Acquired immunodeficiency syndrome (AIDS) is the advanced clinical state of infection with human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2), not a synonym for every HIV infection. In the U.S. CDC surveillance framework, AIDS is HIV infection stage 3; this numbering is framework-specific. Persistent viral replication, mucosal immune injury, chronic immune activation, and progressive failure of CD4 T-cell homeostasis produce severe cell-mediated immunodeficiency. Subject to the framework's stage-0 precedence rule, AIDS is classified by severe CD4 depletion or an AIDS-defining illness and is manifested by opportunistic infections, selected malignancies, and sometimes severe HIV-associated neurologic disease. Combination antiretroviral therapy suppresses viral replication and permits immune reconstitution but does not eradicate long-lived cellular reservoirs.
Ask a research question about Acquired Immunodeficiency Syndrome. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
Conditions with similar clinical presentations that must be differentiated from Acquired Immunodeficiency Syndrome:
name: Acquired Immunodeficiency Syndrome
creation_date: '2025-12-04T16:57:31Z'
synonyms:
- AIDS
- Acquired immune deficiency syndrome
description: >-
Acquired immunodeficiency syndrome (AIDS) is the advanced clinical state of
infection with human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2),
not a synonym for every HIV infection. In the U.S. CDC surveillance framework,
AIDS is HIV infection stage 3; this numbering is framework-specific. Persistent
viral replication, mucosal immune injury, chronic immune activation, and
progressive failure of CD4 T-cell homeostasis produce severe cell-mediated
immunodeficiency. Subject to the framework's stage-0 precedence rule, AIDS is
classified by severe CD4 depletion or an AIDS-defining illness and is manifested
by opportunistic infections, selected malignancies, and sometimes severe
HIV-associated neurologic disease. Combination antiretroviral therapy suppresses
viral replication and permits immune reconstitution but does not eradicate
long-lived cellular reservoirs.
categories:
- Immunodeficiency Disorder
- Infectious Disease
disease_term:
preferred_term: AIDS
term:
id: MONDO:0012268
label: AIDS
definitions:
- name: CDC HIV stage-3 surveillance case definition
definition_type: CASE_DEFINITION
scope: United States public-health surveillance in people with confirmed HIV infection
description: >-
In the U.S. CDC framework, AIDS is HIV infection classified as stage 3. The
surveillance framework uses severe CD4 depletion and AIDS-defining clinical
conditions; it is intended for population surveillance and is not, by
itself, a clinical decision rule for an individual patient.
evidence:
- reference: PMID:24717910
reference_title: "Revised surveillance case definition for HIV infection--United States, 2014."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
A confirmed case can be classified in one of five HIV infection stages
(0, 1, 2, 3, or unknown); early infection, recognized by a negative HIV
test within 6 months of HIV diagnosis, is classified as stage 0, and
acquired immunodeficiency syndrome (AIDS) is classified as stage 3.
explanation: The CDC surveillance definition explicitly identifies AIDS as HIV infection stage 3.
- reference: PMID:24717910
reference_title: "Revised surveillance case definition for HIV infection--United States, 2014."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The surveillance case definition is intended primarily for monitoring the
HIV infection burden and planning for prevention and care on a population
level, not as a basis for clinical decisions for individual patients.
explanation: This states the intended population-surveillance scope and its clinical-use limitation.
- name: Historical adult and adolescent CD4-depletion threshold
definition_type: CASE_DEFINITION
scope: 1993 U.S. CDC expanded AIDS surveillance definition for adolescents and adults
description: >-
The 1993 expanded U.S. CDC surveillance definition for adolescents and
adults included HIV infection with a CD4 T-cell count below 200 cells per
microliter or a CD4 percentage below 14 percent.
evidence:
- reference: PMID:8093740
reference_title: From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Consistent with the 1993 revised classification system, CDC has also
expanded the AIDS surveillance case definition to include all HIV-infected
persons who have less than 200 CD4+ T-lymphocytes/microL, or a CD4+
T-lymphocyte percentage of total lymphocytes of less than 14.
explanation: The CDC publication gives the exact count and percentage thresholds.
infectious_agent:
- name: Human immunodeficiency virus 1
description: HIV-1 is one of the two human lentiviruses that can cause AIDS.
infectious_agent_term:
preferred_term: Human immunodeficiency virus 1
term:
id: NCBITaxon:11676
label: Human immunodeficiency virus 1
evidence:
- reference: PMID:22229120
reference_title: Origins of HIV and the AIDS pandemic.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Acquired immunodeficiency syndrome (AIDS) of humans is caused by two
lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2).
explanation: This review identifies HIV-1 as one of the two human lentiviruses that cause AIDS.
- name: Human immunodeficiency virus 2
description: >-
HIV-2 can also progress to AIDS, but its natural history and antiretroviral
susceptibility differ from HIV-1.
infectious_agent_term:
preferred_term: Human immunodeficiency virus 2
term:
id: NCBITaxon:11709
label: Human immunodeficiency virus 2
evidence:
- reference: PMID:22229120
reference_title: Origins of HIV and the AIDS pandemic.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Acquired immunodeficiency syndrome (AIDS) of humans is caused by two
lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2).
explanation: This review identifies HIV-2 as one of the two human lentiviruses that cause AIDS.
- reference: PMID:36982978
reference_title: "Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The course of HIV-2 infection is longer compared to HIV-1 infection, but
without effective antiretroviral therapy (ART), a substantial proportion
of infected patients will progress to AIDS and die.
explanation: This supports progression of untreated HIV-2 infection to AIDS.
progression:
- phase: Onset
notes: >-
Progression from untreated HIV infection to overt AIDS is variable and can
take many years. Acute HIV illness occurs much earlier and is not the onset
of AIDS.
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Disease progression in untreated human immunodeficiency virus (HIV)
infection can take many years, and it was originally hypothesized to be a
consequence of slow, viral-mediated CD4(+) T-cell destruction.
explanation: This review supports a long and variable untreated interval before overt immunodeficiency.
pathophysiology:
- name: Persistent HIV Infection and Replication
description: >-
HIV establishes ongoing infection in susceptible immune cells. Viral
replication drives pathogenesis, while the resulting immunodeficiency
reflects both direct viral effects and dysregulated host immune homeostasis.
cell_types:
- preferred_term: CD4-positive, alpha-beta T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
biological_processes:
- preferred_term: viral process
modifier: ABNORMAL
term:
id: GO:0016032
label: viral process
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Thus, the onset of overt immune deficiency appears to be intimately linked
with CD4(+) memory T-cell dynamics and reflects the complex interplay of
direct viral cytopathogenicity and the indirect effects of persistent
immune activation on CD4(+) memory T-cell proliferation, differentiation,
and survival.
explanation: This supports viral and host-homeostatic contributions to AIDS pathogenesis.
downstream:
- target: Early Mucosal CD4 T-Cell Loss and Gut Barrier Injury
description: Early infection preferentially damages mucosal CD4 memory T-cell compartments.
causal_link_type: DIRECT
evidence:
- reference: PMID:15955686
reference_title: Viral and host factors in the pathogenesis of HIV infection.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
During acute infection, massive depletion of CD4+CCR5+ memory T cells
within the mucosal-associated lymphoid tissue leads to major and
potentially irreversible damage to CD4+ T-cell-mediated immune functions.
explanation: This directly links early HIV infection to mucosal CD4 memory T-cell loss.
- target: Abortive HIV Infection and Caspase-1 Pyroptosis
description: >-
In ex vivo human lymphoid tissue, abortive infection of quiescent CD4
T cells triggers inflammatory caspase-1-mediated death.
causal_link_type: DIRECT
evidence:
- reference: PMID:24356306
reference_title: Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
The remaining over 95% of quiescent lymphoid CD4 T cells die by
caspase-1-mediated pyroptosis triggered by abortive viral infection.
explanation: The ex vivo study directly links abortive HIV infection to caspase-1 pyroptosis.
- target: CNS HIV Infection and Neuroinflammation
description: HIV can enter the CNS and initiate local inflammatory and neurotoxic processes.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Trafficking of infected immune cells into the central nervous system
evidence:
- reference: PMID:25604237
reference_title: "Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The well-accepted “Trojan horse” hypothesis suggests that the virus
enters mainly through CD4 T lymphocytes or possibly monocytes during
routine surveillance, only to go on infecting local cells of the CNS
(16, 17).
explanation: This review specifically supports immune-cell trafficking as a route of HIV entry into the CNS.
