Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.3
3.8
Journals
Viruses
Special Issues
Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer...
share announcement

Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 6158

Special Issue Editor

Prof. Dr. Bluma G. Brenner

E-Mail Website
Guest Editor
McGill AIDS Centre, McGill University, Montréal, QC, Canada
Interests: HIV-1 transmission; HIV drug resistance; HIV phylogenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are the mainstay of treatment and prevention measures for HIV/AIDS pandemic control. The expanded global access to ART has resulted in an exponential rise in acquired and transmitted HIV drug resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs), threatening the clinical benefits of ART in long-term HIV management. Recent ART and PrEP options have shifted to integrase strand transfer (INSTI)-based regimens that show higher potency and genetic barriers to resistance. The simplification to two-drug regimens and long-acting injectable formulations may result in a newly emergent resistance. This Special Issue welcomes articles that describe the potency, durability and pharmacokinetics of newer ART and PrEP options for virological suppression and as barriers to resistance.

Characterization of the genotypic, phenotypic, and phylogenetic features of emergent resistance species may provide a more nuanced understanding of the virologic potency and pharmacofragility of streamlined and long-acting regimens.

Prof. Dr. Bluma G. Brenner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HIV
  • antiretroviral therapy (ART)
  • pre-exposure prophylaxis (PrEP)
  • antiviral drugs
  • drug resistance

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Other

15 pages, 2294 KiB  
Article
Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries
by Alex Durand Nka, Yagai Bouba, Wilfried Rooker Tsapi Lontsi, Davy-Hyacinte Gouissi Anguechia, Georges Teto, Aude christelle Ka’e, Ezechiel Ngoufack Jagni Semengue, Collins Ambe Chenwi, Désiré Takou, Lum Forgwei, Tatiana Anim-Keng Tekoh, Aurelie Minelle Kengni Ngueko, Bernadette Bomgning Fokou, Jeremiah Efakika Gabisa, Michel Carlos Tommo Tchouaket, Willy Leroi TognaPabo, Derrick Tambe Ayuk Ngwese, Jacky Njiki Bikoi, Daniele Armenia, Vittorio Colizzi, Marcel Yotebieng, Nicaise Ndembi, Maria-Mercedes Santoro, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Alexis Ndjolo and Joseph Fokamadd Show full author list remove Hide full author list
Viruses 2025, 17(1), 69; https://doi.org/10.3390/v17010069 - 6 Jan 2025
Viewed by 1051
Abstract
Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL [...] Read more.
Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges. Full article
(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)
►▼ Show Figures

Figure 1

20 pages, 1862 KiB  
Article
Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 Subtype C Reverse Transcriptase to Islatravir
by Hyeonah Byun, Maria Antonia Papathanasopoulos, Kim Steegen and Adriaan Erasmus Basson
Viruses 2024, 16(12), 1888; https://doi.org/10.3390/v16121888 - 6 Dec 2024
Viewed by 1192
Abstract
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype [...] Read more.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL. Prevalent single and combinations of NRTI-resistant mutations were selected from a routine HIV-1 genotypic drug resistance testing database and introduced into HIV-1 subtype C-like pseudoviruses, which were then tested for ISL susceptibility. Single NRTI-resistant mutations were susceptible or showed only a low level of resistance to ISL. This included thymidine analogue mutations (TAMs, i.e., M41L, D67N, K70R, T215FY, and K219EQ) and non-TAMs (i.e., A62V, K65R, K70ET, L74IV, A114S, Y115F, and M184V). Combinations of M184V with one or more additional NRTI-resistant mutations generally displayed reduced ISL susceptibilities. This was more prominent for combinations that included M184V+TAMs, and particularly M184V+TAM-2 mutations. Combinations that included M184V+K65R did not impact significantly on ISL susceptibility. Our study suggests that ISL would be effective in treating people living with HIV (PLWH) failing tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) or TDF/emtricitabine (FTC)-containing regimens, but would be less effective in PLH failing zidovudine (AZT) with 3TC or FTC-containing regimens. Full article
(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)
►▼ Show Figures

