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Human Immunodeficiency Virus (HIV) Infection

Human Immunodeficiency Virus (HIV) is a viral infection that progressively damages the immune system, mainly by infecting and destroying CD4 T lymphocytes. Without effective treatment, progressive immune deficiency can lead to opportunistic infections, malignancies, and Acquired Immunodeficiency Syndrome (AIDS)

Also called

HIV Disease

ICD-10

B20

Specialty

Infectious

Onset

Chronic

Reviewed

August 2026
On This Page

Overview

-Human Immunodeficiency Virus (HIV) transmitted mainly through:

  • Sexual contact
  • Blood exposure
  • Sharing contaminated needles
  • Mother-to-child transmission during pregnancy, delivery, or breastfeeding

 

-The infection progresses through an acute phase, a chronic phase, and, without adequate treatment, advanced immune deficiency.

Modern antiretroviral therapy (ART) can suppress viral replication, preserve immune function, prevent progression, and greatly reduce transmission.

Etiology & Risk Factors

-Etiology

–The causative virus is Human Immunodeficiency Virus (HIV), mainly:

  • HIV-1 — responsible for most infections worldwide
  • HIV-2 — less common and concentrated mainly in West Africa

The virus primarily targets CD4 T lymphocytes, macrophages, and dendritic cells.

 

-Risk Factors for Human Immunodeficiency Virus (HIV)

  • Unprotected sexual exposure
  • Multiple sexual partners
  • Sharing injection equipment
  • Exposure to contaminated blood
  • Perinatal exposure
  • High-risk occupational exposure

Pathophysiology

Human Immunodeficiency Virus (HIV) enters the body → binds CD4 cells → viral replication → progressive CD4 T-cell loss and dysfunction → impaired cellular immunity → increased susceptibility to opportunistic infections and malignancies → advanced immune deficiency/AIDS

Clinical Presentation

-Symptoms:

Acute Human Immunodeficiency Virus (HIV) Infection

Often occurs 2–4 weeks after infection and may resemble a viral illness:

  • Fever
  • Sore throat
  • Rash
  • Lymphadenopathy
  • Myalgia
  • Headache
  • Fatigue
  • Oral ulcers

Chronic Human Immunodeficiency Virus (HIV)  Infection

May remain asymptomatic for years.

Possible symptoms include:

  • Persistent lymphadenopathy
  • Recurrent infections
  • Weight loss
  • Chronic diarrhea
  • Fever

-Signs:

  • Generalized lymphadenopathy
  • Weight loss
  • Oral candidiasis
  • Recurrent infections
  • Skin manifestations
Human Immunodeficiency Virus (HIV) Overview
Human Immunodeficiency Virus (HIV) Overview

History Taking

-Ask about:

  • Recent sexual exposure
  • Condom use
  • Number and type of sexual partners
  • Previous sexually transmitted infections
  • Injection drug use
  • Needle sharing
  • Previous blood transfusions when relevant
  • Occupational exposure
  • Pregnancy or breastfeeding status when applicable
  • Previous HIV testing
  • Previous opportunistic infections
  • Weight loss
  • Chronic diarrhea
  • Fever and night sweats

Physical Examination

-General Examination

  • Weight and nutritional status
  • Temperature
  • Lymph nodes
  • Skin and mucous membranes

 

Look for:

  • Lymphadenopathy
  • Oral candidiasis
  • Skin lesions
  • Wasting
  • Signs of opportunistic infection

-System-Specific Examination:

  • Respiratory system
  • Neurological system
  • Oral cavity
  • Skin
  • Abdomen

Investigations

-Complete Blood Count

May show:

  • Anemia

  • Leukopenia

  • Thrombocytopenia

It is mainly used to assess complications and overall health rather than establish the diagnosis.

-Biochemistry / Specific Tests

 

Human Immunodeficiency Virus (HIV) Testing

Initial laboratory testing commonly uses a combination antigen/antibody test.

A reactive screening test requires an appropriate confirmatory testing algorithm.