- target: Persistent Cellular HIV Reservoir
description: >-
Integrated, transcriptionally silent provirus establishes a cellular
reservoir that is refractory to suppressive ART.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Proviral integration and establishment of latency in long-lived host cells
evidence:
- reference: PMID:29744964
reference_title: Peering into the HIV reservoir.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The HIV cellular reservoir comprises cells with HIV-DNA integrated into
their genome, but trancriptionally silent, making the virus refractory
to cART and to the action of the immune system.
explanation: This review directly supports an integrated, transcriptionally silent reservoir refractory to ART.
- name: Early Mucosal CD4 T-Cell Loss and Gut Barrier Injury
description: >-
Acute HIV infection causes marked depletion of mucosal CD4 memory T cells,
persistent mucosal inflammation, and epithelial barrier injury.
cell_types:
- preferred_term: CD4-positive, alpha-beta T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
locations:
- preferred_term: small intestine
term:
id: UBERON:0002108
label: small intestine
evidence:
- reference: PMID:23297256
reference_title: Microbial translocation in the pathogenesis of HIV infection and AIDS.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
In vivo studies demonstrated that HIV/SIV-associated microbial
translocation results from a series of immunopathological events occurring
at the GI mucosa: (i) early and severe mucosal CD4(+) depletion, (ii)
mucosal immune hyperactivation/persistent inflammation; (iii) damage to
the integrity of the intestinal epithelium with enterocyte apoptosis and
tight junction disruption; and (iv) subverted the gut microbiome, with a
predominance of opportunistic bacteria.
explanation: This review describes the linked mucosal CD4 loss, inflammation, and epithelial injury.
downstream:
- target: Microbial Translocation and Chronic Immune Activation
description: Barrier disruption permits microbial products to reach the circulation and sustain innate immune activation.
causal_link_type: DIRECT
evidence:
- reference: PMID:23297256
reference_title: Microbial translocation in the pathogenesis of HIV infection and AIDS.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
In pathogenic simian immunodeficiency virus (SIV) and human
immunodeficiency virus (HIV) infections, the translocation of microbial
products from the gastrointestinal (GI) tract to portal and systemic
circulation has been proposed as a major driver of the chronic immune
activation that is associated with disease progression.
explanation: The source supports the proposed link while explicitly retaining mechanistic uncertainty.
- name: Microbial Translocation and Chronic Immune Activation
description: >-
Microbial products crossing the damaged gut barrier contribute to persistent
innate and adaptive immune activation during chronic HIV infection.
biological_processes:
- preferred_term: T cell activation
modifier: INCREASED
term:
id: GO:0042110
label: T cell activation
evidence:
- reference: PMID:23297256
reference_title: Microbial translocation in the pathogenesis of HIV infection and AIDS.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
While the mechanisms by which microbial translocation causes immune
activation remain controversial, a key pathogenic event appears to be
innate immunity activation via Toll-like receptors and other pathogen
recognition receptors.
explanation: This supports a contributory innate-activation mechanism while preserving uncertainty.
downstream:
- target: Progressive CD4 T-Cell Depletion and Homeostatic Failure
description: >-
Persistent immune activation disrupts CD4 memory-cell proliferation,
differentiation, survival, and regenerative homeostasis.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Dysregulated CD4 memory T-cell turnover and regeneration
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Thus, the onset of overt immune deficiency appears to be intimately linked
with CD4(+) memory T-cell dynamics and reflects the complex interplay of
direct viral cytopathogenicity and the indirect effects of persistent
immune activation on CD4(+) memory T-cell proliferation, differentiation,
and survival.
explanation: This review directly supports chronic activation as an indirect driver of CD4 homeostatic failure.
- name: Abortive HIV Infection and Caspase-1 Pyroptosis
description: >-
In ex vivo human lymphoid aggregates, abortive HIV-1 infection of quiescent
CD4 T cells activates caspase-1, causing inflammatory pyroptotic cell death.
This is a contributory experimental mechanism, not a universal quantitative
estimate for every person with AIDS.
cell_types:
- preferred_term: CD4-positive, alpha-beta T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
biological_processes:
- preferred_term: pyroptotic inflammatory response
modifier: INCREASED
term:
id: GO:0070269
label: pyroptotic inflammatory response
evidence:
- reference: PMID:24356306
reference_title: Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Pyroptosis corresponds to an intensely inflammatory form of programmed
cell death in which cytoplasmic contents and pro-inflammatory cytokines,
including IL-1β, are released.
explanation: The ex vivo study characterizes the inflammatory cell-death mechanism.
downstream:
- target: Progressive CD4 T-Cell Depletion and Homeostatic Failure
description: Pyroptotic death of abortively infected lymphoid CD4 T cells contributes to the depleted CD4 pool.
causal_link_type: DIRECT
evidence:
- reference: PMID:24356306
reference_title: Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
The remaining over 95% of quiescent lymphoid CD4 T cells die by
caspase-1-mediated pyroptosis triggered by abortive viral infection.
explanation: This directly supports pyroptosis-mediated CD4 loss in the ex vivo lymphoid-tissue system.
- name: Progressive CD4 T-Cell Depletion and Homeostatic Failure
description: >-
Direct viral effects and chronic immune activation eventually overwhelm
CD4 memory T-cell regeneration, lowering critical effector populations.
cell_types:
- preferred_term: CD4-positive, alpha-beta T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Ultimately, CD4(+) memory T-cell homeostasis fails and critical effector
populations decline below the level necessary to prevent OI.
explanation: This supports progressive failure of CD4 homeostasis and loss of protective effector cells.
downstream:
- target: Severe Cell-Mediated Immunodeficiency
description: Falling CD4 effector-cell numbers and function produce overt cellular immune failure.
causal_link_type: DIRECT
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The hallmark of acquired immunodeficiency syndrome (AIDS) pathogenesis is
a progressive depletion of CD4(+) T-cell populations in close association
with progressive impairment of cellular immunity and increasing
susceptibility to opportunistic infections (OI).
explanation: This directly connects progressive CD4 depletion with impaired cellular immunity.
- name: Severe Cell-Mediated Immunodeficiency
description: >-
Profound loss of CD4 T-cell number and function marks overt AIDS and
undermines immune control of opportunistic pathogens and oncogenic viruses.
cell_types:
- preferred_term: CD4-positive, alpha-beta T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Overall, these observations provide strong evidence that a profoundly
impaired cellular immune response due to depletion of CD4+T cells and loss
of CD4+T-cell function was the underlying cause of immunodeficiency present
in these patients.
explanation: This supports CD4 loss and dysfunction as the basis of severe cellular immunodeficiency.
downstream:
- target: Opportunistic Infection Susceptibility
description: Loss of CD4-dependent host defense permits opportunistic pathogens to cause severe disease.
causal_link_type: DIRECT
evidence:
- reference: PMID:23772614
reference_title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The hallmark of acquired immunodeficiency syndrome (AIDS) pathogenesis is
a progressive depletion of CD4(+) T-cell populations in close association
with progressive impairment of cellular immunity and increasing
susceptibility to opportunistic infections (OI).
explanation: This directly links severe cellular immune impairment to opportunistic-infection susceptibility.
- target: Loss of Oncogenic-Virus Immune Control
description: Immunodeficiency permits oncogenic coinfections to escape immune control and promote tumors.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Failure of immune surveillance against HHV-8, Epstein-Barr virus, and oncogenic human papillomavirus
evidence:
- reference: PMID:12525676
reference_title: AIDS-related malignancies.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
In acquired immunodeficiency due to the human immunodeficiency virus
(HIV), HIV itself rarely directly causes cancer; rather, it provides the
immunologic background against which other viruses can escape immune
control and induce tumors.
explanation: This review directly supports loss of immune control over oncogenic viruses as the cancer mechanism.
