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HIV antiretroviral therapy guidelines treatment

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HIV - Etiology, Pathology, Clinical Features, Differential Diagnosis, Investigations, Management & Long-Term Implications

1. Etiology

The Pathogen

HIV (Human Immunodeficiency Virus) is a lentivirus belonging to the family Retroviridae. It exists as two types:

HIV-1: The dominant global strain, responsible for the pandemic
HIV-2: Less virulent, largely confined to West Africa, lower transmissibility, slower progression

HIV-1 originated from cross-species transmission of simian immunodeficiency virus (SIV) from chimpanzees to humans in sub-Saharan Africa, likely early 20th century.

Virion Structure

Fig. 6.38 The HIV-1 virion - Robbins & Kumar Pathologic Basis of Disease

The HIV-1 virion is spherical (~100 nm diameter) with a cone-shaped core, containing:

p24 capsid (the most abundant antigen, target for ELISA diagnosis)
Two copies of single-stranded RNA
Three key enzymes: reverse transcriptase, protease, integrase
p17 matrix protein beneath the envelope
Envelope glycoproteins gp120 and gp41 - critical for cell entry

The RNA genome contains standard retroviral genes (gag, pol, env) plus accessory genes (tat, rev, vif, nef, vpr, vpu). The tat gene product causes a 1000-fold increase in transcription of viral genes.

Transmission

HIV is transmitted via:

Sexual contact (most common globally) - anal intercourse carries highest risk per act
Blood/blood products - sharing needles, transfusions, needle-stick injuries
Mother to child - transplacental, intrapartum, or breastfeeding (perinatal transmission)

The virus is not transmitted by casual contact, insect bites, or shared utensils.

2. Pathology (Pathogenesis)

Cell Entry

HIV uses CD4 as its primary receptor. This explains its selective tropism for:

CD4+ T helper cells (primary target)
Macrophages and dendritic cells (low-level CD4 expression)

After binding CD4, gp120 undergoes conformational change and binds a coreceptor - either CCR5 (on macrophages, early in infection) or CXCR4 (on T cells, late in infection). Individuals homozygous for a 32-bp deletion in CCR5 (CCR5Δ32) are highly resistant to HIV infection.

Replication Cycle

gp120 binds CD4 + CCR5/CXCR4 → membrane fusion via gp41
Viral core enters cytoplasm
Reverse transcriptase converts viral RNA → double-stranded DNA (prone to errors = high mutation rate)
Integrase inserts proviral DNA into host genome
Viral proteins assembled and budded as new virions (cleaved by protease)

Immune Destruction

Mechanisms of CD4+ T cell depletion:

Direct cytopathic effect of viral replication
Apoptosis of infected and uninfected bystander T cells
CD8+ CTL-mediated killing of infected cells
Chronic immune activation and exhaustion
Formation of syncytia (giant multinucleated cells)

The selective depletion of CD4+ T cells - which orchestrate virtually the entire adaptive immune response - explains the catastrophic immune failure of AIDS. Loss of CD4+ T-cell help means CD8+ T cells and B cells also fail progressively.

HIV reservoirs: The virus establishes latent infection in resting memory CD4+ T cells, where proviral DNA persists indefinitely, invisible to CTLs. This reservoir is the central barrier to cure.

3. Clinical Features / Natural History

Natural history of HIV infection showing CD4 count declining over years and viral load rising at AIDS stage

Fig. 6.42 Clinical course of HIV infection (Robbins & Kumar Pathologic Basis of Disease)

Phase 1: Acute Retroviral Syndrome (Weeks 2-4)

Occurs in 40-90% of newly infected individuals. Presents as a mononucleosis/flu-like illness:

Symptom	Frequency
Fever	Very common
Lymphadenopathy (axillary, cervical, occipital)	Common
Pharyngitis	Common
Maculopapular rash (5-10 mm lesions)	Common, 48-72 h after fever onset
Myalgia/arthralgia	Common
Diarrhea, anorexia, weight loss	Common
Retroorbital headache	Frequently reported
Painful mucocutaneous ulcers	Distinctive

At this stage, viremia is extremely high (up to 10^7 copies/mL) and the CD4 count drops sharply. Resolves spontaneously in 2-4 weeks.