Figure 1

14 pages, 2432 KiB  
Article
HIV Replication Under High-Level Cabotegravir Is Associated with the Appearance of 3′-PPT Mutations, Circular DNA Transcription and Recombination
by Xierong Wei, Jonathan T. Lipscomb, Ariana Santos Tino, Mian-er Cong, Susan Ruone, Meghan L. Bentz, Mili Sheth, Gerardo Garcia-Lerma and Jeffrey A. Johnson
Viruses 2024, 16(12), 1874; https://doi.org/10.3390/v16121874 - 30 Nov 2024
Viewed by 1136
Abstract
The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3′-polypurine tract (3′-PPT) adjacent to the 3′-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to [...] Read more.
The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3′-polypurine tract (3′-PPT) adjacent to the 3′-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB. HIV-1IIIB was cultured in paired experiments of continuous high (300 nM) CAB initiated 2 h or 24 h after infection. After eight months of CAB treatment, no int resistance was detected. Conversely, HIV RNA 3′-PPT mutants were detected within one month and were the majority virus by day 98. The appearance of 3′-PPT variants coincided with a rapid accumulation of HIV 1-LTR and 2-LTR circles. RNA amplification from the 3′-LTR TAR identified transcripts crossing 2-LTR circle junctions, which incorporated the adjacent U5 sequence identical to the 3′-PPT mutants. 3′-PPT variants were only identified in LTR circles and transcripts. Additionally, we found evidence of linear HIV and LTR circle recombination with human DNA at motifs homologous to 3′-PPT sequences. HIV persistence under CAB was associated with transcription and recombination of LTR circle sequences. Full article
(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)
►▼ Show Figures

Figure 1

17 pages, 3922 KiB  
Article
Frequency of Major Transmitted Integrase Resistance in Poland Remains Low Despite Change in Subtype Variability
by Kaja Mielczak, Karol Serwin, Anna Urbańska, Bogusz Aksak-Wąs, Malwina Karasińska-Cieślak, Elżbieta Mularska, Adam Witor, Paweł Jakubowski, Maria Hlebowicz, Monika Bociąga-Jasik, Elżbieta Jabłonowska, Aleksandra Szymczak, Bartosz Szetela, Władysław Łojewski and Miłosz Parczewski
Viruses 2024, 16(10), 1597; https://doi.org/10.3390/v16101597 - 11 Oct 2024
Viewed by 1040
Abstract
With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug [...] Read more.
With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation. Full article
(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)
►▼ Show Figures

Figure 1

13 pages, 1632 KiB  
Article
Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022
by Bluma G. Brenner, Ruxandra-Ilinca Ibanescu, Maureen Oliveira, Guillaume Margaillan, Bertrand Lebouché, Réjean Thomas, Jean Guy Baril, René-Pierre Lorgeoux, Michel Roger, Jean-Pierre Routy and the Montreal Primary HIV Infection (PHI) Cohort Study Group
Viruses 2024, 16(8), 1230; https://doi.org/10.3390/v16081230 - 31 Jul 2024
Viewed by 1137
Abstract
Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Methods: Time [...] Read more.
Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-naïve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2–5, vs. 6+ members per cluster as categorical variables. Results: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007–2011, 2012–2016, and 2017–2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14–73 IQR) and 16 (9–26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1–2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively (p < 0.0001). Conclusion: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR. Full article
(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)
►▼ Show Figures

Figure 1

Other

Jump to: Research

7 pages, 2305 KiB  
Brief Report
Investigation of Natural Resistance to Fostemsavir and Lenacapavir in Naïve Primary Infections by Ultra-Deep Sequencing of near Full-Length HIV-1 Genomes
by Elisabetta Lazzari, Gabriella Rozera, Roberta Gagliardini, Valentina Mazzotta, Lavinia Fabeni, Federica Forbici, Giulia Berno, Cristian Cosentino, Enrico Girardi, Andrea Antinori, Fabrizio Maggi and Isabella Abbate
Viruses 2025, 17(5), 636; https://doi.org/10.3390/v17050636 (registering DOI) - 28 Apr 2025
Viewed by 27
Abstract
Next-generation sequencing (NGS) of near full-length HIV genomes was performed to investigate natural resistance to Fostemsavir (FTR) and Lenacapavir (LEN) at the quasispecies level in nine naïve primary HIV infections harboring different HIV subtypes and recombinant forms. Reconstructed genomes provided a median (IQR) [...] Read more.
Next-generation sequencing (NGS) of near full-length HIV genomes was performed to investigate natural resistance to Fostemsavir (FTR) and Lenacapavir (LEN) at the quasispecies level in nine naïve primary HIV infections harboring different HIV subtypes and recombinant forms. Reconstructed genomes provided a median (IQR) coverage for gag and env of 1710 (750–6063) and 1768 (871–5270), respectively. In the gp120 encoding region, the M426R variant was found with a frequency of 100% in two HIV subtypes B: one of these also showed the A204T variant at 100%. In the more conserved capsid coding region no mutations possibly related to LEN natural resistance were observed. Full article
(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop