Azam Bolhassani
94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
Editorial on the Research Topic
The global phenotypic diversity of HIV-1: implications for pathogenesis, vaccine, and cure
Antiretroviral therapy (ART) is under continuous development with the goal of long-term control of HIV replication using effective and well-tolerated drugs. On 29 February 2024, the WHO published an updated report about HIV drug resistance.
Despite the clinical success of antiretroviral therapy, there is no cure for HIV infection, yet. As reported, HIV vaccines in development are in early-stage clinical trials (1). Indeed, the global and regional genetic diversity of HIV-1 (i.e., its high genetic mutation and recombination rates) are a main challenge for HIV vaccine development. Thus, investigating the distribution of HIV subtypes/clades in different regions is essential.
To date, several immunotherapy approaches were considered to activate the immune system (e.g., CD8+ T cells and NK cells) and eradicate latently HIV-infected cells (i.e., elimination of the HIV reservoir) including: a) reactivation of the latently HIV-infected cells using epigenetic modulators (2, 3) or immunostimulators (e.g., toll-like receptor (TLR) agonists) (4, 5); b) combination of a potent latency reversal agent (e.g., Romidepsin) with an immune modulator (e.g., a therapeutic vaccine) (6 and 7); and c) the use of chimeric antigen receptors (CARs) for directly killing HIV-infected cells (8, 9). Thus, it is critical to determine which immunotherapy approaches have an important effect in elimination of latently HIV-infected cells.
At present, some studies aim to develop preventive HIV vaccines and also overcome antiretroviral drug resistance as a cure for HIV infection. Current approaches in the management of HIV infection include prevention/reversion of viral latency, modulation of immune responses, development of novel vaccines, and improvement of antiretroviral drugs in HIV patients (10, 11).
To address these critical areas in HIV management, this Research Topic focused on: a) Phenotypic and pathogenicity properties of newly identified/emerged HIV-1 strains; b) Susceptibility to innate/adaptive immune responses and broadly neutralizing antibodies (bNAbs); c) Treatment outcomes and drug resistance; and d) Outcomes of clinical trials, including vaccine, treatment, and functional cure. In total, four articles were published in association with these topics as follows. In Paper 1, Pei et al. recommended resistance testing before ART to improve effective treatment and reduce the spread of resistant viruses. Moreover, molecular networks were highlighted for their utility in identifying transmission clusters and enabling more precise interventions. In this study, authors detected 10 HIV-1 subtypes in heterosexually transmitted patients, and 7 subtypes in homosexually transmitted patients. CRF07_BC and CRF01_AE were the most common subtypes among patients. The drug resistance rates of heterosexual and homosexual individuals were 45.34% and 33.33%, respectively. The molecular transmission network showed that the clustering rates of homosexual and heterosexual individuals were 52.78% and 39.13%, respectively. In paper 2, Ma et al. showed that longitudinal trajectory analysis of multiple immune indicators (i.e., CD4 count, CD8 count and CD4/CD8 ratio) can be used to guide targeted interventions among susceptible populations. They described that the combination of CD4 count, CD8 count and CD4/CD8 ratio is essential to predict risk of mortality among HIV-positive individuals up to 96 months following initiation of ART. Among the four study groups (group 1: low CD4 and CD4/CD8 inversion, group 2: high CD8 and CD4/CD8 inversion, group 3: slow recovery of CD4 and CD4/CD8 inversion, and group 4: rapid increase of CD4 and normal CD4/CD8), groups 1 and 3 had increased risk of mortality. In addition, immune recovery was slower in male than in female and in older individuals than in younger individuals.
In paper 3, Dirajlal-Fargo et al. indicated that children with perinatally acquired HIV (PHIV) had higher T cell activation and damage in the gut integrity despite ART and viral suppression more than two years. Therefore, authors highlighted extensive research on development of newer ART regimens and early ART initiation in PHIV to decrease inflammation and prevent long-term comorbidities. In addition, it is critical that the links between intestinal barrier function, intestinal microbiota composition, and immune activation are determined to decrease potential comorbidities in HIV-infected children. In paper 4, Pan et al. represented the first molecular transmission network analysis of the HIV-1 subtype B circulating in China. They highlighted the importance of the combined molecular surveillance and epidemiology. Their data indicated that more than 99% of subtype B sequences belonged to Thai B. Phylogenetic and molecular network analyses revealed a common origin with neighboring regions in mainland China. In general, at least two coexisting transmission routes in most transmission clusters involve a greater challenge in controlling the prevalence of HIV-1 infection.