- name: Opportunistic Infection Susceptibility
description: >-
Severe cellular immunodeficiency permits AIDS-defining opportunistic
infections; Pneumocystis pneumonia and esophageal candidiasis are
representative manifestations rather than an exhaustive list.
evidence:
- reference: PMID:16182595
reference_title: "Pneumocystis: immune recognition and evasion."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Pulmonary infection caused by the opportunistic fungal organism
Pneumocystis continues to be a leading AIDS defining illness.
explanation: This identifies Pneumocystis pneumonia as a leading AIDS-defining opportunistic illness.
downstream:
- target: Pneumocystis jirovecii Pneumonia
description: Severe T-cell immunodeficiency permits pulmonary Pneumocystis infection.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Failure of coordinated innate and immune-mediated pulmonary fungal clearance
evidence:
- reference: PMID:16182595
reference_title: "Pneumocystis: immune recognition and evasion."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Host defense against Pneumocystis involves a delicate, concerted balance
between the inflammatory response and immune-mediated clearance.
explanation: This supports failure of immune-mediated clearance as the link from immunodeficiency to Pneumocystis pneumonia.
- target: Esophageal Candidiasis
description: Severe cellular immune dysfunction permits invasive Candida infection of the esophagus.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Failure of mucosal antifungal host defense
evidence:
- reference: PMID:17944709
reference_title: Invasive fungal infections among inpatients with acquired immune deficiency syndrome at a Chinese university hospital.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
IFIs included thrush, oesophageal candidiasis, fungal pneumonia,
cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in
the digestive tract, 71.8% of IFIs occurred in patients with
CD4(+)T-lymphocyte counts <100 cells mm(-3).
explanation: This cohort links esophageal candidiasis and other invasive fungal infections with severe CD4 depletion.
- name: Loss of Oncogenic-Virus Immune Control
description: >-
AIDS-associated immune dysfunction reduces surveillance of HHV-8,
Epstein-Barr virus, and oncogenic human papillomavirus, enabling selected
malignancies.
evidence:
- reference: PMID:12525676
reference_title: AIDS-related malignancies.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Immunodeficiency alters the risk of cancer. Specific types of immune
dysfunction are associated with different tumor risks, but most tumors are
related to oncogenic viruses.
explanation: This supports oncogenic-virus-associated malignancy in the immunodeficient state.
downstream:
- target: Kaposi Sarcoma
description: Kaposi sarcoma-associated herpesvirus is implicated in Kaposi sarcoma development.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- HHV-8-associated Kaposi sarcoma development
evidence:
- reference: PMID:8876905
reference_title: Oncological problems in AIDS--a review of the clinical features and management.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Kaposi's sarcoma-associated herpes virus is implicated in the
development of Kaposi's sarcoma, Epstein-Barr virus in systemic
non-Hodgkin's lymphoma as well as primary central nervous system
lymphoma and human papilloma virus in invasive cervical cancer.
explanation: This directly supports the association between HHV-8 and Kaposi sarcoma.
- target: AIDS-Related Non-Hodgkin Lymphoma
description: Epstein-Barr virus is implicated in systemic and primary-CNS AIDS-related lymphomas.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Epstein-Barr virus association with systemic and primary-CNS lymphoma
evidence:
- reference: PMID:8876905
reference_title: Oncological problems in AIDS--a review of the clinical features and management.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Kaposi's sarcoma-associated herpes virus is implicated in the
development of Kaposi's sarcoma, Epstein-Barr virus in systemic
non-Hodgkin's lymphoma as well as primary central nervous system
lymphoma and human papilloma virus in invasive cervical cancer.
explanation: This directly supports the association between EBV and systemic or primary-CNS lymphoma.
- target: Invasive Cervical Cancer
description: Oncogenic human papillomavirus is implicated in invasive cervical cancer.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Human papillomavirus association with invasive cervical cancer
evidence:
- reference: PMID:8876905
reference_title: Oncological problems in AIDS--a review of the clinical features and management.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Kaposi's sarcoma-associated herpes virus is implicated in the
development of Kaposi's sarcoma, Epstein-Barr virus in systemic
non-Hodgkin's lymphoma as well as primary central nervous system
lymphoma and human papilloma virus in invasive cervical cancer.
explanation: This directly supports the association between HPV and invasive cervical cancer.
- name: CNS HIV Infection and Neuroinflammation
description: >-
HIV can establish compartmentalized infection in CNS macrophage-lineage
cells. Local immune activation, neuroinflammation, and neurotoxicity can
contribute to severe HIV-associated cognitive disease.
cell_types:
- preferred_term: microglial cell
term:
id: CL:0000129
label: microglial cell
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
evidence:
- reference: PMID:25604237
reference_title: "Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Recent work suggests that the stage for HIV neuropathogenesis may be set
with initial viral entry into the CNS, followed by initiation of
pathogenetic processes including neuroinflammation and neurotoxicity, and
establishment of local, compartmentalized HIV replication that may reflect
a tissue reservoir for HIV.
explanation: This review supports CNS infection, neuroinflammation, and neurotoxicity.
downstream:
- target: AIDS Dementia Complex
description: Severe CNS HIV disease can culminate in HIV-associated dementia/AIDS dementia complex.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Macrophage and microglial activation, inflammatory mediator release, and neuronal dysfunction
evidence:
- reference: PMID:25604237
reference_title: "Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Early in the HIV epidemic, a large proportion of the neurological
manifestations of HIV presented as opportunistic CNS infections,
including toxoplasmosis and progressive multifocal leukoencephalopathy
(1). By 1987, the non-specific “subacute encephalitis” that widely
affected patients with HIV was identified as the AIDS dementia complex
(ADC, now termed HIV-associated dementia, or HAD), and was recognized as
a manifestation of HIV itself rather than that of an alternate infection
(2).
explanation: This supports AIDS dementia as an HIV manifestation while the exact mechanistic route remains multifactorial.
- name: Persistent Cellular HIV Reservoir
description: >-
Resting CD4 memory T cells and other cellular compartments can retain
integrated provirus during suppressive ART, preventing eradication and
enabling renewed infection if therapy stops.
cell_types:
- preferred_term: CD4-positive, alpha-beta T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
evidence:
- reference: PMID:29744964
reference_title: Peering into the HIV reservoir.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The HIV cellular reservoir comprises cells with HIV-DNA integrated into
their genome, but trancriptionally silent, making the virus refractory to
cART and to the action of the immune system.
explanation: This directly supports integrated, transcriptionally silent HIV persisting despite ART.
- reference: PMID:29744964
reference_title: Peering into the HIV reservoir.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Numerous reports have described that the main HIV cellular reservoir is
composed of resting CD4+ T-cells16–18. Importantly, replication-competent
provirus from the latent reservoir is capable of reigniting new rounds of
infection if therapy is interrupted4,5.
explanation: This supports resting CD4 T cells as a major reservoir and renewed infection after ART interruption.
- reference: PMID:37317962
reference_title: Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Outgrowth virus from parietal cortex MG in an individual with HIV
productively infected both MG and PBMCs.
explanation: Human rapid-autopsy tissue with ex vivo viral outgrowth supports replication-competent HIV in brain microglia.
phenotypes:
- name: Pneumocystis jirovecii Pneumonia
category: Respiratory
description: Pneumocystis jirovecii pneumonia is a representative AIDS-defining opportunistic infection.
diagnostic: true
phenotype_term:
preferred_term: Pneumocystis jirovecii pneumonia
term:
id: HP:0020102
label: Pneumocystis jirovecii pneumonia
evidence:
- reference: PMID:16182595
reference_title: "Pneumocystis: immune recognition and evasion."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Pulmonary infection caused by the opportunistic fungal organism
Pneumocystis continues to be a leading AIDS defining illness.
explanation: This identifies Pneumocystis pneumonia as an AIDS-defining illness.
- name: Esophageal Candidiasis
category: Gastrointestinal
description: Esophageal candidiasis is a representative AIDS-defining opportunistic infection.
diagnostic: true
evidence:
- reference: PMID:18366449
reference_title: Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The three most frequent initial ADIs were Pneumocystis carinii (jirovecii)
pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's
sarcoma (13.9%) in the pre-cART period.
explanation: This cohort explicitly identifies esophageal candidiasis as an initial AIDS-defining illness.
- name: Kaposi Sarcoma
category: Neoplasm
description: Kaposi sarcoma is an HHV-8-associated AIDS-defining malignancy.
diagnostic: true
phenotype_term:
preferred_term: Kaposi's sarcoma
term:
id: HP:0100726
label: Kaposi's sarcoma
evidence:
- reference: PMID:18366449
reference_title: Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The three most frequent initial ADIs were Pneumocystis carinii (jirovecii)
pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's
sarcoma (13.9%) in the pre-cART period.
explanation: This cohort identifies Kaposi sarcoma as an initial AIDS-defining illness.
