HIV 9/5/25

Vocabulary flashcards covering key HIV/AIDS concepts, pathogens, diagnostics, treatments, prophylaxis, and clinical stages from the lecture notes.

HIV

Human immunodeficiency virus; retrovirus that infects CD4 T-cells via gp120 and CD4 receptor, CCR5 coreceptor leading to immune deficiency.

HIV1 is human only, spread thru sexual (direct) contact and body fluids

testing for HIV

• ELISA: Look for antigen p24. Detected earlier than antibodies. Antibody test can take 23 to 90 days to detect after exposure

• If p24 neg, HIV-neg

• If p24-pos : Immunoassay HIV-1 or HIV-2

• If neg/maybe : Nucleic acid testing (RNA)

old test was western blot, not really used anymore

HIV resistance mechanisms

• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Bind to reverse transcriptase. Single mutations often enough. K103N: resistance to efavirenz, nevirapine. Y181C, G190A: resistance to multiple NNRTIs.

• Fusion inhibitors (e.g., enfuvirtide) : Mutations in gp41 protein prevent drug binding

PrEP details

Emtricitabine/tenofovir (FTC/TDF): Truvada

• Both reverse transcriptase inhibitors (NRTIs)

Injectable PrEP: Cabotegravir (CAB-LA)

Long-acting integrase inhibitor

IM injection every 2 months

• Highly effective, good for adherence challenges

Risk reduction?

• Sexual activity 99%

• IV drug use ≥74%

Maximal protection achieved?

• Receptive anal intercourse: 7 days daily use protection

• Receptive vaginal intercourse: 21 days daily use protection

• On-demand / Event-based (“2-1-1”) regimen

• Validated only MSM

• 2 pills taken 2–24 hours before sexual intercourse

• 1 pill 24 hours later, and 1 pill 48 hours later

medication to know

Emtricitabine/tenofovir (FTC/TDF): Truvada : reverse transcriptase inhibitors (NRTIs)

Cabotegravir CAB-LA: injectable prep. long acting integrase inhibitor

Pre exposure prophylaxis (PrEP) for HIV

• Daily or event-based use of antiretroviral drugs by HIV-negative individuals to prevent infection

—Maintains drug levels in blood and mucosal tissues

—Blocking HIV replication at earliest stage of exposure

• High-risk groups include: MSM with no condom use, Receptive anal intercourse with no condom use, Heterosexual individuals with HIV-positive partners or multiple partners, Serodiscordant couples (one partner HIV-positive, one negative), Individuals with recent sexually transmitted infections (STIs), People who inject drugs

• Preventive, not lifelong: started and stopped based on risk

• Always pair with other prevention strategies

• Effectiveness depends heavily on adherence

• Every 3 months: HIV test, STI screening, adherence check

— If HIV positive, stop (resistance), other treatment regimen

pt monitoring/followup testing

Viral load, monitored: As clinical “latency” established, baseline levels

indicate likelihood of progression to AIDS

CD4 levels, monitored

• When to indicate prophylaxis

• CrAg testing

• Look out for opportunistic infections,

malignancies

Genotype/phenotype of virus over time : May detect drug resistance

goals of ART/HAART (highly active antiretroviral therapy)

• Reduction in HIV morbidity and mortality

• Reduction of plasma viral RNA load

• Prevent transmission to others (sexual partners, mother to infant, needle-sharing)

• Manage and reduce HIV drug resistance →mutates rapidly, no “drug holidays”

• Improve overall immune function

• Improve quality of life for those with HIV/AIDS

immune reconstitution inflammatory syndrome (IRIS)

Mechanism

• Exaggerated immune response following ART initiation, unmasking or worsening subclinical infections or inflammatory conditions

• Instead of a measured response, immune system overreacts, leading to tissue-damaging inflammation

• Cytokine release (especially IFN-γ, TNF-α, IL-6) contributes to clinical deterioration

Presentation: Worsening symptoms (from infection/s) shortly after ART initiation, even in the absence of new infection

Typically occurs within weeks to 3 months of starting ART

The lower the CD4 level and the higher the HIV viral load, the higher the chance of IRIS!

rapid antigen/antibody test

18-90 days after exposure/infection

antibody test

23-90 days after exposure/infection

stages of HIVAIDS

Primary infection: Can be no signs/symptoms for the first 2-4 weeks

Acute HIV syndrome

• Mononucleosis-like symptoms: fever, night sweats, malaise, sore throat, rash, lymphadenopathy, GI upset, myalgias

• Coincides with spike in viral RNA in the blood as viruses are being produced, and drop in CD4 #