Altogether, the complexity of HIV-1 diversity establishes increasing challenges for development of preventive, therapeutic and functional cure approaches towards the goal to end the pandemic. We hope that four published scientific articles could provide new outlooks on studying HIV and AIDS from different perspectives including resistance testing before ART, longitudinal trajectory analysis of multiple immune indicators, development of newer ART regimens and early ART initiation in PHIV, and the importance of combined molecular surveillance and epidemiology.
Author contributions
AB: Writing – original draft, Writing – review & editing.
Conflict of interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Haynes BF, Wiehe K, Borrow P, Saunders KO, Korber B, Wagh K, et al. Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies. Nat Rev Immunol. (2023) 23:142–58. doi: 10.1038/s41577-022-00753-w
2. Spivak AM, Planelles V. HIV-1 eradication: Early trials (and tribulations). Trends Mol Med. (2016) 22:10–27. doi: 10.1016/j.molmed.2015.11.004
3. Kien N, Jonathan K. The sounds of silencing: dynamic epigenetic control of HIV latency. Curr Opin HIV AIDS. (2024) 19:102–9. doi: 10.1097/COH.0000000000000850
4. Martinsen JT, Gunst JD, Højen JF, Tolstrup M, Søgaard OS. The use of toll-like receptor agonists in HIV-1 cure strategies. Front Immunol. (2020) 11:1112. doi: 10.3389/fimmu.2020.01112
5. Rozman M, Zidovec-Lepej S, Jambrosic K, Babic M, Drmic Hofman I. Role of TLRs in HIV-1 infection and potential of TLR agonists in HIV-1 vaccine development and treatment strategies. Pathogens. (2023) 12:92. doi: 10.3390/pathogens12010092
6. Mothe B, Rosás-Umbert M, Coll P, Manzardo C, Puertas MC, Morón-López S, et al. HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: Safety, immunogenicity and effect on the viral reservoir (Study BCN02). Front Immunol. (2020) 11:823. doi: 10.3389/fimmu.2020.00823
7. Rosás-Umbert M, Ruiz-Riol M, Fernández MA, Marszalek M, Coll P, Manzardo C, et al. In vivo effects of romidepsin on T-cell activation, apoptosis and function in the BCN02 HIV-1 Kick&Kill clinical trial. Front Immunol. (2020) 11:418. doi: 10.3389/fimmu.2020.00418
8. Hajduczki A, Danielson DT, Elias DS, Bundoc V, Scanlan AW, Berger EA. A trispecific anti-HIV chimeric antigen receptor containing the CCR5 N-terminal region. Front Cell Infect Microbiol. (2020) 10:242. doi: 10.3389/fcimb.2020.00242
9. Zhou Y, Jadlowsky J, Baiduc C, Klattenhoff AW, Chen Z, Bennett AD, et al. Chimeric antigen receptors enable superior control of HIV replication by rapidly killing infected cells. PloS Pathog. (2023) 19:e1011853. doi: 10.1371/journal.ppat.1011853
10. Deeks SG, Archin N, Cannon P, Collins S, Jones RB, de Jong MAWP, et al. International AIDS Society (IAS) Global Scientific Strategy working group. Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy. Nat Med. (2021) 27:2085–98. doi: 10.1038/s41591-021-01590-5
Keywords: HIV-1, phenotypic diversity, pathogenesis, vaccine, antiretroviral therapy, drug resistance
Citation: Bolhassani A (2025) Editorial: The global phenotypic diversity of HIV-1: implications for pathogenesis, vaccine, and cure. Front. Immunol. 16:1572732. doi: 10.3389/fimmu.2025.1572732
Received: 07 February 2025; Accepted: 14 February 2025;
Published: 28 February 2025.
Edited and Reviewed by:
Pei-Hui Wang, Shandong University, ChinaCopyright © 2025 Bolhassani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Azam Bolhassani, YXphbS5ib2xoYXNzYW5pQHlhaG9vLmNvbQ==; QV9ib2xoYXNhbmlAcGFzdGV1ci5hYy5pcg==