- name: AIDS-Related Non-Hodgkin Lymphoma
category: Neoplasm
description: >-
Systemic and primary-CNS non-Hodgkin lymphomas are representative
AIDS-associated malignancies.
evidence:
- reference: PMID:8876905
reference_title: Oncological problems in AIDS--a review of the clinical features and management.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
They include Kaposi's sarcoma, systemic non-Hodgkin's lymphoma, primary
central nervous system lymphoma and invasive cervical cancer.
explanation: This review identifies systemic and CNS non-Hodgkin lymphomas among AIDS-associated malignancies.
- name: Invasive Cervical Cancer
category: Neoplasm
description: Invasive cervical cancer is an HPV-associated AIDS-defining condition.
diagnostic: true
evidence:
- reference: PMID:8093740
reference_title: From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
This expansion includes the addition of three clinical
conditions--pulmonary tuberculosis, recurrent pneumonia, and invasive
cervical cancer--and retains the 23 clinical conditions in the AIDS
surveillance case definition published in 1987; it is to be used by all
states for AIDS case reporting effective immediately.
explanation: The expanded CDC surveillance definition explicitly added invasive cervical cancer.
- name: AIDS Dementia Complex
category: Neurologic
description: >-
AIDS dementia complex, now commonly called HIV-associated dementia, is the
severe neurocognitive manifestation linked to advanced HIV disease.
evidence:
- reference: PMID:25604237
reference_title: "Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
By 1987, the non-specific “subacute encephalitis” that widely affected
patients with HIV was identified as the AIDS dementia complex (ADC, now
termed HIV-associated dementia, or HAD), and was recognized as a
manifestation of HIV itself rather than that of an alternate infection
(2).
explanation: This identifies AIDS dementia complex/HIV-associated dementia as a direct HIV manifestation.
biochemical:
- name: CD4 T-Cell Count
biomarker_term:
preferred_term: CD4 Expressing T Cell Count
term:
id: NCIT:C74608
label: CD4 Expressing T Cell Count
presence: Decreased
context: >-
Absolute count and percentage are U.S. CDC surveillance-stage measures with
age-specific thresholds. The count takes precedence, and percentage is used
only when the count is missing. Stage 0 and a qualifying opportunistic illness
can take precedence over the CD4 table. Values can rise after ART and must be
interpreted with clinical history.
readouts:
- target: Severe Cell-Mediated Immunodeficiency
relationship: READOUT_OF
direction: THRESHOLD_DEPENDENT
endpoint_context: DIAGNOSTIC
interpretation: >-
For a person aged 6 years or older who does not meet stage-0 criteria, a
CD4 count below 200 cells per microliter indicates U.S. CDC surveillance
stage 3; a CD4 percentage below 14 percent is used only when the count is
missing. Children younger than 6 years have age-specific stage-3 cutoffs.
evidence:
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
TABLE. HIV infection stage* based on age-specific CD4+ T-lymphocyte
count or CD4+ T-lymphocyte percentage of total lymphocytes
Stage
Age on date of CD4+ T-lymphocyte test
<1 yr 1–5 yrs ≥6 yrs
Cells/µL % Cells/µL % Cells/µL %
1 ≥1,500 ≥34 ≥1,000 ≥30 ≥500 ≥26
2 750–1,499 26–33 500–999 22–29 200–499 14–25
3 <750 <26 <500 <22 <200 <14
explanation: The official table supplies age-specific stage-3 CD4 count and percentage thresholds.
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The stage is based primarily on the CD4+ T-lymphocyte count; the CD4+
T-lymphocyte count takes precedence over the CD4 T-lymphocyte percentage,
and the percentage is considered only if the count is missing.
explanation: This establishes count precedence and percentage use only when the count is missing.
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
if the criteria for stage 0 are met, the stage is 0 regardless of
criteria for other stages (CD4 T-lymphocyte test results and
opportunistic illness diagnoses)
explanation: This establishes stage-0 precedence over CD4 results and stage-3-defining illnesses.
evidence:
- reference: PMID:8093740
reference_title: From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The Centers for Disease Control and Prevention (CDC) has revised the
classification system for HIV infection to emphasize the clinical
importance of the CD4+ T-lymphocyte count in the categorization of
HIV-related clinical conditions.
explanation: This establishes CD4 count as a central HIV-stage classification biomarker.
- name: HIV Viral Load
biomarker_term:
preferred_term: HIV Viral Load Measurement
term:
id: NCIT:C92544
label: HIV Viral Load Measurement
presence: Variable
context: >-
Plasma HIV RNA monitors viral replication and treatment response; values can
become suppressed with effective ART.
readouts:
- target: Persistent HIV Infection and Replication
relationship: PHARMACODYNAMIC_MARKER_OF
direction: POSITIVE
endpoint_context: PHARMACODYNAMIC
interpretation: Falling HIV RNA indicates pharmacodynamic suppression of viral replication by ART.
evidence:
- reference: PMID:36308326
reference_title: "Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients who started an InSTI achieved viral suppression and CD4+ T cell
count above 350 cells/mm3significantly earlier.
explanation: The advanced-HIV cohort uses viral suppression as a treatment-response readout.
evidence:
- reference: PMID:36308326
reference_title: "Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The main outcomes were mortality, virological effectiveness (percentage of
patients with viral load of ≤50 copies/mL) and immune restoration
(percentage of patients with CD4+ T cell count above 350 cells/mm3).
explanation: This supports viral load as a virologic-treatment outcome in advanced HIV disease.
diagnosis:
- name: Confirm HIV Infection and Differentiate HIV-1 from HIV-2
description: >-
AIDS classification first requires established HIV infection. Contemporary
multitest algorithms include differentiation of HIV-1 and HIV-2.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: NCIT:C18020
label: Diagnostic Procedure
results: Laboratory evidence confirms HIV infection and, where possible, distinguishes HIV-1 from HIV-2.
evidence:
- reference: PMID:24717910
reference_title: "Revised surveillance case definition for HIV infection--United States, 2014."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Laboratory criteria for defining a confirmed case now accommodate new
multitest algorithms, including criteria for differentiating between HIV-1
and HIV-2 infection and for recognizing early HIV infection.
explanation: This supports confirmation and type differentiation before stage classification.
- name: U.S. CDC CD4 Surveillance-Stage Classification
description: >-
After HIV confirmation, apply the age-specific U.S. CDC surveillance table.
Absolute CD4 count takes precedence; use percentage only if the count is
missing, and apply stage-0 precedence before later-stage criteria.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: NCIT:C18020
label: Diagnostic Procedure
results: >-
At age 6 years or older, count below 200 cells per microliter indicates stage
3 when stage-0 criteria do not apply; percentage below 14 percent is used only
when count is missing. Children younger than 6 years have higher age-specific
stage-3 cutoffs.
evidence:
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
TABLE. HIV infection stage* based on age-specific CD4+ T-lymphocyte
count or CD4+ T-lymphocyte percentage of total lymphocytes
Stage
Age on date of CD4+ T-lymphocyte test
<1 yr 1–5 yrs ≥6 yrs
Cells/µL % Cells/µL % Cells/µL %
1 ≥1,500 ≥34 ≥1,000 ≥30 ≥500 ≥26
2 750–1,499 26–33 500–999 22–29 200–499 14–25
3 <750 <26 <500 <22 <200 <14
explanation: The official table supplies age-specific stage-3 CD4 count and percentage thresholds.
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The stage is based primarily on the CD4+ T-lymphocyte count; the CD4+
T-lymphocyte count takes precedence over the CD4 T-lymphocyte percentage,
and the percentage is considered only if the count is missing.
explanation: This establishes count precedence and percentage use only when the count is missing.
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
if the criteria for stage 0 are met, the stage is 0 regardless of
criteria for other stages (CD4 T-lymphocyte test results and
opportunistic illness diagnoses)
explanation: This establishes stage-0 precedence before later-stage classification.
- name: Assessment for AIDS-Defining Illnesses
description: >-
In the U.S. CDC surveillance framework, evaluate confirmed HIV infection for
stage-3 clinical conditions, including specified opportunistic infections
and malignancies. This clinical route is distinct from diagnosing HIV
infection itself.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: NCIT:C18020
label: Diagnostic Procedure
results: >-
When stage-0 criteria are not met, a qualifying AIDS-defining illness
establishes stage 3 regardless of the CD4 result.
evidence:
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
reference_title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
If a stage-3–defining opportunistic illness has been diagnosed, then the
stage is 3 regardless of CD4 T-lymphocyte test results, unless the criteria
described below for stage 0 are met.
explanation: This directly states the opportunistic-illness rule and its stage-0 exception.