Clinical latency

• No signs and symptoms

• Virus may still be produced, at lower levels; could be non-infectious

• Patient can remain here for years

• The viral load remaining after the patient exits the acute stage indicates the probability they will progress to AIDS, and “how fast”

AIDS-Related complex

• As CD4 numbers drop below 500 cells/uL

• Generalized lymphadenopathy, fever, weight loss

Acquired immune deficiency syndrome (AIDS) / HIV Stage 3

• CD4 drop below 200 cells/uL

clinical HIV latency

• Variable progression from initial infection through latency to AIDS

• Some will stay in latency (infectious) for 10-15 years - detectable virus. Little if any symptoms and not on medications, potentially unaware of infection

• Asymptomatic, infected but NOT on HIV medications, virus detectable. Can still transmit. 15% OF INDIVIDUALS WITH HIV DO NOT KNOW THEY HAVE IT!

• Undetectable. On HIV medications, virus is undetectable in lab studies. If someone is undetectable, cannot transmit HIV to sexual partner

HIV risk factors

• Unprotected sex, inadequate education on safe sex practices

• Anal sex is riskiest for HIV

• Multiple sexual partners

• Male–male sex; especially those who are Black/African American and Hispanic/Latino, have high rates of new HIV diagnoses

• Having an STI • Sharing contaminated needles, syringes

• Accidental needlestick injury

• <1%, but still a possibility

• Receiving unsafe injections, blood transfusions and tissue transplantation, and medical procedures that involve unsterile cutting or piercing

• Engaging in use of alcohol and drugs in context of sexual behaviour

• Access to PrEP, ART

AIDS/HIV stage 3

• CD4 levels drop below 200 cells/uL

• AIDS-defining conditions

• Opportunistic infections

—”Cut-offs” = CD4 #

—Some have prophylaxis

• Malignancies

• Wasting syndrome

—Loss of lean body mass

opportunistic infection to screen for at any CD4 count of HIV+ ppl

Mycobacterium tuberculosis

• Reactivation, dissemination

opportunistic infection to screen for at <200 CD4 cells/uL

• Pneumocystis jivorecii (PCP) – monomorphic fungus –pneumonia — Prophylaxis: Trimethoprim-sulfamethoxazole (TMP-SMX) (bactrim)

• Coccidioides immitis - dimorphic fungus, pneumonia, disseminated infection, endemic to Arizona, California

• Human Herpes Virus 8 (HHV8) – Enveloped dsDNA virus — Highly vascular skin/mucus membrane neoplasia (Kaposi’s sarcoma)

• Cryptosporidium parvum, – protozoan, profuse watery diarrhea, chronic

• Candida albicans –Yeast; oral thrush. Prophylaxis NOT warranted (resistance outweighs)

• Herpes simplex virus – Enveloped dsDNA virus; reactivation — Oral or genital lesions, encephalitis, keratitis, esophagitis

opportunistic infection to screen for at <100 CD4 cells/uL

• Toxoplasma gondii – protozoan, reactivation in CNS (encephalitis, abscesses) — Prophylaxis: Trimethoprim-sulfamethoxazole (TMP-SMX)

• Cryptococcus neoformans – monomorphic yeast, encapsulated, meningitis

• Histoplasma capsulatum – dimorphic yeast, disseminated infection, endemic to Ohio/Mississippi River valleys — Prophylaxis – Itraconazole

• Candida albicans –Yeast; esophagitis

• JC Virus – DNA virus, reactivation; Progressive Multifocal Leukoencephalopathy (PML)

opportunistic infection to screen for at <50 CD4 cells/uL

• Mycobacterium avium complex (MAC): Disseminated infections, multiple body sites. “Non-specific systemic symptoms.” One of the most common opportunistic infections in AIDS patients in the US — Prophylaxis: Azithromycin

• Cytomegalovirus – Enveloped dsDNA virus; reactivation — Esophagitis, retinitis, colitis, pneumonia

Cryptococcus screening in HIV

• Cryptococcus neoformans and Cryptococcus gatti: Encapsulated yeast. Bird droppings, soil around trees. Inhalation. 152,000 cases of cryptococcal meningitis/meningoencephalitis occur among people living with HIV worldwide. 112,000 deaths occur, majority in sub-Saharan Africa

• Cryptococcal antigen (CrAg) : Detectable in blood before development of meningitis

• Recommended in HIV patients with CD4 <100

• Considered in HIV patients with CD4 <200

• Preemptive fluconazole therapy: ~25% fail, going on to develop disease or die

next steps if CrAg negative

• No antifungal therapy

• Proceed with ART

next steps if CrAg positive but asymptomatic

• Start preemptive fluconazole therapy

• Delay ART initiation for 2–4 weeks to reduce risk of

immune reconstitution inflammatory syndrome (IRIS)

next steps if CrAg positive and symptomatic

• Evaluate with CSF testing

• If cryptococcal meningitis: antifungal induction therapy

• Amphotericin B + flucytosine if available, or high-dose fluconazole

pediatric HIV

Acquired at time of birth (perinatal)

