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Biomedicines
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HIV Therapy: The Latest Developments in Antiviral Drugs
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HIV Therapy: The Latest Developments in Antiviral Drugs

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 8267

Editor

Dr. Francisco Javier Fanjul Losa

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Guest Editor
Infectious Diseases Unit, Hospital Universitario Son Espases, Palma de Mallorca, Spain
Interests: HIV; infectious diseases; COPD

Special Issue Information

Dear Colleagues,

This Special Issue, "HIV Therapy: The Latest Developments in Antiviral Drugs", aims to collate cutting-edge experimental and laboratory research on HIV treatments. Despite significant advancements in antiretroviral therapy (ART), challenges such as drug resistance, long-term toxicity, and the quest for a functional cure or eradication necessitate continuous innovation.

We invite contributions that delve into novel antiviral agents, including small molecules and biologics; their mechanisms of action; and innovative therapeutic strategies. Emphasis will be placed on preclinical studies, in vitro and ex vivo models, the virological and immunological mechanisms underlying new therapies, novel drug delivery systems explored at the laboratory level, and approaches to understanding and targeting HIV reservoirs.

This Special Issue will highlight basic and translational research that underpins the development of next-generation HIV therapies, focusing on the molecular, cellular, and immunological insights that will pave the way for future clinical applications. We welcome original research articles and comprehensive reviews that fit within this experimental medicine framework.

Dr. Francisco Javier Fanjul Losa
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines 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
  • antiviral drugs
  • experimental therapeutics
  • drug discovery
  • viral reservoirs
  • mechanism of action
  • preclinical models
  • novel HIV targets
  • antiretroviral therapy (ART)
  • immunotherapy (experimental aspects)

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Published Papers (3 papers)

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Research

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24 pages, 1461 KB  
Article
Methamphetamine Use in People Living with HIV: Clinical, Neurocognitive, and Blood Biomarker Profiles
by Monserrat Alvarez-Zavala, Nadia I. Álvarez-Álvarez, Jocelyn A. Cabrales-Lozano, Víctor Rodríguez-Pérez, José L. Ruíz-Sandoval, Andrea Torres-Rojas, Adriana Aguayo-Arelis, Tania E. Holguin-Aguirre, Luz A. González-Hernández, Jaime F. Andrade-Villanueva and Fernando Amador-Lara
Biomedicines 2026, 14(2), 443; https://doi.org/10.3390/biomedicines14020443 - 16 Feb 2026
Viewed by 1056
Abstract
Background: Methamphetamine (MA) use in people living with HIV (PLWH) has been linked to neurocognitive and behavioral dysregulation. We hypothesized that PLWH with active MA use (MAHIV) would show poorer cognitive performance, greater emotional and sleep burden, higher behavioral risk, and alterations in [...] Read more.
Background: Methamphetamine (MA) use in people living with HIV (PLWH) has been linked to neurocognitive and behavioral dysregulation. We hypothesized that PLWH with active MA use (MAHIV) would show poorer cognitive performance, greater emotional and sleep burden, higher behavioral risk, and alterations in circulating biomarkers of immune activation and neuronal injury, relative to PLWH without MA use and HIV-negative Controls. Methods: Cross-sectional analytic study of 121 adults: PLWH with MA use (MAHIV, n = 40), PLWH without use (n = 42), and HIV-negative Controls (n = 39). Outcomes were ART discontinuation, physical activity, neurocognition (MoCA), depression (BDI), anxiety (GAD-7), sleep (PSQI), and substance use (ASSIST). Circulating biomarkers measured by ELISA: sCD14, neuron-specific enolase (NSE), S100B, and neurofilament light chain (NfL). Results: MAHIV participants had more frequent ART discontinuation than PLWH and the lowest physical activity. Chemsex with polysubstance use, condomless sex, and multiple partners were most prevalent in MAHIV. This group showed the highest anxiety and depressive burdens, and the greatest sleep disturbances. Global cognition (MoCA) was lowest in MAHIV, with significant deficits in executive function, memory, attention, and language; 82.5% had at least mild cognitive impairment. sCD14 was significantly higher in MAHIV than in PLWH and Controls, and NSE was elevated in both MAHIV and PLWH versus Controls. sCD14 correlated inversely with MoCA and positively with GAD-7 and BDI-II. Conclusions: Among PLWH, MA use is associated with greater ART nonadherence, syndemic mental-health and sleep disturbances, broader neurocognitive deficits, and elevations in circulating sCD14 and NSE. The sCD14–cognition and sCD14–mood relationships highlight chronic immune activation as a candidate pathway for neurocognitive and affective impairment and support sCD14 and NSE as potential stratification and monitoring biomarkers in MA-using PLWH. Full article
(This article belongs to the Special Issue HIV Therapy: The Latest Developments in Antiviral Drugs)
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Review