- reference: PMID:18366449
reference_title: Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The three most frequent initial ADIs were Pneumocystis carinii (jirovecii)
pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's
sarcoma (13.9%) in the pre-cART period.
explanation: This provides representative clinical AIDS-defining illnesses.
treatments:
- name: Combination Antiretroviral Therapy
action_category: THERAPEUTIC
description: >-
Individualized combination ART suppresses HIV replication. Contemporary
initial regimens for most adults use an integrase strand-transfer inhibitor
with nucleoside or nucleotide reverse-transcriptase inhibitor components;
regimen selection must account for clinical context, resistance, interactions,
and HIV type.
treatment_term:
preferred_term: Antiretroviral Therapy
term:
id: NCIT:C94631
label: Antiretroviral Therapy
target_mechanisms:
- target: Persistent HIV Infection and Replication
treatment_effect: INHIBITS
description: Combination ART suppresses active viral replication.
evidence:
- reference: PMID:36308326
reference_title: "Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients who started an InSTI achieved viral suppression and CD4+ T cell
count above 350 cells/mm3significantly earlier.
explanation: This advanced-HIV cohort directly supports antiretroviral-regimen suppression of active HIV replication.
- target: Severe Cell-Mediated Immunodeficiency
treatment_effect: RESTORES
description: Viral suppression permits partial CD4 immune reconstitution and reduces opportunistic disease.
evidence:
- reference: PMID:11424971
reference_title: Immune restoration and CD4+ T-cell function with antiretroviral therapies.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Suppression of HIV-1 replication results in both laboratory and clinical
evidence of immune restoration.
explanation: This review supports immune restoration after suppressive ART.
evidence:
- reference: PMID:39616604
reference_title: "Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society-USA Panel."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
For most people with HIV, initial regimens composed of an integrase strand
transfer inhibitor (InSTI), specifically bictegravir or dolutegravir, with
2 (and in some cases 1) nucleoside or nucleotide reverse transcriptase
inhibitors are recommended.
explanation: This provides current initial-regimen guidance for most adults with HIV.
- reference: PMID:36308326
reference_title: "Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In this large real-life prospective cohort study, a significant lower
mortality, earlier viral suppression and earlier immune reconstitution
were observed among patients with advanced HIV disease treated with InSTIs.
explanation: This advanced-HIV cohort supports viral suppression, immune reconstitution, and clinical benefit.
- reference: PMID:36982978
reference_title: "Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Antiretroviral drugs in clinical use were designed for HIV-1 and,
unfortunately, some do not work as well, or do not work at all, for HIV-2.
explanation: This supports HIV type-specific antiretroviral regimen selection.
notes: >-
Some antiretrovirals active against HIV-1 are ineffective against HIV-2;
HIV-2 treatment requires type-appropriate expert regimen selection.
- name: Context-Specific Opportunistic-Infection Prophylaxis
action_category: THERAPEUTIC
description: >-
Antimicrobial prophylaxis can reduce selected opportunistic infections in
people with advanced immunosuppression. The agent, CD4 threshold, pathogen,
geography, screening results, interactions, and concurrent ART determine the
appropriate regimen; there is no single universal prophylaxis bundle.
treatment_term:
preferred_term: preventative therapy
term:
id: NCIT:C15843
label: Preventive Intervention
target_mechanisms:
- target: Opportunistic Infection Susceptibility
treatment_effect: BYPASSES
description: >-
Prophylactic antimicrobials reduce selected infections during advanced
immunosuppression while ART is initiated.
evidence:
- reference: PMID:28723333
reference_title: Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients in the enhanced-prophylaxis group had significantly lower rates
of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or
esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new
hospitalization (P=0.03).
explanation: The trial supports clinical prevention; BYPASSES denotes prevention despite, rather than correction of, the immune deficit.
evidence:
- reference: PMID:28723333
reference_title: Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients in the enhanced-prophylaxis group had significantly lower rates
of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or
esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new
hospitalization (P=0.03).
explanation: The trial documents condition-specific benefits of the evaluated prophylaxis bundle.
context: >-
The cited REALITY trial enrolled ART-naive participants in Uganda, Zimbabwe,
Malawi, and Kenya with CD4 counts below 100 cells per cubic millimeter.
differential_diagnoses:
- name: HIV Infection Without AIDS
description: >-
Confirmed HIV infection is broader than AIDS. In U.S. CDC surveillance,
early infection can be stage 0, other cases can be stage 1, 2, or unknown,
and AIDS is stage 3.
distinguishing_features:
- Confirmed HIV infection alone does not establish AIDS.
- Apply the surveillance framework's stage rules rather than inferring AIDS from HIV positivity alone.
evidence:
- reference: PMID:24717910
reference_title: "Revised surveillance case definition for HIV infection--United States, 2014."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
A confirmed case can be classified in one of five HIV infection stages
(0, 1, 2, 3, or unknown); early infection, recognized by a negative HIV
test within 6 months of HIV diagnosis, is classified as stage 0, and
acquired immunodeficiency syndrome (AIDS) is classified as stage 3.
explanation: This explicitly distinguishes AIDS/stage 3 from other stages of confirmed HIV infection.
- name: Idiopathic CD4 Lymphocytopenia
description: Rare CD4 lymphocytopenia syndrome described in HIV-negative patients.
distinguishing_features:
- HIV testing is negative.
- Other diseases and drugs remain differential considerations.
evidence:
- reference: PMID:16763460
reference_title: Idiopathic CD4 lymphocytopenia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Idiopathic CD4 lymphocytopenia is very rare. The clinical significance of
low CD4 cell counts in HIV negative patients still awaits its systematic
analysis.
explanation: This review describes the rarity of idiopathic CD4 lymphocytopenia in HIV-negative patients.
- reference: PMID:16763460
reference_title: Idiopathic CD4 lymphocytopenia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The differential diagnosis of this condition in adults comprises primarily
HIV infection and less often other diseases or drugs.
explanation: This supports HIV, other diseases, and drugs as differential considerations.
- name: Secondary Non-HIV CD4 Lymphocytopenia
description: >-
Infections, autoimmune disease, immunosuppressive treatment, and lymphoma
can produce severe CD4 lymphocytopenia without HIV/AIDS.
distinguishing_features:
- HIV testing is negative.
- A non-HIV disease, infection, or medication explains the immune abnormality.
evidence:
- reference: PMID:16763460
reference_title: Idiopathic CD4 lymphocytopenia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
In adults, HIV is certainly the most common cause of CD4 lymphocytopenia,
but other causes, such as infections, autoimmune diseases,
immunosuppressive therapy, lymphoma and idiopathic forms need to be
considered.
explanation: This review explicitly lists major non-HIV causes of CD4 lymphocytopenia.
notes: >-
AIDS is an advanced state caused by HIV infection; it is not transmitted
independently, so HIV transmission routes are not duplicated as AIDS
transmission records. No global prevalence value is asserted because HIV
prevalence is not interchangeable with the prevalence of AIDS.
The listed AIDS-defining illnesses are representative rather than exhaustive,
and treatment of each diagnosed infection or malignancy remains
condition-specific. Tangential drug-design models and incorrectly annotated
protein structures were removed because they did not model or depict the
claimed AIDS-specific mechanisms.
datasets: []
references:
- reference: PMID:11424971
title: Immune restoration and CD4+ T-cell function with antiretroviral therapies.
- reference: PMID:12525676
title: AIDS-related malignancies.
- reference: PMID:15955686
title: Viral and host factors in the pathogenesis of HIV infection.
- reference: PMID:16182595
title: "Pneumocystis: immune recognition and evasion."
- reference: PMID:16763460
title: Idiopathic CD4 lymphocytopenia.
- reference: PMID:17944709
title: Invasive fungal infections among inpatients with acquired immune deficiency syndrome at a Chinese university hospital.
- reference: PMID:18366449
title: Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy.
- reference: PMID:22229120
title: Origins of HIV and the AIDS pandemic.
- reference: PMID:23297256
title: Microbial translocation in the pathogenesis of HIV infection and AIDS.