Phase 2: Clinical Latency (Years 1-10)

CD4 count gradually declines from ~1000 cells/mm³ toward 200
Viral replication continues in lymphoid tissues despite apparent clinical wellness
Persistent generalized lymphadenopathy may persist
Without ART, median time to AIDS is ~10 years
"Elite controllers" (~0.3%) maintain viral suppression without ART

Phase 3: AIDS (CD4 < 200 cells/mm³ or AIDS-defining illness)

Constitutional symptoms: Fever, night sweats, weight loss (>10% body weight), chronic diarrhea - the "wasting syndrome"

Opportunistic infections by CD4 count threshold:

CD4 (cells/mm³)	Opportunistic Infections
< 500	Oral candidiasis, herpes zoster, bacterial infections
< 200	Pneumocystis jirovecii pneumonia (PCP) - most common life-threatening OI in developed countries
< 100	Toxoplasmosis (cerebral), Cryptococcal meningitis
< 50	CMV retinitis/colitis, Mycobacterium avium complex (MAC), CNS lymphoma

Specific notable infections:

PCP: Subacute onset dyspnea, dry cough, low-grade fever; bilateral interstitial infiltrates on CXR; "ground-glass" on CT; elevated LDH
Cerebral toxoplasmosis: Multiple ring-enhancing lesions on CT/MRI, usually bilateral
Cryptococcal meningitis: Insidious headache, altered consciousness; Indian ink stain of CSF; cryptococcal antigen positive
CMV retinitis: "Pizza pie" fundal appearance; risk of blindness
MAC: Disseminated; fever, night sweats, weight loss, anemia, elevated alkaline phosphatase
Persistent diarrhea: Cryptosporidium, Cystoisospora belli, microsporidia
Esophageal candidiasis: Odynophagia; AIDS-defining

AIDS-defining malignancies:

Kaposi Sarcoma (KS): Most common AIDS-associated neoplasm. Caused by HHV-8. Violaceous skin/mucous membrane/GI lesions. Spindle cell proliferation of vascular origin. Widespread in AIDS (vs. sporadic localized form in elderly Mediterranean men).
B-cell lymphomas (including primary CNS lymphoma - EBV driven; and Burkitt's lymphoma)
Invasive cervical cancer (HPV-driven)
Anal carcinoma (HPV-driven)

CNS manifestations:

HIV encephalopathy/HIV-associated dementia: cognitive decline, motor dysfunction, behavioral changes
Vacuolar myelopathy
Peripheral neuropathy (sensory > motor)
Progressive multifocal leukoencephalopathy (PML) - JC virus reactivation

4. Differential Diagnosis

Acute HIV Syndrome - DDx:

Condition	Distinguishing Features
Infectious mononucleosis (EBV)	Tonsillar exudate, splenomegaly, heterophile antibodies
Toxoplasmosis	Lymphadenopathy, cat exposure; less pharyngitis
Rubella	Post-auricular nodes, prodromal rash pattern
Secondary syphilis	Palmoplantar rash, condyloma lata; RPR positive
Viral hepatitis	Jaundice, elevated transaminases prominently
Disseminated gonococcal infection	Migratory arthritis, pustular rash on extremities

AIDS-related opportunistic infections - DDx per presentation:

Pulmonary infiltrates in immunocompromised: PCP vs. bacterial pneumonia vs. TB vs. CMV pneumonitis vs. Kaposi sarcoma
Ring-enhancing brain lesions: Toxoplasmosis (most common) vs. CNS lymphoma vs. TB abscess vs. PML
Meningitis in AIDS: Cryptococcal vs. bacterial vs. tuberculous vs. CMV vs. lymphomatous

5. Investigations

Diagnosis of HIV Infection

Testing algorithm (WHO/CDC):

4th generation combined Ag/Ab ELISA (detects HIV-1/2 antibodies AND p24 antigen) - preferred initial test
- Window period: ~18-45 days from infection
Confirmatory: HIV-1/HIV-2 differentiation immunoassay
If Ag/Ab positive but differentiation test indeterminate: HIV RNA viral load (NAT)

Window periods:

