HIV/AIDS

Vocabulary flashcards covering key terms and definitions related to HIV/AIDS from the lecture notes.

Federal Reporting

HIV or AIDS at any stage

any opportunistic infection resulting from HIV infection

Retroviridae characteristics

enveloped

positive ssRNA

linear

2 copies of RNA

has viral enzymes to convert its RNA into DNA

Retroviridae cell infection

infects CD4 T cells

uses gp120, CD4 receptor, and CCR5 coreceptor

HIV viral family

retroviridae

HIV reservoir

HIV1- human only

HIV2- zoonotic

HIV transmission

body fluids (blood, semen, vaginal secretions, breast milk)

direct contact (sexual contact, blood transfusion, needlestick)

HIV epidemiology

millions infected in 1990

now less than 1 million infected worldwide

HIV sexual risk factors

unprotected sex (especially anal)

multiple partners

male-male sex

having STI

alcohol and drug use during sex

HIV needle risk factors

sharing needles

receiving unsafe injections

accidental needlestick

Greatest HIV prevalence

sub-saharan africa

HIV prevalence by age

13-24 reduction of new infections

25-34 years highest rate of new diagnosis

55-64 years has most people living with HIV

HIV replication: binding

binds CD4 receptor on CD4 T cell

uses gp120, CCR5, and CSCR4 to bind

HIV replication: fusion

fuses with host cell using surface protein gp41

HIV replication: reverse transcription

reverse transcriptase converts viral RNA to DNA in the cytoplasm

HIV replication: integration and replication

integrase inserts viral DNA into host DNA →

replicates in nucleus

HIV replication: exit

new virus buds to exit, and uses protease to fully cleave

HIV replication steps

binding and fusion

reverse transcription

integration and replication

assembly

budding/exit

HIV immune suppression

proteins interfere with normal immune strategies

blocks transcription factors for interferon production

rapid mutation and high variability

kills infected CD4 T cells

Viral Load & CD4: acute HIV syndrome

viral DNA- exponential increase

CD4- sharp decrease

Viral Load & CD4: latency

viral DNA- sharp decrease initially, then slowly rises through latency

CD4- small increase initially, then progressive decline

Viral Load & CD4: AIDS complex

viral DNA- slowly increases, then exponential increase

CD4- slow and progressive decrease

Results of CD4 depletion

loss of immune coordination

impaired defense against pathogens

malignancies

chronic inflammation

CD4 depletion causing loss of immune coordination

impairs CD8 t cells, leading to reduced ability to kill virally infected cells

impairs b cell activation

CD4 depletion causing impaired immune defenses

increases occurrence of opportunistic infections

CTL

cytotoxic T cells; responsible for infection control

Antibody Response: CTL

increase during initial infection

level out during latency

decreased before death

ENV

HIV envelope; would neutralize from new infection

Antibody Response: ENV

increase a lot during initial infection

level out during latency

slightly decrease before death

p24

HIV capsid protein; part of HIV diagnosis; present before antibodies

Antibody Response: p24

slight increase during initial infection

level out to a low level during latency

decrease during AIDS stage

Primary infection

no signs or symptoms for the first 2-4 weeks

virus being made, still infectious

Acute HIV syndrome

lymphadenopathy

non-specific mononucleosis-like symptoms

spike in viral RNA and drop in CD4

Viral load after acute stage

indicates probability of progressing to AIDS and the speed

Clinical Latency

result of CD8

no signs and symptoms, possibly non-infectious

variable progression, can last 10-15 years

Clinical Latency: Asymptomatic & Not Medicated

virus detectable

can transmit

15% don’t know HIV+

Clinical Latency: Undetectable

on medication

not detectable in lab studies

cannot transmit

AIDS-related complex

CD4 below 500 cells/uL

generalized lympadenopathy, fever, weight loss

AIDS

CD4 below 200 cells/uL

HIV stage 3

defining condition

gp120

HIV envelope glycoprotein

binds the CD4 receptor to initiate entry

gp41

HIV transmembrane glycoprotein

mediates fusion of the viral envelope with the host cell membrane

CCR5

Coreceptor used by HIV for entry

CXCR4

Coreceptor used by HIV for entry

Reverse transcription

Enzymatic process that converts viral RNA into DNA

Integrase

Viral enzyme that inserts HIV DNA into the host genome

Protease

Viral enzyme that processes viral polyproteins into mature, infectious HIV particles