- reference: PMID:23772614
title: "CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure."
- reference: PMID:24356306
title: Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
- reference: PMID:24717910
title: "Revised surveillance case definition for HIV infection--United States, 2014."
- reference: PMID:25604237
title: "Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)."
- reference: PMID:28723333
title: Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.
- reference: PMID:29744964
title: Peering into the HIV reservoir.
- reference: PMID:36308326
title: "Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens."
- reference: PMID:36982978
title: "Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds."
- reference: PMID:37317962
title: Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy.
- reference: PMID:39616604
title: "Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society-USA Panel."
- reference: PMID:8093740
title: From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.
- reference: PMID:8876905
title: Oncological problems in AIDS--a review of the clinical features and management.
- reference: url:https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf
title: "https://www.cdc.gov/mmwr/pdf/rr/rr6303.pdf"
Pathophysiology description (current understanding, 2023–2025 priorities) AIDS is the clinical end-stage of chronic HIV infection, driven by sustained viral replication, establishment of long-lived latent reservoirs, progressive immune dysfunction with CD4+ T-cell depletion, and chronic inflammation. HIV entry requires binding of gp120 to CD4 and a chemokine co-receptor (most commonly CCR5 or CXCR4), followed by fusion and delivery of the capsid core. Reverse transcription produces a DNA copy that integrates into host chromatin, enabling lifelong persistence as a provirus. Latent, intact proviruses in long-lived cells are the principal barrier to cure and persist through clonal expansion and sanctuary site protection. Chronic immune activation and mucosal barrier damage—especially in the gut—propagate systemic inflammation. Tissue reservoirs include lymphoid tissues (lymph node follicles, GALT), the CNS (microglia/macrophages), and myeloid lineages that contribute to persistence despite antiretroviral therapy (ART). Emerging evidence highlights inflammasome/pyroptosis pathways as relevant to CD4+ T-cell loss and as host-directed therapeutic targets. (moezpoor2024helporhinder pages 22-23, yildirir2024smacmimeticssensitize pages 24-31, lau2025hivandthe pages 1-2, armanitourret2024immunetargetingof pages 16-18, holloway2024inhibitionofcaspase pages 1-2, mohammadzadeh2025hivpersistencein pages 37-43, yildirir2024smacmimeticssensitize pages 191-196, calado2024decipheringthemechanisms pages 199-203)
Core pathophysiology 1) Viral entry, uncoating, reverse transcription - Entry: HIV uses CD4 with CCR5 or CXCR4 co-receptors to infect target cells; tropism differences reflect co-receptor usage and receptor density on T cells and myeloid cells, shaping early tissue targeting. Reviews summarizing cell-entry and target cell specificity emphasize memory CD4+ T cells and macrophages as critical targets. (Moezpoor & Stevenson 2024, Viruses; URL: https://doi.org/10.3390/v16081281) (moezpoor2024helporhinder pages 22-23) - Early replication steps: Capsid stability and uncoating are tightly coupled to efficient reverse transcription; reverse-transcribed viral DNA is transported to the nucleus for integration. Contemporary reviews integrate these early replication dynamics within the broader pathogenesis framework. (moezpoor2024helporhinder pages 22-23)
2) Integration, latency, and reservoirs - Latency: Integration into host chromatin creates a transcriptionally silent provirus; intact latent genomes can persist for years despite ART. Persisters are shaped by integration site, local chromatin, and host transcriptional state. (Armani‑Tourret et al., Nat Rev Microbiol 2024; URL: https://doi.org/10.1038/s41579-024-01010-8) (armanitourret2024immunetargetingof pages 16-18) - Clonal expansion and reservoir phenotypes: Clonal proliferation of infected cells underlies reservoir maintenance; single-cell and multi-omic studies reveal phenotypic signatures (e.g., effector memory programs, immune selection markers) of reservoir cells and demonstrate that transcriptionally active proviruses are negatively selected over time on ART. (Armani‑Tourret et al., 2024) (armanitourret2024immunetargetingof pages 20-22) - Tissue reservoirs and follicular immune privilege: The B-cell follicle in lymph nodes harbors tFollicular helper (Tfh)–rich reservoirs within a partially immune-privileged microenvironment, impeding CD8+ T-cell surveillance. Spatial reservoir mapping emphasizes similar proviral make-up in lymph nodes and blood with trafficking between compartments. (Zaman et al., mBio 2024; URL: https://doi.org/10.1128/mbio.01909-24) (armanitourret2024immunetargetingof pages 16-18) - Gut reservoirs: The intestinal immune compartment is infected early, enriched for CCR5+ memory CD4+ T cells (including Th17/Th22 and tissue‑resident TRM) and remains a key latent reservoir with unique pharmacologic and immunologic constraints; gut‑targeted cure strategies are under investigation. (Lau et al., Front Immunol 2025; URL: https://doi.org/10.3389/fimmu.2025.1650852) (lau2025hivandthe pages 1-2) - Myeloid/CNS reservoirs: Persistent reservoirs in microglia and tissue macrophages are increasingly recognized in humans and animal models; myeloid reservoir biology includes mechanisms of entry, replication competence, and resistance to immune clearance. (Armani‑Tourret et al., 2024; Castillo et al., Curr Clin Microbiol Rep 2024; URL: https://doi.org/10.1007/s40588-024-00234-9) (armanitourret2024immunetargetingof pages 16-18, castillo2024myeloidcellreservoirs pages 9-10)
3) Innate restriction factors and viral antagonists - Established host restriction factors acting at multiple stages include APOBEC3 family, SAMHD1, TRIM5α, tetherin, and SERINC5. HIV-1 accessory proteins counter these defenses: Vif antagonizes APOBEC3, Vpu antagonizes tetherin and modulates host signaling and receptor turnover, and Nef modulates CD4 and MHC-I. Contemporary reviews underscore the expanding landscape of restriction factors and viral countermeasures. (Moezpoor & Stevenson 2024, Viruses; Kmiec & Kirchhoff 2024, J Mol Cell Biol; URLs: https://doi.org/10.3390/v16081281; https://doi.org/10.1093/jmcb/mjae005) (moezpoor2024helporhinder pages 22-23)
4) CD4+ T-cell loss and inflammasome/pyroptosis - Mechanistic link: Caspase-1–dependent inflammasome activation can drive pyroptotic death of CD4+ T cells and propagate inflammation; in vivo pharmacologic inhibition of caspase‑1/4 (VX‑765) in humanized mice limited CD4+ T‑cell loss, reduced tissue viral load, and upregulated antiviral restriction factors (e.g., SAMHD1, APOBEC3A), supporting host-directed strategies to mitigate immune damage. (Holloway et al., Retrovirology 2024; URL: https://doi.org/10.1186/s12977-024-00641-2) (holloway2024inhibitionofcaspase pages 1-2)
5) Chronic immune activation and gut barrier dysfunction - Gut damage and microbial translocation: HIV disrupts gut mucosal integrity early, causing loss of Th17/Th22 cells, epithelial tight junction alteration, and increased translocation of microbial products that sustain systemic immune activation; despite ART, inflammation is reduced but not normalized. Systematic and mechanistic reviews link dysbiosis/translocation markers (e.g., LPS, sCD14) to non‑AIDS comorbidities. (Nganou‑Makamdop & Douek, Pathogens & Immunity 2024; URL: https://doi.org/10.20411/pai.v9i1.693; Cann et al., PLoS One 2024; URL: https://doi.org/10.1371/journal.pone.0308859) (lau2025hivandthe pages 1-2, armanitourret2024immunetargetingof pages 16-18)
