Science AI Journal
Immunology and Microbiology · Research topic

Open research questions in HIV Research and Treatment

56 unresolved questions extracted from the limitations and future-work sections of 224 HIV Research and Treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • While Heplisav-B’s CpG 1018 adjuvant improves immunogenicity in PLWH, its mechanisms for overcoming HIV-related immune dysfunction are not yet defined.

    CpG-Adjuvanted Heplisav-B Induces Strong Th1-Biased Innate Responses Compared to Alum-Adjuvanted HBV Vaccines in PLWH 2308661 · 2026 · DOI

  • Although known to be critical for control of diverse bacterial and viral infections, neutrophil responses to HIV-1 and HIV-antibody ICs (HIV-ICs), remain poorly defined.

    Neutrophils Display Limited Antiviral Activity Against HIV-1 Immune Complexes 2307573 · 2026 · DOI

  • Although the underlying molecular mechanisms remain to be established, this exploratory model provides an alternative framework for investigating HIV-associated immune dysfunction and may stimulate future studies using lineage-tracing, single-cell transcriptomics, and epigenetic profiling to evaluate this proposed mechanism.

    Experimental Evidence for HIV-Associated Phenotypic Reprogramming of CD4⁺ T Cells: An Exploratory Immunological Study · 2026 · DOI

  • While the structural role of Gag and the enzymatic functions of GagPol are well described, little is known regarding the mechanisms underlying their cytosolic interactions, spatial organization, and relative incorporation into assembling particles.

    Developing a fluorescent derivative of GagPol as a tool for live-cell imaging of HIV-1 assembly · 2026 · DOI

  • However, the early events during HIV rectal transmission are not well understood and many questions remain, such as, does virus local amplification at the entry portal require for viral distal seeding? What is the spatiotemporal dissemination pattern across whole body? How do three viral forms, i.

    Analysis of SIV Spatiotemporal Dissemination Patterns in Rhesus Macaques During Early Rectal Transmission Demonstrates Systemic Infection Does Not Require Viral Local Amplification at the Entry Portal · 2026 · DOI

  • This preclinical proof-of-concept study supports further investigation of IgY-based oral immunization as a potential platform for HIV vaccine development.

    Oral Administration of Hyperimmune Eggs Induces Mucosal IgA Responses, Anti-Idiotypic Antibodies, and HIV-1 Neutralizing Activity: A Proof-of-Concept Preclinical Study · 2026 · DOI

  • It inhibits multiple steps of the viral life cycle; however, the molecular details of the effect of LEN on capsid structure and the mechanistic steps of the inhibition are not understood.

    Lenacapavir-induced lattice hyperstabilization is central to HIV-1 capsid failure at the nuclear pore complex and in the cytoplasm · 2026 · DOI

  • Further studies of infected microglia are likely to aid in understanding the pathogenesis of HAND and in evaluating therapeutic strategies to limit or eliminate HIV-induced neuropathogenesis.

    HIV-1 infection of human microglia activates inflammatory pathways associated with HIV-associated neurocognitive disorders (HAND) · 2026 · DOI

  • Although we demonstrate that Nef-EVs are sufficient to induce TRIM, other HIV proteins present in the blood of PLWH, such as Tat, may also contribute to, or even initiate, to which TRIM contributes to chronic inflammation in PLWH, as well as its persistence, remains unknown, and extrapolating from murine models is inherently challenging.

    HIV-1 Nef generates lasting innate immune memory in haematopoietic stem and progenitor cells in vivo · 2026 · DOI

  • Cellular metabolism regulates HIV/SIV replication and reservoir establishment, yet how infection and antiretroviral therapy initiation (ARTi) shape CD4 T cell metabolism in vivo remains poorly defined.

    Type I IFN reprograms CD4⁺ T cell lipid metabolism as an antiviral effector mechanism during acute HIV/SIV infection · 2026 · DOI

  • HIV-1 cure requires preventing viral rebound after treatment interruption, but quantitative criteria defining the rebound-competent reservoir are lacking.

    Inhibitory potential of autologous neutralizing antibodies sets quantitative limits on the rebound-competent HIV-1 reservoir · 2026 · DOI

  • While structural information is available for the membrane-proximal external region (MPER) and transmembrane domain (TMD), these regions remain comparatively understudied.

    Conformational Variability of HIV-1 Env Trimer and Viral Vulnerability · 2026 · DOI

  • As a successful human pathogen, it deploys various viral proteins to counteract host defenses and subjugate host machinery, but mechanisms underlying these complex HSV-host interactions are not fully understood.

    Multifaceted regulations of HSV-1 ICP0 on the Anti-Viral Restrictions Imposed by the Host Hippo Kinases Reprogramming · 2026 · DOI

  • While our findings highlight the possibility of Nef-mediated ARP2/3 inhibition in HIV-induced senescence, the roles of other viral proteins like Env and Gag, which also interact with the actin cytoskeleton, warrant further investigation.