 

Human Immunodeficiency Virus (HIV)-1 RNA

Used when:

  • Acute infection is suspected

  • Initial testing is indeterminate

  • Viral load needs to be measured

CD4 T-Cell Count

Used to assess:

  • Degree of immune suppression

  • Risk of opportunistic infections

  • Need for certain prophylactic therapies

  • Baseline immune status

Viral Load

Measures plasma Human Immunodeficiency Virus (HIV) RNA and is the main laboratory marker used to monitor response to ART.

Baseline Assessment

Common baseline tests include:

  • Renal function

  • Liver function

  • Glucose

  • Lipid profile

  • Hepatitis A, B, and C testing

Diagnosis

-Diagnosis of Human Immunodeficiency Virus (HIV) is established by:

Screening HIV antigen/antibody test → laboratory confirmation → Human Immunodeficiency Virus (HIV) -1 RNA when acute infection or an indeterminate result is suspected

After diagnosis:

CD4 count + viral load → assess immune status and establish baseline for treatment monitoring

AIDS is the most advanced stage and is defined by CD4 count <200 cells/mm³ or an AIDS-defining condition

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Management

HIV · Management — When to Start & Monitoring

When to Start ART
Universal rule
Treat ALL HIV+ patients regardless of CD4 count — WHO 2015 / DHHS guideline
Start as soon as possible after diagnosis — ideally same day (rapid ART)
Earlier treatment = ↓ transmission, ↓ AIDS-defining illness, ↓ non-AIDS morbidity
Urgent / prioritise
CD4 <200 — high AIDS risk; start immediately
AIDS-defining illness — start within 2 weeks (except TB meningitis — delay 4–8 wks)
Pregnancy — start immediately regardless of CD4
HIV nephropathy, HBV co-infection — urgent
Before starting — workup
HIV viral load + CD4 count
Resistance testing (genotype) — especially if transmitted resistance suspected
HLA-B*5701 — before abacavir (hypersensitivity)
Hepatitis B/C, TB screen, STI screen, LFTs, renal function
Monitoring on ART
ParameterTarget / GoalFrequencyAction if abnormal
HIV Viral LoadUndetectable <50 copies/mL — treatment successAt baseline, 4 wks, 3 months, then every 3–6 monthsIf detectable at 6 months → resistance testing → switch regimen
CD4 CountShould rise ~100–150 cells/μL/year on effective ARTEvery 3–6 months until >200, then annuallyCD4 <200 → add OI prophylaxis
Renal function (eGFR)Monitor for TDF toxicity (proximal tubulopathy)Every 3–6 monthseGFR drop → switch TDF to TAF or ABC
Lipids / glucoseMetabolic syndrome risk — especially with PIsAnnuallySwitch PI; statin therapy
LFTsHepatotoxicity (NVP, PIs) + HBV flare if HBV+Every 3–6 monthsSwitch agent; manage HBV
Goal of ART: Viral load <50 copies/mL (undetectable) = U=U (Undetectable = Untransmittable). CD4 recovery reduces OI risk. Lifelong therapy — never stop.

