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Advances in Molecular Therapeutics for HIV Co-Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 March 2026 | Viewed by 2252

Special Issue Editors

Special Issue Information

Dear Colleagues,

Ever since human immunodeficiency virus (HIV) was first discovered in 1981 more than 40 million people have died due to acquired immunodeficiency syndrome (AIDS). Currently 38 million people are living with HIV infection. HIV compromises the body’s immune system, increasing the likelihood of contracting opportunistic infections.

AIDS patients often suffer or die due to tuberculosis (TB). HIV and TB are considered a syndemic, defined as “the convergence of two or more diseases that act synergistically to magnify the burden of disease”. Today, TB remains the leading infectious cause of death in people with HIV, who are 15–22 times more likely to contract TB than people without. Importantly, HIV has been linked to several outbreaks of TB globally, especially in sub-Saharan Africa.

Much is known about the syndemic relationship of HIV and TB, yet the specifics and mechanisms behind how these two diseases interact have not been entirely addressed. This review will explore how Mtb worsens HIV infection. The objective of this review is to provide an insight into the interaction between Mtb and HIV to help overcome the difficulties in co-treatment of HIV and TB.

The special issue therefore invites submissions on:

  • Strategies to maintain the immune system in those with HIV infection tp prevent M. tb co-infection.
  • Adjunctive therapies for HIV and M. tb co-infection.
  • Novel therapies to prevent HIV infection and M. tb co-infection in HIV-infected individuals.
  • Treatment that will maintain undetectable viral load to prevent co-infections with tuberculous and non-tuberculous mycobacterial infections.
  • Efforts to prevent HIV from developing resistance to ART.
  • Recent developments in understanding the host immune responses against HIV and M. tb/M. avium co-infections.
  • Current breakthroughs in the understanding of M. tb pathogenesis in the context of HIV infection.

Prof. Dr. Vishwanath Venketaraman
Dr. Selvakumar Subbian
Guest Editors

Manuscript Submission Information

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Keywords

  • HIV co-infections
  • molecular therapeutics
  • Mtb
  • ART
  • immune responses

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Published Papers (2 papers)

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Research

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22 pages, 2220 KB  
Article
A First-in-Class Dual Degrader of Bcl-2/Bcl-xL Reverses HIV Latency and Minimizes Ex Vivo Reservoirs from Patients
by Lin-Chun Chang, Michael T. Yin, Gregory M. Laird, Kristen D. Ritter, Jayesh G. Shah and Asim K. Debnath
Int. J. Mol. Sci. 2025, 26(6), 2772; https://doi.org/10.3390/ijms26062772 - 19 Mar 2025
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Abstract
The persistence of latent HIV-1 proviruses in CD4+ T cells is a major obstacle to curing HIV. The “shock and kill” strategy involves reversing latency with latency-reversing agents (LRAs) and selectively inducing cell death in infected cells. However, current LRAs have shown [...] Read more.
The persistence of latent HIV-1 proviruses in CD4+ T cells is a major obstacle to curing HIV. The “shock and kill” strategy involves reversing latency with latency-reversing agents (LRAs) and selectively inducing cell death in infected cells. However, current LRAs have shown limited efficacy in eliminating the ex vivo HIV reservoir and thus failed in clinical study. In this study, we repurposed PZ703b, a pro-apoptotic protein degrader initially developed for anti-leukemia therapy, to target HIV eradication. PZ703b induced the degradation of Bcl-2 and Bcl-xL, activating the non-canonical NF-kB pathway and caspases cascade, resulting in latency reversal and the selective apoptosis of infected cells. The treatment of ex vivo CD4+ T cells from ART-suppressed HIV-1 patients led to approximately a 50% reduction in the replication-competent reservoir. While this result does not reach the threshold required for a complete cure, it demonstrates the potential of a dual degrader of Bcl-2/Bcl-xL in reversing HIV latency and inducing selective cell death. Our study provides a proof-of-concept for using dual degraders of Bcl-2/Bcl-xL as a novel category of LRAs in therapeutic strategies aimed at reducing HIV reservoirs. This approach may pave the way for the further exploration of targeted interventions to eliminate the HIV-inducible reservoir. Full article
(This article belongs to the Special Issue Advances in Molecular Therapeutics for HIV Co-Infections)
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Review

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31 pages, 1480 KB  
Review
Overcoming Treatment Challenges in HIV-Associated Mycobacterial Diseases: New Therapeutic Frontiers
by Omid Nikjeh, Seyedehparmis Rejali, Kayvan Sasaninia and Vishwanath Venketaraman
Int. J. Mol. Sci. 2025, 26(21), 10325; https://doi.org/10.3390/ijms262110325 - 23 Oct 2025
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Abstract
For drug-susceptible TB, the WHO-endorsed first-line regimen (isoniazid, rifampicin, ethambutol, pyrazinamide) remains the global reference. Therapy must always be tailored to drug susceptibility, especially in MDR- and XDR-TB. HIV-associated mycobacterial infections—including Mycobacterium tuberculosis (TB), disseminated Mycobacterium avium complex (MAC), and Mycobacterium leprae ( [...] Read more.
For drug-susceptible TB, the WHO-endorsed first-line regimen (isoniazid, rifampicin, ethambutol, pyrazinamide) remains the global reference. Therapy must always be tailored to drug susceptibility, especially in MDR- and XDR-TB. HIV-associated mycobacterial infections—including Mycobacterium tuberculosis (TB), disseminated Mycobacterium avium complex (MAC), and Mycobacterium leprae (M. leprae)—remain leading causes of morbidity and mortality in people living with HIV (PLWH). TB continues to account for the highest burden of AIDS-related deaths worldwide, while MAC and leprosy complicate care in advanced immunosuppression. This review synthesizes current evidence on epidemiology, clinical features, and management challenges of HIV–mycobacterial co-infections. We discuss drug-susceptible and drug-resistant TB therapies, drug–drug interactions with antiretroviral therapy (ART), and the clinical impact of immune reconstitution inflammatory syndrome (IRIS). Beyond established regimens, we highlight host-directed strategies such as metformin, glutathione augmentation, mTOR modulation, and vitamin D; immunotherapies including interferon-γ, GM-CSF, and IL-7; and therapeutic vaccines (M72/AS01E, MTBVAC, VPM1002) as promising adjuncts. Distinct from guideline-focused overviews, this review emphasizes non-tuberculous mycobacterial disease (NTM, including MAC) and leprosy in PLWH and synthesizes host-directed and adjunctive strategies with their translational prospects, including ART compatibility and IRIS. By integrating TB, NTM, and leprosy across the HIV care continuum, we highlight opportunities not treated in detail elsewhere—particularly HDT-enabled approaches and implementation considerations in PLWH. Full article
(This article belongs to the Special Issue Advances in Molecular Therapeutics for HIV Co-Infections)
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