Trial reportJournal of virology2012
HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.
Trial report in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK-2048A Intravaginal Rings.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures.Journal of virology · 2012Trial
- Respiratory syncytial virus fuses with plasma membrane to infect primary cultures of bronchial epithelial cells.Frontiers in microbiology · 2025Article
- Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion.The Journal of biological chemistry · 2018Article
- Astrocytes Resist HIV-1 Fusion but Engulf Infected Macrophage Material.Cell reports · 2017Article
- Driving HIV-1 into a Vulnerable Corner by Taking Advantage of Viral Adaptation and Evolution.Frontiers in microbiology · 2017Review
- The β-Lactamase Assay: Harnessing a FRET Biosensor to Analyse Viral Fusion Mechanisms.Sensors (Basel, Switzerland) · 2016Review
- Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies.Antimicrobial agents and chemotherapy · 2016Article
- Characterizing the Diverse Mutational Pathways Associated with R5-Tropic Maraviroc Resistance: HIV-1 That Uses the Drug-Bound CCR5 Coreceptor.Journal of virology · 2015Article
- A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity.Retrovirology · 2015Article
- Maraviroc: a review of its use in HIV infection and beyond.Drug design, development and therapy · 2015Review
- Resistance to N-peptide fusion inhibitors correlates with thermodynamic stability of the gp41 six-helix bundle but not HIV entry kinetics.Retrovirology · 2014Article
- Genome-Wide Association Study of Human Immunodeficiency Virus (HIV)-1 Coreceptor Usage in Treatment-Naive Patients from An AIDS Clinical Trials Group Study.Open forum infectious diseases · 2014Article
- A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations.Retrovirology · 2013Article
- HIV-1 diversity in the envelope glycoproteins: implications for viral entry inhibition.Viruses · 2013Review
- Review
- Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance.Virology · 2012Article
- Article
- Differential use of CCR5 by HIV-1 clinical isolates resistant to small-molecule CCR5 antagonists.Antimicrobial agents and chemotherapy · 2012Article
- Controlling the HIV/AIDS epidemic: current status and global challenges.Frontiers in immunology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
HIV CCR5 antagonists select for env gene mutations that enable virus entry via drug-bound coreceptor. To investigate the mechanisms responsible for viral adaptation to drug-bound coreceptor-mediated entry, we studied viral isolates from three participants who developed CCR5 antagonist resistance during treatment with vicriviroc (VCV), an investigational small-molecule CCR5 antagonist. VCV-sensitive and -resistant viruses were isolated from one HIV subtype C- and two subtype B-infected participants; VCV-resistant isolates had mutations in the V3 loop of gp120 and were cross-resistant to TAK-779, an investigational antagonist, and maraviroc (MVC). All three resistant isolates contained a 306P mutation but had variable mutations elsewhere in the V3 stem. We used a virus-cell β-lactamase (BlaM) fusion assay to determine the entry kinetics of recombinant viruses that incorporated full-length VCV-sensitive and -resistant envelopes. VCV-resistant isolates exhibited delayed entry rates in the absence of drug, relative to pretherapy VCV-sensitive isolates. The addition of drug corrected these delays. These findings were generalizable across target cell types with a range of CD4 and CCR5 surface densities and were observed when either population-derived or clonal envelopes were used to construct recombinant viruses. V3 loop mutations alone were sufficient to restore virus entry in the presence of drug, and the accumulation of V3 mutations during VCV therapy led to progressively higher rates of viral entry. We propose that the restoration of pre-CCR5 antagonist therapy HIV entry kinetics drives the selection of V3 loop mutations and may represent a common mechanism that underlies the emergence of CCR5 antagonist resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.