HIV · Antiretroviral Drug Classes

ARV Drug Classes — Mechanism & Key Agents
NRTIs
NRTIs
Nucleoside Reverse Transcriptase Inhibitors
Mechanism: Chain terminator — block reverse transcriptase (DNA synthesis)
  • Tenofovir (TDF / TAF) — backbone of most regimens; TAF safer for kidneys/bones
  • Emtricitabine (FTC) — paired with TDF/TAF
  • Abacavir (ABC) — requires HLA-B*5701 testing; hypersensitivity risk
  • Lamivudine (3TC) — also active against HBV
  • Zidovudine (AZT) — PMTCT; anaemia side effect
SE: mitochondrial toxicity, lipoatrophy, renal (TDF)
NNRTIs
NNRTIs
Non-Nucleoside Reverse Transcriptase Inhibitors
Mechanism: Bind allosteric site of RT — not chain terminator
  • Efavirenz (EFV) — once daily; CNS side effects (vivid dreams, depression)
  • Rilpivirine (RPV) — fewer SE; requires food; not if VL >100,000
  • Doravirine (DOR) — newer; fewer drug interactions
  • Nevirapine (NVP) — hepatotoxicity risk; avoid if CD4 >250 (F) / 400 (M)
SE: CNS (EFV), rash, hepatotoxicity (NVP), CYP450 interactions
PIs
PIs
Protease Inhibitors
Mechanism: Block HIV protease → immature non-infectious virions
  • Darunavir (DRV) — boosted with ritonavir or cobicistat; high barrier to resistance
  • Atazanavir (ATV) — once daily; jaundice (benign ↑ bilirubin)
  • Lopinavir/r (LPV/r) — used in resource-limited settings; GI SE
  • Ritonavir (RTV) — pharmacokinetic booster only (inhibits CYP3A4)
SE: GI, dyslipidaemia, lipodystrophy, hyperglycaemia, drug interactions
INSTIs
INSTIs
Integrase Strand Transfer Inhibitors
Mechanism: Block integration of HIV DNA into host genome
  • Dolutegravir (DTG) — preferred 1st line; high barrier to resistance; once daily
  • Bictegravir (BIC) — in Biktarvy (BIC/TAF/FTC); excellent tolerability
  • Cabotegravir (CAB) — injectable long-acting; monthly/bimonthly
  • Raltegravir (RAL) — older; twice daily; fewer drug interactions
SE: weight gain (DTG), insomnia, creatinine rise (falsely — not true GFR drop)
Entry inhibitors
Entry
CCR5 Antagonists & Fusion Inhibitors
CCR5 antagonist:
  • Maraviroc (MVC) — blocks CCR5 co-receptor; requires tropism testing first (R5-tropic only)
Fusion inhibitor:
  • Enfuvirtide (T-20) — SC injection; salvage therapy only; expensive
Attachment inhibitor:
  • Fostemsavir — gp120 attachment; for heavily treatment-experienced
Used mainly in salvage / MDR-HIV
Capsid inhibitor
New
Capsid Inhibitor & Long-Acting Injectable
Lenacapavir (LEN):
  • First-in-class capsid inhibitor — multiple steps of HIV lifecycle
  • SC injection every 6 months — highest barrier to resistance
  • Approved for heavily treatment-experienced MDR-HIV
Long-acting injectable ART:
  • Cabotegravir + rilpivirine (CAB+RPV) IM — monthly or every 2 months
  • Alternative to daily pills for adherence challenges
Newest class — changing landscape of HIV treatment

Complications

HIV Complications · Opportunistic Infections by CD4 Count

Any CD4
All stages
TB (most common OI worldwide)
Bacterial pneumonia (recurrent)
Herpes zoster (shingles)
Oral candidiasis (thrush)
Kaposi sarcoma (HHV-8)
<200
AIDS-defining
PCP — Pneumocystis pneumonia
Oesophageal candidiasis
Cryptosporidiosis
Microsporidiosis
Miliary TB
<100
Severe
Toxoplasmosis (brain)
Cryptococcal meningitis
CMV retinitis / colitis
Bartonellosis
Progressive multifocal leukoencephalopathy (PML)
<50
Profound
MAC — Mycobacterium avium complex
CMV disseminated
Disseminated histoplasmosis
Disseminated coccidioidomycosis
CNS lymphoma
Pulmonary Complications
PCP — CD4 <200
  • Dry cough, progressive dyspnea, fever — insidious onset
  • CXR: bilateral perihilar ground-glass — may be normal early
  • LDH markedly elevated; exercise desaturation
  • Dx: BAL + silver stain / immunofluorescence
  • Tx: Co-trimoxazole (high dose) + steroids if PaO₂ <70
TB — Any CD4
  • Most common OI worldwide — atypical CXR in low CD4
  • CD4 <200: miliary, extrapulmonary, lower lobe — no cavitation
  • CD4 >200: classic upper lobe cavitation
  • Start ART 2 weeks after TB therapy (except TB meningitis — 4–8 wks)
  • IRIS common — do NOT stop ART
Other pulmonary
  • Bacterial pneumonia — recurrent (>2×/yr) = AIDS-defining; S. pneumoniae most common
  • CMV pneumonitis — CD4 <50; bilateral interstitial; treat: ganciclovir
  • Kaposi sarcoma (pulmonary) — haemoptysis, nodules, pleural effusion
  • Lymphoma — B-cell NHL; mediastinal involvement