• Management infected mother: appropriate screening, pre-exposure prophylaxis (PrEP), ART

• Zidovudine give IV to mother just prior to delivery (if viral load is >1,000 copies/mL). If viral load is >1,000 copies/mL, may also deliver by cesarian

• Breastfeeding – educate against if virus detected

At birth, infants (if mother HIV-pos) will be given HIV antivirals for the first 2-6 weeks

• PCR of infant can help determine if HIV-neg/-pos

• 50% of children born with HIV die before 2 years of age without treatment

Pediatric HIV

• Slow growth, poor weight gain; severe wasting; persistent diarrhea; opportunistic infections

• Pneumocystis pneumonia = one-half of all AIDS-defining conditions diagnosed during the first year of life

• HIV encephalopathy

federally reportable infection

hiv and aids at any stage

any opportunistic inf as result of hiv inf

Retroviridae

Virus family to which HIV belongs; 2 copies of linear, positive sense enveloped ssRNA with reverse transcription and genome integration.

gp120

HIV envelope protein that binds the CD4 receptor to initiate entry into the host cell.

gp41

HIV envelope protein that mediates fusion of viral and host cell membranes.

CD4 T-cell

Helper T cell targeted by HIV; depletion leads to immunodeficiency and AIDS.

CCR5 coreceptor

Chemokine receptor used by many HIV strains for entry; target of CCR5 antagonists.

CXCR4 coreceptor

Chemokine receptor used by X4-tropic HIV for entry; associated with disease progression.

HIV-1

Most common HIV type worldwide; primarily human-to-human transmission.

HIV-2

HIV type largely confined to West Africa; slower progression and different drug susceptibility. zoonotic

HIV replication strategy

• Virus binds via gp120 and fuses with host cell (CD4 T-cell #1) — CD4 receptor — CXCR4 or CCR5 can be coreceptors

• Fusion aided by viral surface protein gp41

• Uncoated, and release of viral proteins including reverse transcriptase and integrase

• Reverse transcriptase converts viral RNA to DNA

• Inside the cell’s nucleus, the new viral DNA is integrated into the host DNA → viral integrase — RNA virus that replicates in nucleus

• Integrated viral DNA is transcribed by host cell to make new HIV RNA and translated into HIV proteins

• HIV RNA and proteins move to the cell surface, assembled • Viruses exit cell and released by protease — Cleaves to release mature HIV viruses = infect next cell or host

gp120–CD4 binding

Initial attachment step where HIV binds CD4, enabling entry.

NRTI

Have nucleoside structurally similar to T-cell DNA nucleoside, this mimicry enabling NRTA to integrate with T-call DNA to stop production of viral DNA proteins

Backbone of ART - usually 2 drug combo

NNRTI

Bind directly to the HIV’s reverse transcriptase enzyme and inhibit its activity.

PI

Block protease needed produce infectious HIV particle

INSTI

Integrase strand transfer inhibitors; inhibit integrase necessary for HIV to insert its viral DNA into the CD4 cell DNA for replication.

HIV immune suppression strategies

• Proteins (e.g., Vpu, Vif, Nef) interfere with normal intracellular pattern-recognition receptors, such as RIG-1 — Reduces/stops interferon (IFN) production

• Blocks activation of transcription factors responsible for IFN production

• Rapid mutation and high variability — Reverse transcriptase is error-prone — Escape mutants that evade CD8 and neutralizing antibodies

• HIV Nef protein reduces MHC-I on infected cells

• Killing of infected CD4 T-cells

Drug targets that prevent binding

CCR5 antagonists

Post-attachment inhibitors

Attachment inhibitors

Fusion inhibitor

Block the fusion of the HIV envelope and CD4 cell membrane preventing entry of HIV into the CD4 cell

CCR5 antagonist

Blocks CCR5 coreceptor needed in addition to the CD4 receptor for binding to the CD4 surface.

Attachment inhibitor

Bind to the gp120 protein on the outer surface of HIV, preventing HIV from entering CD4 cells.

Post-attachment inhibitor

Block CD4 receptors on the surface cell surfaces that HIV needs to enter the cells.

HIV-1 vs HIV-2 difference

HIV-1 is more prevalent and aggressive; HIV-2 slower progression and distinct drug susceptibility.