Patient Monitoring

monitor viral loads

monitor CD4 levels

test for genotype and phenotype of virus periodically to detect drug resistance

HIV Care Retention

only 50% retained care

Reasons for Poor Retention

unmet socioeconomic needs

limited financial resources

scheduling

medication burnout

substance use disorder

mental health

IRIS Mechanism

exaggerated/overreactive immune response after starting ART

unmasks or worsens subclinical infections/inflammatory conditions

IRIS Presentation

worsening symptoms from infections after starting ART

usually occurs weeks to 3 months after starting ART

IRIS Risk

increased IRIS risk with low CD4 and high viral load

Immune Reconstitution Inflammatory Syndrome

NRTI

nucleoside reverse transcriptase inhibitors

NRTI action

has nucleotide similar to T Cell DNA

mimicry enables integration of nucleotide in T Cell DNA

stops production of viral DNA proteins

NNRTI

non-nucleoside reverse transcriptase inhibitor

PI

protease inhibitor

INSTI

integrase strand transfer inhibitors

Backbone of ART

NRTIs

TDF/TAF and FTC

Fusion Inhibitor Action

causes gp41 mutations, which prevents binding

NNRTI Action

bind reverse transcriptase and signal mutations

Mutations in Drug Targets

reverse transcriptase is error-prone

HIV has high mutation rate

HIV Drug Treatment Classes

NRTIs

NNRTIs

PIs

INSTIs

entry inhibitors

Pre-exposure prophylaxis

HIV-negative individuals take antiretrovirals to prevent infection

paired with other prevention strategies

High Risk HIV Groups

male to male sex with no condom

receptive anal intercourse with no condom

IVDU

Truvada

FTC/TDF

reverse transcriptase inhibitors

Cabotegravir

injectable PrEP (every 2 months)

CAB-LA

long acting integrase inhibitor

window period: nucleic acid testing

10-33 days after exposure

window period: antigen/antibody lab test

18-45 days after exposure

window period: rapid antigen/antibody test

18-90 days after exposure

window period: antibody test

23-90 days after exposure

ELISA

screening assay for p24 antigen

detected early that antibodies

p24 negative

HIV negative

no further testing

p24 positive

immunoassay to determine HIV1 or HIV2

p24 negative/maybe

nucleic acid testing

Western blot

older method for confirming HIV

HIV-1 vs HIV-2 Epidemiology

HIV1- most common

HIV2- confined to West Africa

HIV-1 vs HIV-2 Disease Progression

HIV1- more aggressive, faster progression to AIDS if untreated

HIV2- slower progression, lower viral loads, less infectious

HIV-1 vs HIV-2 Treatment

HIV 2 resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some fusion inhibitors

CrAg negative steps

no antifungal therapy

continue ART

CrAg positive and asymptomatic

start preemptive fluconazole therapy

delay ART initiation 2-4 weeks to reduce chance of IRIS

CrAg positive and symptomatic

evaluate with CSF

treat with amphotericin b AND flucytosone (can also use high dose fluconazole)

Cryptococcus screening

recommended if CD4 less than 100

yeast transmitted in bird droppings or soil

Cryptococcal antigen

used to screen HIV patients with low CD4 for cryptococcus

detection in blood precedes meningitis

Cryptococcus neoformans

Encapsulated yeast

causes cryptococcal meningitis

Opportunistic infections: less than 200 CD4

Pneumocystis jirovecii pneumonia

coccidiodes immitis

HHV8

crytptosporidium parvum

candida albicans (thrush)

HSV

Opportunistic infections: less than 100 CD4

toxoplasma gondii

cryptococcus neoformans

histoplasma capsulatum

candida albicans (esophagitis)

jc virus

Opportunistic infections: less than 50 CD4

mycobacterium avium complex (MAC)

cytomegalovirus

HSV

can be reactivated

causes oral or genital lesions, encephalitis, keratitis, or esophagitis

Pneumocystis jirovecii pneumonia

PCP; yeast; prophylaxis with Bactrim

Mycobacterium avium complex

disseminated infection

non-specific systemic symptoms

most common opportunistic AIDS

prophylaxis is azithromycin

Cytomegalovirus

reactivation of latent herpesviridae infection

causes esophagitis, retinitis, colitis, pneumonia

Toxoplasma gondii

protozoan transmitted via cat feces and undercooked meat

reactivation in CNS causing encephalitis or abscesses

prophylaxis is bactrim

Cryptosporidium parvum

Protozoan

causes profuse watery diarrhea in AIDS

often seen with severe CD4 depletion

no prophylaxis

Histoplasma capsulatum

Dimorphic fungus causing disseminated infection

endemic to Ohio & Mississippi River Valleys

prophylaxis is itraconazole

Coccidioides immitis

Dimorphic fungus causing pneumonia/dissemination

endemic in Arizona and California

no prophylaxis

Mycobacterium tuberculosis

reactivation and dissemination risk increased in HIV

screen regardless

Candidiasis (oropharyngeal thrush)

White plaques on oral mucosa or tongue that may be scraped off

no prophylaxis

HHV8

Kaposi’s Sarcoma; skin/mucosal neoplasia

JC virus

Progressive multifocal leukoencephalopathy

reactivation of infection in the brain

AIDS Defining Neoplasms

Non-Hodgkin’s lymphoma

HIV encephalopathy

kaposi’s sarcoma

cervical cancer

Non-Hodgkin’s Lymphoma

primary lymphoma of the brain; other subtypes