HIV RNA (NAT): detectable 10-15 days post-exposure
p24 antigen: ~18-20 days
Antibody: 3-6 weeks (most seroconvert by 12 weeks)

Monitoring Established HIV

Test	Purpose	Target/Significance
CD4+ T cell count	Immune status; guides prophylaxis	Normal >500; AIDS <200
HIV viral load (RNA copies/mL)	Treatment efficacy; infectivity	Goal: undetectable (<50 copies) on ART
CD4/CD8 ratio	Immune recovery	Normally >1
HIV drug resistance genotyping	Guide ART selection	At baseline and treatment failure
HIV tropism testing	Before CCR5 antagonist use	R5 vs. X4 vs. dual tropic

Other baseline investigations

FBC, LFTs, U&E, lipids, glucose, urinalysis (HIVAN screening)
Hepatitis B (HBsAg, anti-HBc, anti-HBs), Hepatitis C, syphilis serology
TB screening (TST/IGRA), chest X-ray
Toxoplasma IgG (if <100 CD4), Cryptococcal antigen (if <100 CD4 in endemic areas)
Cervical smear (women), STI screen
CMV IgG

6. Management

When to Start ART

All HIV-positive individuals should be offered ART regardless of CD4 count - this is current universal guidance. Early treatment prevents immune damage, reduces transmission, and reduces non-AIDS morbidity (cardiovascular, renal, malignancy).

ART Drug Classes and Mechanisms

Class	Mechanism	Examples
NRTIs (Nucleoside Reverse Transcriptase Inhibitors)	Inhibit reverse transcription (chain termination)	Tenofovir (TDF/TAF), Emtricitabine (FTC), Lamivudine (3TC), Abacavir (ABC)
NNRTIs (Non-Nucleoside RT Inhibitors)	Non-competitive binding to reverse transcriptase	Efavirenz, Rilpivirine, Doravirine
PIs (Protease Inhibitors)	Block viral protease; prevent maturation	Darunavir, Atazanavir (boosted with ritonavir/cobicistat)
INSTIs (Integrase Strand Transfer Inhibitors)	Block proviral DNA integration	Dolutegravir, Bictegravir, Raltegravir
Entry inhibitors	Block gp41 (fusion) or CCR5	Enfuvirtide (fusion), Maraviroc (CCR5 antagonist)

Preferred First-Line Regimens (2024-2025 IAS-USA guidelines, PMID 39616604)

The standard of care is a 3-drug regimen (2 NRTIs + an INSTI):

Bictegravir/Tenofovir alafenamide/Emtricitabine (Biktarvy) - once daily, single pill - preferred
Dolutegravir + Tenofovir/Emtricitabine - alternative first-line
2-drug regimens: Dolutegravir + Lamivudine (for patients without HBV co-infection or high viral load)

The European AIDS Clinical Society (EACS) guidelines 2025 (PMID 41088922) maintain INSTIs as the backbone of first-line therapy.

Opportunistic Infection Prophylaxis

CD4 Count	Prophylaxis	Drug
< 200 cells/mm³	PCP	Trimethoprim-sulfamethoxazole (TMP-SMX) 1 DS tab daily
< 100 cells/mm³	Toxoplasmosis (if Toxo IgG+)	TMP-SMX (also covers PCP)
< 50 cells/mm³	MAC	Azithromycin weekly or clarithromycin daily

Prophylaxis can be discontinued once CD4 recovers above threshold on ART for >3-6 months.

Post-Exposure Prophylaxis (PEP)

Must begin within 72 hours of exposure
Regimen: Tenofovir-emtricitabine + Dolutegravir (or Raltegravir) for 28 days

Pre-Exposure Prophylaxis (PrEP)

Tenofovir-emtricitabine (Truvada) daily oral: >99% effective when adherent
Cabotegravir long-acting injectable (every 2 months): now preferred option in many guidelines

Management of AIDS-Defining Illnesses

PCP: TMP-SMX (high dose IV/oral) ± adjunctive corticosteroids if PaO₂ <70 mmHg
Cryptococcal meningitis: Amphotericin B + flucytosine (induction) → Fluconazole (consolidation/maintenance)
CMV retinitis: Ganciclovir/Valganciclovir
Toxoplasmosis: Pyrimethamine + sulfadiazine + folinic acid
MAC: Azithromycin or clarithromycin + ethambutol ± rifabutin
Kaposi Sarcoma: ART initiation alone often causes regression; liposomal doxorubicin for systemic disease

Immune Reconstitution Inflammatory Syndrome (IRIS): Paradoxical worsening of OIs when ART is started in severely immunosuppressed patients. Occurs 2-8 weeks after ART initiation. Management: NSAIDs, corticosteroids in severe cases; do not routinely stop ART.

