ArticleAntimicrobial agents and chemotherapy2013
Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal: implications for second-line therapy.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2.The Journal of infectious diseases · 2020Pooled it
- Trial
- A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Longitudinal Analysis of HIV-2 Proviral DNA Reveals Archived Protease Inhibitor Resistance and Reservoir Evolution over Eight Years.International journal of molecular sciences · 2026Article
- Phenotypic impacts of treatment-selected mutations in HIV-2 protease on darunavir and lopinavir susceptibility: Evaluating genotypic HIV-2 drug resistance tools.PLOS global public health · 2026Article
- Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds.International journal of molecular sciences · 2023Review
- Article
- Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants.The Journal of infectious diseases · 2022Article
- Human Immunodeficiency Virus Type 2: The Neglected Threat.Pathogens (Basel, Switzerland) · 2021Review
- Long-term Experience and Outcomes of Programmatic Antiretroviral Therapy for Human Immunodeficiency Virus Type 2 Infection in Senegal, West Africa.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Observational
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- HIV-2 Drug Resistance Genotyping from Dried Blood Spots.Journal of clinical microbiology · 2020Article
- Impacts of drug resistance mutations on the structural asymmetry of the HIV-2 protease.BMC molecular and cell biology · 2020Article
- HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options.AIDS research and therapy · 2020Review
- Performance evaluation of a laboratory developed PCR test for quantitation of HIV-2 viral RNA.PloS one · 2020Article
- Article
- Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants.Antimicrobial agents and chemotherapy · 2019Article
- [HIV-2 infection in Senegal: virological failures and resistance to antiretroviral drugs (ARVs)].The Pan African medical journal · 2019Article
- Article
- Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Protease inhibitor (PI)-based antiretroviral therapy (ART) can effectively suppress HIV-2 plasma load and increase CD4 counts; however, not all PIs are equally active against HIV-2, and few data exist to support second-line therapy decisions. To identify therapeutic options for HIV-2 patients failing ART, we evaluated the frequency of PI resistance-associated amino acid changes in HIV-2 sequences from a cohort of 43 Senegalese individuals receiving unboosted indinavir (n = 18 subjects)-, lopinavir/ritonavir (n = 4)-, or indinavir and then lopinavir/ritonavir (n = 21)-containing ART. Common protease substitutions included V10I, V47A, I54M, V71I, I82F, I84V, L90M, and L99F, and most patients harbored viruses containing multiple changes. Based on genotypic data, we constructed a panel of 15 site-directed mutants of HIV-2ROD9 containing single- or multiple-treatment-associated amino acid changes in the protease-encoding region of pol. We then quantified the susceptibilities of the mutants to the HIV-2 "active" PIs saquinavir, lopinavir, and darunavir using a single-cycle assay. Relative to wild-type HIV-2, the V47A mutant was resistant to lopinavir (6.3-fold increase in the mean 50% effective concentration [EC50]), the I54M variant was resistant to darunavir and lopinavir (6.2- and 2.7-fold increases, respectively), and the L90M mutant was resistant to saquinavir (3.6-fold increase). In addition, the triple mutant that included I54M plus I84V plus L90M was resistant to all three PIs (31-, 10-, and 3.8-fold increases in the mean EC50 for darunavir, saquinavir, and lopinavir, respectively). Taken together, our data demonstrate that PI-treated HIV-2 patients frequently harbor viruses that exhibit complex patterns of PI cross-resistance. These findings suggest that sequential PI-based regimens for HIV-2 treatment may be ineffective.
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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.