6) Disease progression and clinical phenotypes - Natural history and OIs: Progressive CD4+ T-cell loss (often over years without ART) culminates in AIDS-defining opportunistic infections and malignancies; persistent immune activation and tissue reservoirs contribute to morbidity even under ART. Clinical guidance documents emphasize comprehensive management of pathogenesis-linked complications (OIs, IRIS, immune non‑response). (Chinese Guidelines 2024; URLs: https://doi.org/10.1097/id9.0000000000000152; https://doi.org/10.1097/cm9.0000000000003383) (armanitourret2024immunetargetingof pages 16-18) - CNS involvement: HIV invades the CNS early; microglial/macrophage reservoirs and immune-privileged niches contribute to persistent neuroinflammation and HIV-associated neurocognitive disorders, even with plasma suppression. Reviews summarize persistence mechanisms and therapeutic implications. (Calado 2024; Mohammadzadeh 2025) (calado2024decipheringthemechanisms pages 199-203, mohammadzadeh2025hivpersistencein pages 37-43)
Key molecular players - Genes/proteins (HGNC): - Entry/host receptors: CD4 (HGNC:1678), CCR5 (HGNC:1606), CXCR4 (HGNC:2561) (moezpoor2024helporhinder pages 22-23) - Viral enzymes/proteins: Gag-Pol (capsid/RT/IN), Env (gp120/gp41), Vif, Vpu, Nef (moezpoor2024helporhinder pages 22-23) - Host restriction: APOBEC3G (HGNC:17204), SAMHD1 (HGNC:28706), TRIM5 (HGNC:16212), BST2/tetherin (HGNC:1119), SERINC5 (HGNC:30458) (moezpoor2024helporhinder pages 22-23) - Inflammasome/caspases: Caspase‑1 (HGNC:1504), Caspase‑4 (HGNC:1502) (holloway2024inhibitionofcaspase pages 1-2) - Chemical entities (ChEBI): antiretrovirals (e.g., nucleos(t)ide analogues; integrase inhibitors), inflammasome inhibitor VX‑765 (as a representative experimental agent), LPS as translocation biomarker (holloway2024inhibitionofcaspase pages 1-2, lau2025hivandthe pages 1-2) - Cell types (CL): memory CD4+ T cells (CL:0000907), T follicular helper cells (CL:0002038), tissue‑resident memory T cells (CL:0000913), macrophages (CL:0000235), microglia (CL:0000129) (armanitourret2024immunetargetingof pages 16-18, lau2025hivandthe pages 1-2, castillo2024myeloidcellreservoirs pages 9-10) - Anatomical locations (UBERON): lymph node (UBERON:0000029), B‑cell follicle/germinal center (UBERON:0002367), small intestine/colon mucosa (UBERON:0002108; UBERON:0001155), brain (UBERON:0000955) (lau2025hivandthe pages 1-2, armanitourret2024immunetargetingof pages 16-18, mohammadzadeh2025hivpersistencein pages 37-43)
Biological processes (GO terms; disrupted in AIDS) - Viral entry via membrane fusion (GO:0008649); chemokine receptor binding (GO:0008009) (moezpoor2024helporhinder pages 22-23) - Reverse transcription (GO:0006278) and integration into host DNA (GO:0015074) (moezpoor2024helporhinder pages 22-23) - Negative regulation of viral genome replication by host restriction (GO:0045071) (moezpoor2024helporhinder pages 22-23) - Pyroptosis and inflammasome complex assembly (GO:0070269; GO:0061702) (holloway2024inhibitionofcaspase pages 1-2) - Epithelial barrier maintenance and response to lipopolysaccharide (GO:0060729; GO:0032496) (lau2025hivandthe pages 1-2) - T-cell activation/differentiation and memory cell maintenance (GO:0042110; GO:0002285) (armanitourret2024immunetargetingof pages 16-18)
Cellular components (GO) - Plasma membrane (GO:0005886) for receptor/coreceptor entry (moezpoor2024helporhinder pages 22-23) - Viral capsid and pre-integration complex (GO:0019030; GO:0019031) (moezpoor2024helporhinder pages 22-23) - Nuclear chromatin (GO:0000785) for integration/latency (armanitourret2024immunetargetingof pages 16-18) - Inflammasome complex (GO:0061702) (holloway2024inhibitionofcaspase pages 1-2)
Disease progression (sequence of events) - Acute infection: mucosal infection and rapid seeding of GALT, early CNS invasion; profound depletion of CCR5+ memory CD4+ T cells in gut; establishment of latent provirus in long‑lived cells. (lau2025hivandthe pages 1-2, calado2024decipheringthemechanisms pages 199-203) - Chronic infection on ART: plasma viremia suppressed; reservoirs persist via clonal expansion, tissue sanctuaries (lymph node follicles, gut, CNS), and immune evasion; dysbiosis and microbial translocation sustain systemic inflammation. (armanitourret2024immunetargetingof pages 16-18, lau2025hivandthe pages 1-2) - Advanced disease/AIDS (without effective ART): severe CD4+ T‑cell depletion, opportunistic infections/malignancies; in some settings, CNS escape/persistence contributes to neurocognitive impairment. (mohammadzadeh2025hivpersistencein pages 37-43)
Phenotypic manifestations (HP terms; mechanistic links) - Opportunistic infections (HP:0004322) and recurrent infections (HP:0002719) reflect severe CD4+ T‑cell depletion and mucosal barrier failure (armanitourret2024immunetargetingof pages 16-18) - Lymphopenia (HP:0001888) and reduced CD4 count (HP:0040084) due to cytopathic effects and pyroptosis/inflammasome activation (holloway2024inhibitionofcaspase pages 1-2) - Chronic diarrhea/weight loss (HP:0002027; HP:0001824) linked to gut mucosal damage and microbial translocation (lau2025hivandthe pages 1-2) - Cognitive impairment (HP:0100543) and neuroinflammation due to CNS reservoirs/persistence (mohammadzadeh2025hivpersistencein pages 37-43, calado2024decipheringthemechanisms pages 199-203) - Cardiometabolic comorbidities (e.g., atherosclerosis risk) associated with chronic inflammation and endothelial dysfunction post-ART (mechanistic reviews) (lau2025hivandthe pages 1-2)
Current applications and real-world implementations - ART suppresses viremia but does not eradicate reservoirs; cure strategies pursue “shock-and‑kill,” “block‑and‑lock,” immune targeting of reservoir cells, and anatomically targeted interventions (e.g., gut strategies). (Armani‑Tourret et al., 2024; Lau et al., 2025) (armanitourret2024immunetargetingof pages 16-18, lau2025hivandthe pages 1-2) - Host-directed therapy targeting inflammasomes/caspases shows promise preclinically to limit CD4 loss and reduce tissue viral burden. (Holloway et al., 2024) (holloway2024inhibitionofcaspase pages 1-2) - Clinical guidance emphasizes comprehensive management of OIs, IRIS, incomplete immune reconstitution, and whole-course management of HIV infection. (Chinese Guidelines 2024; URLs above) (armanitourret2024immunetargetingof pages 16-18)
Recent developments (2023–2025) - Single-cell/multi-omic reservoir mapping reveals phenotypic programs and immune selection signatures of persistent, intact proviruses and highlights antigen-driven clonal selection. (Armani‑Tourret et al., 2024) (armanitourret2024immunetargetingof pages 20-22) - Spatial reservoir insights in lymph node follicles support the concept of partial immune privilege protecting infected cells from cytotoxic clearance. (Zaman et al., 2024) (armanitourret2024immunetargetingof pages 16-18) - Gut-focused persistence remains a high‑priority target for cure research, with emphasis on Th17/Th22 loss, dysbiosis, and tissue‑tailored interventions. (Lau et al., 2025; Cann et al., 2024) (lau2025hivandthe pages 1-2, yildirir2024smacmimeticssensitize pages 191-196) - Myeloid/CNS reservoirs in humans further consolidate the role of microglia and macrophages in long‑term persistence despite suppressive ART. (Armani‑Tourret et al., 2024; Castillo et al., 2024) (armanitourret2024immunetargetingof pages 16-18, castillo2024myeloidcellreservoirs pages 9-10)
Expert opinions and authoritative analyses - Nature Reviews Microbiology and other authoritative reviews argue that targeting reservoir cell phenotypes and tissue microenvironments (follicle immune privilege, gut mucosa) will be essential to elimination strategies. (Armani‑Tourret et al., 2024) (armanitourret2024immunetargetingof pages 16-18, armanitourret2024immunetargetingof pages 20-22) - Pathogens & Immunity reviews synthesize gut mucosa–microbiome–immunity interactions as central to persistent inflammation and immune recovery. (Nganou‑Makamdop & Douek, 2024) (armanitourret2024immunetargetingof pages 16-18)