HIV Complications · CNS, GI & Systemic

CNS Complications
Toxoplasma encephalitis — CD4 <100
  • Fever, headache, focal deficits, seizures
  • CT/MRI: multiple ring-enhancing lesions — basal ganglia
  • Toxoplasma IgG positive (90%)
  • Tx: Pyrimethamine + sulfadiazine + folinic acid × 6 wks
  • DDx: CNS lymphoma (single lesion, EBV+, PET avid)
Cryptococcal meningitis — CD4 <100
  • Subacute headache, fever, neck stiffness — may be subtle
  • LP: high opening pressure, India ink + (80%), CrAg positive
  • Tx: Amphotericin B + flucytosine × 2 wks → fluconazole
  • LP drainage critical — raised ICP = major cause of death
  • Maintenance: Fluconazole lifelong until CD4 >200
PML & HIV encephalopathy
  • PML (JC virus) — CD4 <100; focal deficits, no fever; white matter lesions; no enhancement; no treatment except ART
  • HIV encephalopathy (HAND) — subcortical dementia; cognitive decline, motor slowing; treated with ART
  • CNS lymphoma — single enhancing lesion; EBV in CSF; treat with whole-brain RT
GI & Systemic Complications
GI infections
  • Oesophageal candidiasis — CD4 <200; dysphagia + odynophagia; Tx: fluconazole
  • CMV colitis — CD4 <50; bloody diarrhoea, ulcers; Tx: ganciclovir
  • Cryptosporidiosis — CD4 <200; profuse watery diarrhoea; no reliable treatment — ART is key
  • MAC — CD4 <50; chronic diarrhoea, fever, weight loss, high LDH; Tx: azithromycin + ethambutol
CMV retinitis — CD4 <50
  • Floaters, visual field loss, painless — "pizza pie" appearance on fundoscopy
  • Fluffy white perivascular exudates + haemorrhage
  • Tx: Ganciclovir / valganciclovir — lifelong until CD4 >100 × 3–6 months
  • Most common cause of blindness in AIDS patients
Malignancies
  • Kaposi sarcoma — HHV-8; violaceous skin/mucosal lesions; any CD4; Tx: ART ± chemotherapy
  • NHL (non-Hodgkin lymphoma) — EBV-related; aggressive B-cell; Tx: R-CHOP
  • Cervical cancer — HPV-related; AIDS-defining; annual cervical screening
  • Anal cancer — HPV; MSM; high-resolution anoscopy
IRIS: Paradoxical worsening after ART initiation — recovering immune system attacks existing OIs. Common with TB, Cryptococcus, CMV. Treat with steroids if severe — never stop ART.

Prognosis

With effective ART, people living with Human Immunodeficiency Virus (HIV) can achieve long-term viral suppression and substantially improved health outcomes. WHO notes that effective ART reduces HIV-associated illness and death and prevents onward sexual transmission.

Key Points / Clinical Pearls

  • Human Immunodeficiency Virus (HIV) is a virus that primarily targets CD4 T lymphocytes.
  • HIV-1 causes most infections worldwide.
  • Transmission occurs mainly through sexual exposure, blood exposure, and mother-to-child transmission.
  • Acute infection may present with a flu-like illness, rash, sore throat, and lymphadenopathy.
  • Chronic infection may remain asymptomatic for years.
  • Progressive CD4 loss causes immune deficiency.
  • Fourth-generation antigen/antibody testing is commonly used for initial diagnosis.
  • Human Immunodeficiency Virus (HIV) -1 RNA is important when acute infection is suspected.
  • CD4 count assesses immune status and opportunistic infection risk.
  • Viral load is the main marker of treatment response.
  • AIDS is defined by CD4 <200 cells/mm³ or an AIDS-defining condition.
  • ART should be started as soon as possible after diagnosis.