7. Long-Term Implications

With Effective ART

Virologically suppressed patients on ART now have near-normal life expectancy. The focus has shifted to:

Cardiovascular disease: HIV causes chronic immune activation and inflammation, accelerating atherosclerosis. 2-fold increase in MI risk. Statins, lipid management, smoking cessation are key.
HIV-associated nephropathy (HIVAN): Collapsing FSGS in Black patients with high viral loads; ART is primary treatment; TDF-based regimens avoided in chronic kidney disease (switch to TAF or abacavir).
Metabolic complications: Lipodystrophy (fat redistribution - lipoatrophy + central fat accumulation), insulin resistance, dyslipidemia (especially with older PIs).
HIV-associated neurocognitive disorders (HAND): Range from asymptomatic neurocognitive impairment to HIV-associated dementia; viral reservoirs in CNS.
Liver disease: HIV/HCV co-infection accelerates fibrosis; HIV/HBV co-infection common (TDF/TAF-based regimens also treat HBV).
Bone disease: Osteopenia/osteoporosis (HIV and some ART drugs); DEXA screening recommended.
Non-AIDS-defining cancers: Increased risk of lung, liver, anal, oropharyngeal cancers.
Malignancy monitoring: Regular cervical smears, anal cytology in high-risk patients.

Psychosocial & Public Health

Stigma, depression, and mental health disorders are common and adversely affect adherence
U=U (Undetectable = Untransmittable): Virologically suppressed patients cannot sexually transmit HIV - a major prevention strategy
Prevention: Condom use, PrEP, harm reduction for PWID, PMTCT (preventing mother-to-child transmission) programs
No licensed vaccine exists as of 2026; broadly neutralizing antibody research ongoing

Sources:

Robbins, Cotran & Kumar Pathologic Basis of Disease - Chapter 6 (Immunodeficiency, HIV/AIDS), pp. 219-230
Goldman-Cecil Medicine - Chapters 354-357 (Pathobiology, Diagnosis, Prevention, Treatment of HIV)
IAS-USA Panel, Antiretroviral Drugs for Treatment and Prevention - JAMA 2025 (PMID 39616604)
EACS Guidelines v13.0, HIV Med 2026 (PMID 41088922)

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Mbbs level

Got it - MBBS level means clear, structured, exam-focused notes. No unnecessary complexity, but covers everything you need to know for finals/clinical exams.

HIV - Complete MBBS Notes

Lecture OG 27.3 | Medicine

1. ETIOLOGY

The Virus

HIV = Human Immunodeficiency Virus
Family: Retroviridae, Genus: Lentivirus
Two types: HIV-1 (global pandemic) and HIV-2 (West Africa, less virulent, slower progression)
Origin: Cross-species transmission from chimpanzees (SIV → HIV-1)

Structure (Know for MCQs)

Component	Function
gp120	Binds CD4 receptor on host cell
gp41	Mediates membrane fusion (entry)
p24 capsid	Most abundant antigen - used in diagnosis
p17 matrix	Structural; beneath lipid envelope
Reverse transcriptase	RNA → DNA (error-prone = high mutation rate)
Integrase	Inserts viral DNA into host genome
Protease	Cleaves precursor proteins → mature virion

Transmission Routes

Sexual (commonest globally) - unprotected sex; anal >> vaginal >> oral
Parenteral - sharing needles (IVDU), blood transfusion, needle-stick injury
Mother to child (MTCT) - transplacental, during delivery (most common), breastfeeding

NOT transmitted by: casual contact, coughing, sneezing, sharing food/utensils, insect bites