Relevant statistics and data (where recent evidence available) - Systematic reviews in 2024 document associations between gut dysbiosis/translocation markers (e.g., LPS, sCD14) and noncommunicable disease outcomes in people with HIV on ART. (Cann et al., PLoS One 2024; URL: https://doi.org/10.1371/journal.pone.0308859) (yildirir2024smacmimeticssensitize pages 191-196) - Experimental in vivo evidence: caspase‑1/4 inhibition in humanized mice reduced tissue viral loads and preserved CD4+ T cells, with transcriptomic elevation of host restriction factors. (Holloway et al., 2024) (holloway2024inhibitionofcaspase pages 1-2)
Evidence items with PMIDs/URLs (selected, supporting quotes where available) - “The intestinal immune compartment plays a central role in HIV pathogenesis… HIV persists indefinitely in latently infected cells, commonly found in the intestinal tract…” (Lau et al., Frontiers in Immunology, 2025; URL above) (lau2025hivandthe pages 1-2) - “Pharmacologic inhibition of caspase-1/4… limited CD4+ T cell loss… reduced viral load… upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A.” (Holloway et al., Retrovirology, 2024; URL above) (holloway2024inhibitionofcaspase pages 1-2) - “Monocyte-derived macrophages contain persistent latent HIV reservoirs… Brain microglia serve as a persistent HIV reservoir.” (Armani‑Tourret et al., Nat Rev Microbiol, 2024; URL above) (armanitourret2024immunetargetingof pages 16-18) - “The gut microbiome… associated with markers of microbial translocation (LPS, sCD14)… linked to noncommunicable disease outcomes in PWH.” (Cann et al., PLoS One, 2024; URL above) (yildirir2024smacmimeticssensitize pages 191-196)
Knowledge-base–ready annotations - HGNC: CD4 (HGNC:1678); CCR5 (HGNC:1606); CXCR4 (HGNC:2561); APOBEC3G (HGNC:17204); SAMHD1 (HGNC:28706); TRIM5 (HGNC:16212); BST2 (HGNC:1119); SERINC5 (HGNC:30458) (moezpoor2024helporhinder pages 22-23) - GO Processes: viral entry via membrane fusion (GO:0008649); reverse transcription (GO:0006278); DNA integration (GO:0015074); negative regulation of viral replication (GO:0045071); pyroptosis (GO:0070269); inflammasome complex assembly (GO:0061702) (moezpoor2024helporhinder pages 22-23, holloway2024inhibitionofcaspase pages 1-2) - GO Cellular Components: plasma membrane (GO:0005886); viral capsid (GO:0019030); pre‑integration complex (GO:0019031); nuclear chromatin (GO:0000785); inflammasome complex (GO:0061702) (moezpoor2024helporhinder pages 22-23, holloway2024inhibitionofcaspase pages 1-2) - CL (cell types): memory CD4+ T cell (CL:0000907); Tfh (CL:0002038); TRM (CL:0000913); macrophage (CL:0000235); microglia (CL:0000129) (armanitourret2024immunetargetingof pages 16-18, castillo2024myeloidcellreservoirs pages 9-10) - UBERON (anatomy): lymph node (UBERON:0000029); germinal center (UBERON:0002367); small intestine (UBERON:0002108); colon (UBERON:0001155); brain (UBERON:0000955) (lau2025hivandthe pages 1-2, armanitourret2024immunetargetingof pages 16-18) - HP (phenotypes): Opportunistic infections (HP:0004322); Lymphopenia (HP:0001888); Decreased CD4+ T cells (HP:0040084); Chronic diarrhea (HP:0002027); Cognitive impairment (HP:0100543) (lau2025hivandthe pages 1-2, holloway2024inhibitionofcaspase pages 1-2, mohammadzadeh2025hivpersistencein pages 37-43)
Notes on limitations and open questions - Some mechanistic areas (e.g., precise cell-intrinsic drivers of nuclear uncoating, CARD8 inflammasome roles, and full catalogs of reservoir integration sites in diverse tissues) remain active research areas. The cited 2024–2025 reviews and preclinical data converge on targeting tissue microenvironments (follicle, gut) and host inflammatory pathways alongside direct antiviral strategies. (armanitourret2024immunetargetingof pages 16-18, holloway2024inhibitionofcaspase pages 1-2, lau2025hivandthe pages 1-2)
Citations (URLs and publication dates embedded above; supporting IDs): (moezpoor2024helporhinder pages 22-23, yildirir2024smacmimeticssensitize pages 24-31, lau2025hivandthe pages 1-2, armanitourret2024immunetargetingof pages 16-18, holloway2024inhibitionofcaspase pages 1-2, mohammadzadeh2025hivpersistencein pages 37-43, yildirir2024smacmimeticssensitize pages 191-196, calado2024decipheringthemechanisms pages 199-203, castillo2024myeloidcellreservoirs pages 9-10, armanitourret2024immunetargetingof pages 20-22)
References
(moezpoor2024helporhinder pages 22-23): Michael Rameen Moezpoor and Mario Stevenson. Help or hinder: protein host factors that impact hiv-1 replication. Viruses, Aug 2024. URL: https://doi.org/10.3390/v16081281, doi:10.3390/v16081281. This article has 4 citations and is from a poor quality or predatory journal.
(yildirir2024smacmimeticssensitize pages 24-31): B Molyer Yildirir. Smac mimetics sensitize hiv-infected cells to mg1-mediated death. Unknown journal, 2024.
(lau2025hivandthe pages 1-2): Jillian S. Y. Lau, Sharon R. Lewin, and Sushama Telwatte. Hiv and the gut: implications for hiv persistence, immune dysfunction and cure strategies. Frontiers in Immunology, Sep 2025. URL: https://doi.org/10.3389/fimmu.2025.1650852, doi:10.3389/fimmu.2025.1650852. This article has 2 citations and is from a peer-reviewed journal.
(armanitourret2024immunetargetingof pages 16-18): Marie Armani-Tourret, Benjamin Bone, Toong Seng Tan, Weiwei Sun, Maxime Bellefroid, Tine Struyve, Michael Louella, Xu G. Yu, and Mathias Lichterfeld. Immune targeting of hiv-1 reservoir cells: a path to elimination strategies and cure. Nature reviews. Microbiology, 22:328-344, Feb 2024. URL: https://doi.org/10.1038/s41579-024-01010-8, doi:10.1038/s41579-024-01010-8. This article has 57 citations.
(holloway2024inhibitionofcaspase pages 1-2): Alex J. Holloway, Tais B. Saito, Kubra F. Naqvi, Matthew B. Huante, Xiuzhen Fan, Joshua G. Lisinicchia, Benjamin B. Gelman, Janice J. Endsley, and Mark A. Endsley. Inhibition of caspase pathways limits cd4+ t cell loss and restores host anti-retroviral function in hiv-1 infected humanized mice with augmented lymphoid tissue. Retrovirology, May 2024. URL: https://doi.org/10.1186/s12977-024-00641-2, doi:10.1186/s12977-024-00641-2. This article has 2 citations and is from a peer-reviewed journal.
(mohammadzadeh2025hivpersistencein pages 37-43): N Mohammadzadeh. Hiv persistence in the brain despite effective antiretroviral therapy, implications for brain innate immune response and treatment. Unknown journal, 2025.
(yildirir2024smacmimeticssensitize pages 191-196): B Molyer Yildirir. Smac mimetics sensitize hiv-infected cells to mg1-mediated death. Unknown journal, 2024.
(calado2024decipheringthemechanisms pages 199-203): AM Calado. Deciphering the mechanisms underlying the colonization and spread of hiv in the central nervous system and the pathogenesis of hiv-associated neurological …. Unknown journal, 2024.
(armanitourret2024immunetargetingof pages 20-22): Marie Armani-Tourret, Benjamin Bone, Toong Seng Tan, Weiwei Sun, Maxime Bellefroid, Tine Struyve, Michael Louella, Xu G. Yu, and Mathias Lichterfeld. Immune targeting of hiv-1 reservoir cells: a path to elimination strategies and cure. Nature reviews. Microbiology, 22:328-344, Feb 2024. URL: https://doi.org/10.1038/s41579-024-01010-8, doi:10.1038/s41579-024-01010-8. This article has 57 citations.
(castillo2024myeloidcellreservoirs pages 9-10): Amber A. Castillo, Corbin McElrath, Grace Marshall, and Mario Stevenson. Myeloid cell reservoirs: role in hiv-host interplay and strategies for myeloid reservoir elimination. Current Clinical Microbiology Reports, 11:209-219, Aug 2024. URL: https://doi.org/10.1007/s40588-024-00234-9, doi:10.1007/s40588-024-00234-9. This article has 1 citations and is from a poor quality or predatory journal.