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19 pages, 756 KB  
Review
Next-Generation HIV-1 Therapeutics in Co-Endemic Settings
by Brandon Ngo and Richard E. Sutton
Biomedicines 2026, 14(2), 330; https://doi.org/10.3390/biomedicines14020330 - 31 Jan 2026
Viewed by 1567
Abstract
The development of next-generation HIV-1 therapeutics, including ultralong-acting antivirals, novel mechanistic classes, and curative immunotherapies, promises to overcome the limitations of lifelong, daily antiretroviral therapy (ART). However, the real-world efficacy of these treatments depends on the complex epidemiological landscapes in which they are [...] Read more.
The development of next-generation HIV-1 therapeutics, including ultralong-acting antivirals, novel mechanistic classes, and curative immunotherapies, promises to overcome the limitations of lifelong, daily antiretroviral therapy (ART). However, the real-world efficacy of these treatments depends on the complex epidemiological landscapes in which they are used. In South America, HIV-1 epidemics intersect hyperendemic arboviruses, including dengue, Zika, chikungunya, and yellow fever, and regionally isolated pathogens, such as mammarenaviruses. These co-infections cause profound episodic immune activation and organ dysfunction that alter drug pharmacokinetics, disrupting healthcare access and adherence. These factors can compromise ART efficacy, promote resistance, and influence latent reservoir dynamics. This review synthesizes clinical and translational evidence of this intersection. We evaluate how emergent agents, such as capsid inhibitors (lenacapavir), long-acting injectables (cabotegravir/rilpivirine), maturation inhibitors (GSK3640254), and broadly neutralizing antibodies (bNAbs), perform in the context of co-endemic viral challenges. Specifically, we argue that therapeutic development must become “co-infection-aware” to progress toward a cure and achieve durable HIV-1 control. We provide a translational roadmap that explicitly incorporates co-infection endpoints into clinical trials, develops preclinical models that better reflect real-world viral exposures, and prioritizes implementation strategies that remain effective in the case of recurrent outbreaks. Integrating regional viral ecology into HIV-1 therapeutic research is therefore a necessary step toward developing interventions that are durable and effective on a global scale. Full article
(This article belongs to the Special Issue HIV Therapy: The Latest Developments in Antiviral Drugs)
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11 pages, 604 KB  
Review
HIV Therapy: The Latest Developments in Antiviral Drugs—A Scoping Review
by Francisco Fanjul, Meritxell Gavalda, Antoni Campins, Adria Ferré, Luisa Martín, María Peñaranda, Mari Ángeles Ribas, Elena Pastor-Ramon, Sophia Pinecki and Melchor Riera
Biomedicines 2025, 13(11), 2629; https://doi.org/10.3390/biomedicines13112629 - 27 Oct 2025
Viewed by 5200
Abstract
Background: Major advances in antiretroviral therapy (ART) have transformed HIV into a chronic condition, yet drug resistance, long-term toxicities, adherence challenges, and persistent viral reservoirs continue to drive innovation. Objectives: To map and synthesize recent developments in anti-HIV drugs and delivery platforms with [...] Read more.
Background: Major advances in antiretroviral therapy (ART) have transformed HIV into a chronic condition, yet drug resistance, long-term toxicities, adherence challenges, and persistent viral reservoirs continue to drive innovation. Objectives: To map and synthesize recent developments in anti-HIV drugs and delivery platforms with a focus on (i) new molecules in clinical development and (ii) novel mechanisms of action, following a scoping review framework aligned with PRISMA-ScR. Sources: We interrogated PubMed, Embase.com, Web of Science, and Scopus (January 2020–September 2025) and screened abstracts from CROI, IAS/AIDS, IDWeek, and HIV Glasgow (2023–2025). Content: The evidence base underscores capsid inhibition (lenacapavir) for multidrug-resistant HIV and its expansion into prevention, long-acting intramuscular maintenance with cabotegravir/rilpivirine, maturation inhibitors (zabofiravir), and attachment inhibition with fostemsavir. Broadly neutralizing antibodies (bNAbs) can sustain ART-free suppression in selected individuals. Ultra-long-acting delivery systems are advancing toward translational evaluation. Summary: The pipeline is diversifying toward less frequent dosing, new targets, and combination strategies. Successful and ethical implementation will require resistance-informed selection, equitable access, and reimagined healthcare delivery models that accommodate long-acting technologies. Full article
(This article belongs to the Special Issue HIV Therapy: The Latest Developments in Antiviral Drugs)
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