Advances in Research on HIV Drug Resistance and Other Determinants of Treatment Success: 3rd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 3788

Special Issue Editor


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Guest Editor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Malattie Infettive, 00168 Rome, Italy
Interests: HIV; antiretroviral therapy; dual therapy; simplification antiretroviral therapy; HIV drug resistance; HIV-DNA
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Special Issue Information

Dear Colleagues,

The field of antiretroviral therapy has been steadily evolving in recent years. New potent antiretroviral drugs have enabled the use of two-drug combinations for both naïve and treatment-experienced patients, alongside standard three-drug antiretroviral therapies. However, antiretroviral drug resistance and other viro-immunological factors (such as viral reservoir, viral subtypes, history of virological failure and therapeutic lines) can still play a role in influencing the risk of virological failure and therapy discontinuation. Moreover, since randomized trials typically exclude patients with those risk factors, clinicians involved in the HIV field have limited or no knowledge of how to safely optimize current antiretroviral therapies in a large proportion of patients with a long history of antiretroviral exposure (especially with previous virological failures), experiencing the burden of age-related, non-communicable diseases, toxicities from antiretroviral regimens and drug–drug interactions.

In addition to clinical trials, cohort studies from the clinical practice, as well as in vitro observations, are of paramount importance in characterizing the risk of virological failure with the newest treatment strategies. Since the advance of HIV medicine relies on personalized, rather than standardized, treatment strategies, research should still focus on the role of drug resistances and other predictors of treatment success, in order to reach the goal of a patient-centered therapeutic approach.

Dr. Alberto Borghetti
Guest Editor

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Keywords

  • HIV
  • antiretroviral therapies
  • virological failure
  • HIV drug resistance
  • HIV reservoir
  • HIV viral subtype
  • predictors of virological failure

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Published Papers (3 papers)