2. PATHOLOGY (Pathogenesis)

Step-by-step: How HIV destroys the immune system

Step 1 - Entry:

gp120 binds CD4 (primary receptor) on T helper cells
Then binds co-receptor: CCR5 (macrophages, early) or CXCR4 (T cells, late)
gp41 fuses viral envelope with cell membrane

High-yield: Individuals homozygous for CCR5Δ32 deletion are naturally resistant to HIV infection

Step 2 - Replication inside cell:

Reverse transcriptase converts viral RNA → double-stranded DNA
Integrase inserts it into host chromosome as provirus
Viral proteins made → new virions bud off (protease cleaves immature proteins)

Step 3 - Immune destruction:

Direct killing of infected CD4+ cells
Apoptosis of bystander CD4+ cells
CD8+ T cell killing of infected cells
Chronic immune activation → cell exhaustion

Step 4 - Latent reservoir:

Provirus hides in resting memory CD4+ T cells - the main barrier to cure
Cannot be seen or killed by immune system

Why CD4 count matters:

Normal: 500-1500 cells/mm³
As CD4 falls → progressively more severe infections
AIDS defined when CD4 < 200 cells/mm³ OR AIDS-defining illness occurs

3. CLINICAL FEATURES / NATURAL HISTORY

Natural history of HIV - CD4 count and viral load over time

Phase 1: Acute Retroviral Syndrome (2-6 weeks post-infection)

Occurs in 40-90% of newly infected people. Looks like glandular fever (EBV):

Fever (most common)
Lymphadenopathy (axillary, cervical, occipital)
Sore throat (pharyngitis, no exudate)
Maculopapular rash (trunk, 5-10 mm macules, appears 48-72h after fever)
Myalgia/arthralgia
Diarrhea, nausea, weight loss
Retroorbital headache
Painful oral/genital ulcers

Resolves spontaneously in 2-4 weeks. Viral load is VERY high at this point.

Phase 2: Clinical Latency (average 8-10 years without ART)

Patient feels well, may have persistent lymphadenopathy only
Viral replication continues silently in lymphoid tissue
CD4 count gradually drops ~50-100 cells/mm³ per year
Still infectious during this phase

Phase 3: Symptomatic HIV / AIDS

Constitutional symptoms (appear as CD4 falls toward 200):

Fever, night sweats, weight loss (>10% body weight)
Chronic diarrhea
Fatigue, oral candidiasis (thrush), hairy leukoplakia

Opportunistic Infections by CD4 count (High-yield table!)

CD4 Count	Opportunistic Infection
< 500	Oral candidiasis, TB reactivation, Herpes zoster
< 200	PCP (Pneumocystis jirovecii pneumonia) - commonest OI in developed world
< 100	Cerebral toxoplasmosis, Cryptococcal meningitis
< 50	CMV retinitis, MAC (M. avium complex), CNS lymphoma

Key OIs to know:

🔹 PCP (Pneumocystis jirovecii pneumonia)

Subacute dyspnea, dry cough, fever
CXR: bilateral perihilar "ground-glass" interstitial infiltrates
Elevated LDH (marker of severity)
Treat: High-dose Co-trimoxazole (TMP-SMX)
Add corticosteroids if PaO₂ < 70 mmHg (or A-a gradient > 35)

🔹 Cerebral Toxoplasmosis

Headache, fever, focal neuro deficits, seizures
CT/MRI: multiple ring-enhancing lesions (usually bilateral basal ganglia)
Treat: Pyrimethamine + Sulfadiazine + Folinic acid

🔹 Cryptococcal Meningitis

Insidious headache, fever, altered consciousness
CSF: India ink stain = encapsulated yeast; Cryptococcal antigen positive
Treat: Amphotericin B + Flucytosine (induction) → Fluconazole (maintenance)

🔹 CMV Retinitis

Painless visual loss, "floaters"
Fundoscopy: "pizza pie" appearance (hemorrhage + exudates)
Treat: Ganciclovir/Valganciclovir

🔹 MAC (Mycobacterium avium complex)

Disseminated: fever, night sweats, weight loss, anemia, raised ALP
Treat: Azithromycin + Ethambutol

AIDS-defining Malignancies:

🔹 Kaposi Sarcoma (KS) - caused by HHV-8

Violaceous (purple-red) skin nodules, mucous membranes, GI tract, lungs
Spindle cell vascular tumor
In AIDS: widespread and aggressive (vs. sporadic KS in elderly Mediterranean men = localized)
Treat: ART (often causes regression alone) ± liposomal doxorubicin

🔹 B-cell Lymphoma (Burkitt's, primary CNS lymphoma) - EBV driven 🔹 Cervical cancer (women) - HPV driven → AIDS-defining 🔹 Anal carcinoma (men who have sex with men) - HPV driven

CNS manifestations of HIV itself:

HIV encephalopathy / AIDS dementia complex: cognitive decline, memory loss, motor slowing, behavioral change
Peripheral neuropathy: painful sensory neuropathy in hands/feet
Vacuolar myelopathy: progressive leg weakness, spasticity
PML (Progressive Multifocal Leukoencephalopathy): JC virus reactivation → demyelination → focal deficits, no mass effect

4. DIFFERENTIAL DIAGNOSIS

Acute HIV syndrome vs:

Condition	Key Differentiating Feature
EBV Mononucleosis	Tonsillar exudate, splenomegaly, Monospot/heterophile +ve
Secondary Syphilis	Palmoplantar rash, condyloma lata, RPR positive
Rubella	Post-auricular lymphadenopathy, facial rash spreading downward
Toxoplasmosis	Cat exposure, less pharyngitis
Viral Hepatitis	Jaundice prominent, high transaminases
Disseminated Gonorrhea	Migratory arthritis, pustular rash on extremities

Ring-enhancing brain lesion in AIDS:

Toxoplasmosis (multiple, bilateral basal ganglia) - most common
CNS lymphoma (usually single, periventricular; EBV +ve in CSF)
Distinguish: Empirical anti-toxo treatment for 2 weeks → if no improvement → biopsy for lymphoma

5. INVESTIGATIONS

Diagnosing HIV

1st line: 4th Generation Ag/Ab ELISA

Detects both p24 antigen AND HIV-1/2 antibodies
Window period: ~18-45 days from infection
If positive → confirm with differentiation assay

If very recent exposure suspected:

HIV RNA (PCR/Viral Load) - detectable from day 10-15 (shortest window)

Window periods to remember:

RNA/NAT: 10-15 days
p24 antigen: ~18-20 days
Antibody: 3-6 weeks (all seroconvert by 12 weeks)

Monitoring HIV

Test	What it tells you
CD4 count	Degree of immunosuppression; guides prophylaxis
HIV Viral Load (RNA copies/mL)	Treatment efficacy; goal = undetectable (<50 copies/mL) on ART
Genotypic resistance testing	Done at baseline and treatment failure

Baseline workup at HIV diagnosis:

FBC, LFTs, U&E, lipid profile, glucose, urinalysis
Hepatitis B (HBsAg, anti-HBc, anti-HBs) and Hepatitis C serology
Syphilis RPR, TB screening (IGRA or Mantoux)
Toxoplasma IgG, Cryptococcal antigen (if CD4 < 100)
CXR, STI screen, cervical smear (women)
CMV IgG

6. MANAGEMENT

WHEN to start ART

EVERYONE diagnosed with HIV should start ART immediately, regardless of CD4 count

Early treatment = preserves immunity, reduces transmission, reduces non-AIDS complications.

ART Drug Classes (MBBS need-to-know)

Class	Mechanism	Key Drugs
NRTIs (Nucleoside RTIs)	Inhibit reverse transcriptase (chain termination)	Tenofovir (TDF/TAF), Emtricitabine (FTC), Lamivudine (3TC), Zidovudine (AZT)
NNRTIs (Non-nucleoside RTIs)	Non-competitive RT inhibition	Efavirenz, Nevirapine, Rilpivirine
PIs (Protease Inhibitors)	Block viral maturation	Lopinavir, Atazanavir, Darunavir (boosted with ritonavir)
INSTIs (Integrase Inhibitors)	Block DNA integration	Dolutegravir (preferred), Bictegravir, Raltegravir
Fusion inhibitors	Block gp41 fusion	Enfuvirtide
CCR5 antagonists	Block coreceptor	Maraviroc