    HIV Nef-mediated WAVE2-ARP2/3 inhibition underlies CD4 <sup>+</sup> T-cell lamellipodial abnormalities and immune dysfunction · 2026 · DOI

  • Post-transcriptional regulation mechanisms by which host anti-viral factors (like IFIT proteins and PKR) preferentially target viral RNA during stress granule formation have not been delineated at the single-granule resolution. Computational modeling combined with cryo-EM or super-resolution microscopy could elucidate selective recognition mechanisms.

    Stress granules at the crossroads of retroviral replication and antiviral immunity: mechanisms and therapeutic opportunities · 2026 · DOI

  • Drug candidates targeting stress granule assembly (via PKR activation and eIF2α phosphorylation) have been identified, but their neurotoxicity profiles and off-target effects on non-infected cells remain poorly characterized. Clinical translation requires systematic toxicology studies in astrocyte models to mitigate granule modulation-induced neurotoxicity.

    Stress granules at the crossroads of retroviral replication and antiviral immunity: mechanisms and therapeutic opportunities · 2026 · DOI

  • The translational consequences of PABP-mediated granule assembly during retroviral infection require quantitative validation in primary human cells beyond established cell culture models. Specific assessment is needed of how stress granule-mediated translational repression impacts both viral polyprotein synthesis and host innate immune factor production.

    Stress granules at the crossroads of retroviral replication and antiviral immunity: mechanisms and therapeutic opportunities · 2026 · DOI

  • Host RNA-binding protein-viral RNA interaction networks (particularly involving stress granule components like G3BP1 and TIAR) have not been comprehensively mapped across different retroviral species. Structure-function studies of these molecular interactions could identify novel druggable targets for therapeutic granule manipulation.

    Stress granules at the crossroads of retroviral replication and antiviral immunity: mechanisms and therapeutic opportunities · 2026 · DOI

  • The interplay between stress granule assembly/disassembly dynamics and m6A RNA modification patterns during retroviral infection has not been systematically characterized. Future work should map temporal correlations between m6A-mediated epigenetic control of viral RNA fate and stress granule component recruitment.

    Stress granules at the crossroads of retroviral replication and antiviral immunity: mechanisms and therapeutic opportunities · 2026 · DOI

  • The mechanisms by which stress granule manipulation differentially affects retroviral RNA translation versus host mRNA translation during infection remain unclear. Comparative studies are needed to determine if selective targeting of stress granule-mediated translation restriction can inhibit viral protein synthesis while preserving critical host antiviral responses.

    Stress granules at the crossroads of retroviral replication and antiviral immunity: mechanisms and therapeutic opportunities · 2026 · DOI

  • Future research should expand the study population to include patients with HBV coinfection and those with resistance to INSTIs and/or NNRTIs to assess whether findings generalize to these groups.

    Dynamic changes of monocytes-related immune activation in people with HIV switching to long-acting injectable cabotegravir plus rilpivirine · 2026 · DOI

  • The volumetric precision of ±5% in the flow cytometry counting method may introduce measurement variability that could affect the detection of subtle changes in monocyte subset populations.

    Dynamic changes of monocytes-related immune activation in people with HIV switching to long-acting injectable cabotegravir plus rilpivirine · 2026 · DOI

  • HIV-1 DNA quantification was performed only at T0 and T12, whereas monocyte activation markers were assessed at additional time points, creating an incomplete temporal picture of the relationship between these variables.

    Dynamic changes of monocytes-related immune activation in people with HIV switching to long-acting injectable cabotegravir plus rilpivirine · 2026 · DOI

  • The study excluded individuals with HBV coinfection, resistance to INSTIs and/or NNRTIs, and those under 18 years old, limiting the generalizability of findings to these populations.

    Dynamic changes of monocytes-related immune activation in people with HIV switching to long-acting injectable cabotegravir plus rilpivirine · 2026 · DOI

  • The pathogenesis of IRIS is poorly understood, but in recovering HIV patients, its initiation and progression seem to be primarily linked to an increase in CD4+ T-helper and CD8+ T-suppressor cell count and a reduction in T-regulatory cells, all endorsed by exaggerated cytokine release and activity.

    Immune Reconstitution Inflammatory Syndrome · 2011 · DOI

Most-cited papers in HIV Research and Treatment

Most recent work

Find a gap in your own HIV Research and Treatment sub-topic

This page shows what the HIV Research and Treatment literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.

Open the Research Gap Finder →

Related topics in Immunology and Microbiology

Immune cells in cancer
82 open questions
T-cell and B-cell Immunology
75 open questions
Psoriasis: Treatment and Pathogenesis
70 open questions
Antibiotic Use and Resistance
68 open questions
Reproductive tract infections research
66 open questions
interferon and immune responses
58 open questions
Immune Cell Function and Interaction
54 open questions
Bacterial Infections and Vaccines
52 open questions
56 open questions have been extracted from the limitations and future-work passages of 224 HIV Research and Treatment papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 120,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? A Tier 1–5 acceptance probability in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck prior-publication & salami-slicing risk across 8 sources.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.