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Research

12 pages, 642 KB  
Article
Efficacy and Safety of Cabotegravir–Rilpivirine in PLWH: A Real-World Study
by Giuseppe Nicolò Conti, Serena Spampinato, Andrea De Vito, Andrea Marino, Teresa Cirelli, Viviana Coco, Alessia Mirabile, Rossella Fontana del Vecchio, Antonina Franco, Arturo Montineri, Chiara Fasca, Chiara Gullotta, Michele Salvatore Paternò Raddusa, Ylenia Russotto, Sonia Sofia, Grazia Pantò, Claudia Calì, Roberto Bruno, Eugenia Pistarà, Nunziatina Villari, Carmelo Iacobello, Bruno Cacopardo, Benedetto Maurizio Celesia, Giovanni F. Pellicanò, Francesco P. Antonucci, Sergio Lo Caputo, Giordano Madeddu, Giuseppe Nunnari and Emmanuele Venanzi Rulloadd Show full author list remove Hide full author list
Viruses 2025, 17(11), 1417; https://doi.org/10.3390/v17111417 - 24 Oct 2025
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Abstract
Background: Long-acting injectable antiretroviral therapy (LA-ART) with cabotegravir and rilpivirine (CAB + RPV) has emerged as a promising alternative to daily oral regimens for people living with HIV (PLWH), particularly those facing adherence challenges. While clinical trials have demonstrated its efficacy, real-world evidence [...] Read more.
Background: Long-acting injectable antiretroviral therapy (LA-ART) with cabotegravir and rilpivirine (CAB + RPV) has emerged as a promising alternative to daily oral regimens for people living with HIV (PLWH), particularly those facing adherence challenges. While clinical trials have demonstrated its efficacy, real-world evidence remains limited. Methods: This retrospective, multicenter study evaluated the efficacy and safety of CAB + RPV in 160 virologically suppressed PLWH across eight Italian infectious disease units. Participants received intramuscular CAB (600 mg) and RPV (900 mg) every eight weeks without an oral lead-in phase. Clinical, immunological, and biochemical parameters were assessed at baseline and after 24 weeks. Results: At week 24, 96.25% of participants maintained virological suppression, and the proportion of individuals with target-not-detected viral load increased from 71% to 76%. Only one case of virological failure was observed. Significant immunological improvements included an increase in the CD4+/CD8+ ratio (p = 0.0038) and a reduction in CD8+ T-cell count (p = 0.0150). Biochemical analysis showed a decrease in serum creatinine (p < 0.0001) and an increase in HDL cholesterol (p = 0.0223). Treatment discontinuation occurred in 3.75% of participants, primarily due to adverse events or psychological factors. Conclusions: CAB + RPV demonstrated high efficacy and tolerability in a real-world setting, with favorable immunological and metabolic outcomes. These findings support its use as a viable therapeutic option for PLWH, especially those with adherence barriers. Further long-term studies are warranted to confirm these results across broader populations. Full article
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16 pages, 250 KB  
Article
Behavioral Predictors of Intentional and Unintentional Nonadherence to Antiretroviral Therapy and Their Implications for Virological Failure Among People with HIV in Taiwan
by Su-Han Hsu, Chien-Chun Wang, Yung-Feng Yen, Tsen-Fang Yen, Po-Tsen Yeh and Hsin-Hao Lai
Viruses 2025, 17(10), 1375; https://doi.org/10.3390/v17101375 - 14 Oct 2025
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Abstract
Adherence to antiretroviral therapy (ART) is critical for HIV management and sustained virological suppression. Differentiating intentional from unintentional nonadherence is essential for developing tailored interventions, yet evidence from Asian populations remains limited. A cross-sectional study of 846 people with HIV (PWH) in northern [...] Read more.
Adherence to antiretroviral therapy (ART) is critical for HIV management and sustained virological suppression. Differentiating intentional from unintentional nonadherence is essential for developing tailored interventions, yet evidence from Asian populations remains limited. A cross-sectional study of 846 people with HIV (PWH) in northern Taiwan assessed ART adherence using the MARS-5 scale. Participants were categorized into good, unintentional, or intentional non-adherence groups. Logistic regression identified associated behavioral and psychosocial factors. Recreational drug use and younger age were independently linked to both unintentional and intentional poor adherence. Higher income and the use of single-tablet regimens were protective against intentional nonadherence, whereas disclosure of HIV status to a partner and an unsuppressed viral load were significantly associated with intentional nonadherence. Reported reasons included being too busy, emotional distress, and running out of medication. These findings suggest that intentional and unintentional nonadherence represent distinct behavioral patterns, with intentional lapses more strongly linked to virological failure. Addressing substance use, simplifying regimens, and providing psychosocial support after disclosure are essential to optimize adherence and achieve UNAIDS 2030 targets. Full article
19 pages, 1201 KB  
Article
Temporal Trends in HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in Istanbul, Türkiye (2021–2024): A Next-Generation Sequencing Study
by Murat Yaman, Begüm Saran Gülcen, Kübra Özgüler, Muammer Osman Köksal, Serap Demir Tekol and Arzu İlki
Viruses 2025, 17(4), 478; https://doi.org/10.3390/v17040478 - 27 Mar 2025
Cited by 1 | Viewed by 2298
Abstract
HIV-1 genotyping and drug resistance tests are routinely performed in virology laboratories in some countries, aiding clinical management. In Istanbul, between January 2021 and March 2024, plasma samples from 1029 HIV-1-infected patients were analyzed using the NGS method, and mutation and drug resistance [...] Read more.
HIV-1 genotyping and drug resistance tests are routinely performed in virology laboratories in some countries, aiding clinical management. In Istanbul, between January 2021 and March 2024, plasma samples from 1029 HIV-1-infected patients were analyzed using the NGS method, and mutation and drug resistance results were retrospectively evaluated alongside demographic data. Subtype B (54.4%) was most frequent in Turkish patients, while Subtype A1 (43.5%) was predominant among foreign nationals. The most common CRFs were CRF02_AG (3.8%) and CRF56_cpx (1.6%). According to the change in detection rates during the study period, Subtype B decreased, and Subtype A increased. The most frequent mutations detected were A62V (38.7%) and M184V (22.4%) for NRTIs; E138A (55.5%) and E138G (11.5%) for NNRTIs; M46I (33.3%) and M46L (25%) for PIs; and E92Q and G for INIs (total rate: 35.2%). Darunavir/ritonavir had the highest sensitivity rate, while resistance rates for NNRTIs and INIs increased over time. We anticipate that this study, in which we evaluate the routine use of an FDA-approved NGS kit alongside integrated bioinformatics data analysis and automated reporting software for the first time in Türkiye, will contribute to both national and international molecular epidemiological data and public health strategies by providing reliable results that align with international standarts. Full article
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