Standard First-Line Regimen

2 NRTIs + 1 INSTI (or NNRTI)

Most used first-line (single pill, once daily):

Bictegravir/Tenofovir-AF/Emtricitabine (Biktarvy)
Dolutegravir + Tenofovir/Emtricitabine

Opportunistic Infection Prophylaxis

CD4 Threshold	Drug	Purpose
< 200 cells/mm³	Co-trimoxazole (TMP-SMX) daily	PCP prophylaxis
< 100 cells/mm³	TMP-SMX (if Toxo IgG+)	Also covers toxoplasmosis
< 50 cells/mm³	Azithromycin weekly	MAC prophylaxis

Stop prophylaxis once CD4 recovers > threshold on ART for ≥3-6 months.

Post-Exposure Prophylaxis (PEP)

Start within 72 hours (sooner = better; do not start after 72h)
Duration: 28 days
Regimen: Tenofovir-emtricitabine + Dolutegravir

Pre-Exposure Prophylaxis (PrEP)

Tenofovir/emtricitabine daily oral (>99% effective if adherent)
For high-risk uninfected individuals (MSM, sex workers, discordant couples)

IRIS (Immune Reconstitution Inflammatory Syndrome)

Paradoxical worsening of OI symptoms 2-8 weeks after starting ART
Due to recovering immune system attacking pathogens it can now "see"
Manage: NSAIDs; steroids in severe cases; do NOT stop ART

7. LONG-TERM IMPLICATIONS

With effective ART, HIV is now a chronic manageable disease - life expectancy approaches normal. But long-term complications remain:

System	Complication	Notes
Cardiovascular	Accelerated atherosclerosis, ↑MI risk	Chronic inflammation; manage lipids, BP, smoking
Renal	HIV-associated nephropathy (HIVAN)	Collapsing FSGS; mainly in Black patients; ART is treatment
Metabolic	Lipodystrophy, insulin resistance, dyslipidemia	Especially with older PIs; lipoatrophy + central obesity
Neurological	HAND (HIV-associated neurocognitive disorder)	From mild impairment → dementia; CNS reservoir of HIV
Liver	Accelerated fibrosis in HIV/HCV or HIV/HBV co-infection	TDF/TAF also treats HBV
Bone	Osteoporosis, AVN of femoral head	Multifactorial; TDF can reduce bone density
Malignancy	↑ risk of lung, anal, liver, oropharyngeal cancers	Even with good CD4
Psychosocial	Depression, stigma, adherence issues	Major barrier to treatment success

U=U (Undetectable = Untransmittable)

A person on effective ART with an undetectable viral load cannot sexually transmit HIV. This is now proven and is central to prevention messaging.

No Vaccine Yet

Despite decades of research, no licensed HIV vaccine exists (2026)
Broadly neutralizing antibodies and mRNA vaccine platforms under active investigation

QUICK EXAM SUMMARY

Topic	Key Fact
Virus type	Retrovirus (Lentivirus); HIV-1 (global) / HIV-2 (W. Africa)
Cell targeted	CD4+ T helper cells (also macrophages, DCs)
Entry receptor	CD4 + CCR5 or CXCR4
Diagnostic antigen	p24 (in 4th gen ELISA)
AIDS definition	CD4 < 200 OR AIDS-defining illness
Commonest OI in developed world	PCP (treat with TMP-SMX)
Commonest AIDS cancer	Kaposi Sarcoma (caused by HHV-8)
Brain ring-enhancing lesions	Toxoplasmosis (multiple) vs CNS Lymphoma (single)
PEP window	Within 72 hours, 28 days of treatment
First-line ART backbone	2 NRTIs + INSTI (Dolutegravir preferred)
Goal of ART	Undetectable viral load (<50 copies/mL)
IRIS	Worsening of OI 2-8 weeks after starting ART

Sources: Robbins & Kumar Pathologic Basis of Disease (pp. 219-230); Goldman-Cecil Medicine (Chapters 354-357); IAS-USA Panel Guidelines 2024 JAMA 2025; EACS Guidelines v13.0 HIV Med 2026

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