HIV

Chronic, progressive infection characterized by destruction and dysfunction of CD4⁺ T lymphocytes, leading to acquired immunodeficiency and increased susceptibility to opportunistic infections, malignancies, and systemic complications.

Aetiology

Causative Agents

  • HIV-1 (most common worldwide, higher virulence)
  • HIV-2 (less transmissible, slower disease progression)

Viral Structure and Replication

  • Enveloped RNA virus from the Retroviridae family
  • Uses CD4 receptor and co-receptors CCR5 or CXCR4 to enter host cells
  • Reverse transcription of viral RNA into DNA
  • Integration of viral DNA into host genome
  • Lifelong infection due to viral persistence

Modes of Transmission

  • Sexual contact (heterosexual and homosexual)
  • Blood and blood products (transfusion, needle sharing)
  • Vertical transmission (mother-to-child during pregnancy, delivery, or breastfeeding)
  • Occupational exposure (needle-stick injuries)

Clinical presentation

WHO Clinical Staging of HIV Infection

Stage 1: Asymptomatic HIV Infection

Clinical Features:
  • Asymptomatic
  • Persistent generalized lymphadenopathy may be present
Functional Status:
  • Normal daily activity

Stage 2: Mild HIV Disease

Clinical Features:
  • Unexplained moderate weight loss (<10% of body weight)
  • Recurrent upper respiratory tract infections
  • Herpes zoster
  • Angular cheilitis — stomatitis
  • Seborrheic dermatitis
  • Recurrent oral ulcerations
  • Papular pruritic eruptions
  • Onycomycosis

Stage 3: Advanced HIV Disease

Clinical Features:
  • Unexplained severe weight loss (>10% of body weight)
  • Chronic diarrhea (>1 month)
  • Persistent fever (>1 month)
  • Oral candidiasis
  • Oral hairy leukoplakia
  • Pulmonary tuberculosis
  • Severe bacterial infections (e.g., pneumonia, empyema)
  • Acute necrotizing ulcerative gingivitis or periodontitis
  • Unexplained anemia, neutropenia, or thrombocytopenia

Stage 4: Severe HIV Disease (AIDS)

Clinical Features (AIDS-defining illnesses):
  • HIV wasting syndrome
  • Pneumocystis jirovecii pneumonia
  • Chronic herpes simplex infection (>1 month or visceral)
  • Esophageal candidiasis
  • Extrapulmonary tuberculosis
  • Kaposi sarcoma
  • Non-Hodgkin lymphoma
  • Toxoplasmosis of the brain
  • Cryptococcal meningitis
  • Cytomegalovirus disease
  • Progressive multifocal leukoencephalopathy

Investigations

Investigation
Purpose
HIV Ag/Ab test
Diagnosis
HIV RNA
Viral activity & treatment response
CD4 count
Immune status & staging
Resistance testing
ART selection
Infection screening
Detect OIs and co-infections
Routine labs
Baseline & toxicity monitoring

Management

First-Line ART Regimens

Standard first-line regimen consists of combination therapy:
Preferred regimen:
  • Two NRTIs + one INSTI
  • Two NRTIs + one NNRTI
NRTIs (Nucleoside Reverse Transcriptase Inhibitor)
  • AZT = Zidovudine (100mg)
  • 3TC = Lamivudine (150mg)
  • TDF = Tenofovir (300mg)
  • FTC = Emtricitabine
NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitor)
  • EFV = Efavirenz (200mg & 600mg)
  • NVP = Nevirapine (200mg)
Regimen
Drug Components
Drug Classes
Clinical Notes
TDF + 3TC + DTG
Tenofovir disoproxil fumarate + Lamivudine + Dolutegravir
2 NRTIs + INSTI
Preferred first-line regimen; high potency, high barrier to resistance
TAF + FTC + DTG
Tenofovir alafenamide + Emtricitabine + Dolutegravir
2 NRTIs + INSTI
Better renal and bone safety
ABC + 3TC + DTG
Abacavir + Lamivudine + Dolutegravir
2 NRTIs + INSTI
Use only if HLA-B*5701 negative
TDF + 3TC + EFV
Tenofovir + Lamivudine + Efavirenz
2 NRTIs + NNRTI
Alternative when INSTI not available
AZT + 3TC + EFV
Zidovudine + Lamivudine + Efavirenz
2 NRTIs + NNRTI
Used if tenofovir contraindicated

Side Effects of ART Drugs (by Class)

Nucleoside / Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Drug
Major Adverse Effects
Key Clinical Notes
Zidovudine (AZT)
Anemia, neutropenia, myopathy
Bone marrow suppression
Tenofovir (TDF)
Nephrotoxicity, Fanconi syndrome, ↓ bone mineral density
Monitor creatinine & phosphate
Lamivudine (3TC)
Rare: pancreatitis
Generally well tolerated
Emtricitabine (FTC)
Hyperpigmentation (palms/soles)
Benign cosmetic effect
Abacavir (ABC)
Hypersensitivity reaction (HLA-B*5701), MI risk
Screen HLA-B*5701 before use
Didanosine (ddI)
Pancreatitis, peripheral neuropathy
Largely obsolete
Stavudine (d4T)
Lipoatrophy, neuropathy, lactic acidosis
Obsolete due to toxicity
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Drug
Major Adverse Effects
Key Clinical Notes
Efavirenz (EFV)
CNS effects (vivid dreams, psychosis), rash
Avoid in severe psychiatric illness
Nevirapine (NVP)
Hepatotoxicity, severe rash (SJS/TEN)
High risk in women with CD4 >250
Etravirine
Rash
Less CNS toxicity
Rilpivirine
Depression, QT prolongation
Avoid if high viral load