Non-B-Subtype Variants of Human Immunodeficiency Virus Type 1

2004 ◽  
Vol 48 (8) ◽  
pp. 2993-2998 ◽  
Author(s):  
Dan Turner ◽  
Bluma Brenner ◽  
Daniela Moisi ◽  
Mervi Detorio ◽  
Raymond Cesaire ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Subtype A ◽  
Silent Substitutions

ABSTRACT We have compared nucleotide substitutions and polymorphisms at codons known to confer drug resistance in subtype B strains of human immunodeficiency virus type 1 (HIV-1) with similar substitutions in viruses of other subtypes. Genotypic analysis was performed on viruses from untreated individuals. Nucleotide and amino acid diversity at resistance sites was compared with a consensus subtype B reference virus. Among patients with non-subtype B infections, polymorphisms relative to subtype B were observed at codon 10 in protease (PR). These included silent substitutions (CTC→CTT, CTA, TTA) and an amino acid mutation, L10I. Subtype A viruses possessed a V179I substitution in reverse transcriptase (RT). Subtype G viruses were identified by silent substitutions at codon 181 in RT (TAT→TAC). Similarly, subtype A/G viruses were identified by a substitution at position 67 in RT (GAC→GAT). Subtype C was distinguished by silent substitutions at codons 106 (GTA→GTG) and 219 (AAA→AAG) in RT and codon 48 (GGG→GGA) in PR. Variations relative to subtype B were seen at RT position 215 (ACC→ACT) for subtypes A and A/E. These substitutions and polymorphisms reflect different patterns of codon usage among viruses of different subtypes. However, the existence of different subtypes may only rarely affect patterns of drug resistance-associated mutations.

scholarly journals Sensitivity to a Nonpeptidic Compound (RPR103611) Blocking Human Immunodeficiency Virus Type 1 Env-Mediated Fusion Depends on Sequence and Accessibility of the gp41 Loop Region

2000 ◽  
Vol 74 (5) ◽  
pp. 2142-2150 ◽  
Author(s):  
Béatrice Labrosse ◽  
Carole Treboute ◽  
Marc Alizon
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Conformational Changes ◽  
Loop Region ◽  
Immunodeficiency Virus ◽  
The Stability ◽  
Hiv 1

ABSTRACT The triterpene RPR103611 is an efficient inhibitor of membrane fusion mediated by the envelope proteins (Env, gp120-gp41) of CXCR4-dependent (X4) human immunodeficiency virus type 1 (HIV-1) strains, such as HIV-1LAI (LAI). Other X4 strains, such as HIV-1NDK (NDK), and CCR5-dependent (R5) HIV-1 strains, such as HIV-1ADA (ADA), were totally resistant to RPR103611. Analysis of chimeric LAI-NDK Env proteins identified a fragment of the NDK gp41 ectodomain determining drug resistance. A single difference at position 91, leucine in LAI and histidine in NDK, apparently accounted for their sensitivity or resistance to RPR103611. We had previously identified a mutation of isoleucine 84 to serine in a drug escape LAI variant. Both I84 and L91 are located in the “loop region” of gp41 separating the proximal and distal helix domains. Nonpolar residues in this region therefore appear to be important for the antiviral activity of RPR103611 and are possibly part of its target. However, another mechanism had to be envisaged to explain the drug resistance of ADA, since its gp41 loop region was almost identical to that of LAI. Fusion mediated by chimeric Env consisting of LAI gp120 and ADA gp41, or the reciprocal construct, was fully blocked by RPR103611. The gp120-gp41 complex of R5 strains is stable, relative to that of X4 strains, and this stability could play a role in their drug resistance. Indeed, when the postbinding steps of ADA infection were performed under mildly acidic conditions (pH 6.5 or 6.0), a treatment expected to favor dissociation of gp120, we achieved almost complete neutralization by RPR103611. The drug resistance of NDK was partially overcome by preincubating virus with soluble CD4, a gp120 ligand inducing conformational changes in the Env complex. The antiviral efficacy of RPR103611 therefore depends on the sequence of the gp41 loop and the stability of the gp120-gp41 complex, which could limit the accessibility of this target.

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