Epidemiology, transmission

• HIV-1: most common worldwide (>95% of cases)

• HIV-2: largely confined to West Africa and areas with migration links (Portugal, India)

Disease progression

• HIV-1: more aggressive; faster progression to AIDS if untreated

• HIV-2: slower progression, lower viral loads, and “less infectious”

Treatment

• HIV-2 intrinsically resistant to some first-line HIV drugs : Non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g., efavirenz, nevirapine), Some fusion inhibitors

what happens when cd4 t cells are depleted?

Loss of immune coordination

• Impairs activation of CD8 T-cells →Reduced ability to kill virus-infected cells

• Impairs activation of B-cells → Poor antibody production and affinity maturation

Impaired host defense against pathogens … as CD4 level drops, more likely

• Loss of signaling weakens macrophage and neutrophil function

• Opportunistic infections (bacterial, viral, fungal, parasitic)

Failure of tumor surveillance →Malignancies

Chronic inflammation →T-cell exhaustion, apoptosis, further immune collapse

p24

HIV capsid protein; detectable early and used in some diagnostic tests.

NAT (Nucleic Acid Test)

Test that detects HIV RNA/DNA; earliest marker of infection during acute HIV. 10-33 days after exposure/infection

Antigen/Antibody test (4th-gen ELISA)

Screening test detecting HIV antibodies and p24 antigen; faster detection than antibodies alone. 18-45 days after exposure/infection

Western Blot

Traditional confirmatory HIV antibody test; now largely supplanted by 4th-gen algorithms.

Seroconversion window period

Time after exposure before HIV antibodies are detectable; RNA/p24 may be detectable earlier.

CrAg screening

Cryptococcal antigen screening in HIV patients with low CD4 to detect cryptococcal meningitis risk.

Cryptococcus neoformans

Encapsulated yeast causing meningitis in AIDS; CrAg positive in serum/CSF.

Pneumocystis jirovecii pneumonia (PCP)

Opportunistic pneumonia; common when CD4 <200; prophylaxis with TMP-SMX.

MAC (Mycobacterium avium complex)

Disseminated mycobacterial infection, often CD4 <50; prophylaxis considerations.

Toxoplasma gondii

Protozoan causing encephalitis in AIDS; prophylaxis considered with IgG positivity and low CD4.

Coccidioidomycosis

Fungal pneumonia; endemic to the Southwest US; possible opportunistic infection.

Cryptosporidium parvum

Protozoan causing profuse watery diarrhea in AIDS; often chronic.

Cytomegalovirus (CMV)

DNA virus causing retinitis, esophagitis, colitis in advanced AIDS.

JC virus

Polyomavirus causing Progressive Multifocal Leukoencephalopathy (PML) in AIDS.

HHV-8 (Kaposi’s sarcoma virus)

Herpesvirus causing Kaposi’s sarcoma, an AIDS-defining malignancy.

Candida albicans

Yeast causing oral thrush and esophagitis in HIV/AIDS.

HIV encephalopathy

HIV-associated neurocognitive disorder; brain dysfunction related to infection.

Wasting syndrome

Unintentional weight loss with chronic diarrhea and weakness in AIDS.

IRIS

Immune Reconstitution Inflammatory Syndrome; paradoxical inflammation after ART initiation.

AIDS-defining illnesses

Opportunistic infections and cancers that define progression to AIDS when CD4 declines.

Prophylaxis

Preventive treatment to avert opportunistic infections in HIV, based on CD4 counts.

TMP-SMX

Trimethoprim-sulfamethoxazole; first-line prophylaxis for PCP and often used for MAC risk.

Azithromycin

Prophylaxis against MAC when CD4 is very low (often <50 cells/µL) or high risk.

Itraconazole

Antifungal prophylaxis for Histoplasma in endemic regions; used in AIDS prophylaxis scenarios.

Fluconazole

Antifungal used for cryptococcal screening management (preemptive) and treatment of fungal infections.

Histoplasma capsulatum

Dimorphic fungus; can cause disseminated disease in AIDS; prophylaxis in certain regions.

Cryptosporidiosis

Cryptosporidium infection causing severe diarrhea in AIDS; often persistent.

PML (Progressive Multifocal Leukoencephalopathy)

Demyelinating disease caused by JC virus reactivation in advanced HIV.

Serodiscordant

Couple in which one partner is HIV-positive and the other is HIV-negative.

Serology window period testing

Concept related to timing of HIV antibody and antigen tests after exposure.

Perinatal HIV transmission

Mother-to-child transmission; management includes maternal ART and infant prophylaxis.

Pediatric HIV management

HIV acquired perinatally; ART and perinatal prophylaxis reduce infant mortality.

ART goals

Reduce HIV morbidity/mortality, lower plasma RNA, prevent transmission, maintain immune function.

IRIS timing risk

IRIS more likely when CD4 is very low and viral load is high at ART initiation.