HIV and AIDS
Background
Human immunodeficiency virus (HIV) is a lentivirus from the subfamily of retroviruses. Lentiviruses typically have long latent phases following infection and symptom onset.HIV causes immunodeficiency via infecting and destroying immune cells, in particular CD4 cells, a class of T-lymphocyte.
Epidemiology and transmission
HIV is transmitted through exposure to infected bodily fluids. Key routes include:- Direct inoculation via contaminated needles, instruments, or blood products
- Mucocutaneous exposure through open wounds or mucous membranes
- Sexual transmission through semen, preseminal fluid, rectal and vaginal secretions, during vaginal, anal, or oral sex
- Vertical transmission from mother to child during pregnancy, childbirth, or breastfeeding
- Human bites that break the skin (rare)
In high-income countries, major risk groups include:
- Men who have sex with men (MSM)
- Intravenous drug users
- Individuals or partners from high-prevalence regions
In low- and middle-income countries, transmission is predominantly:
- Heterosexual
- Vertical (especially during labour)
- Via unscreened transfusions or unsafe medical procedures
Risk factors for HIV
- Current or former partner who is infected with HIV.
- From an area with high HIV prevalence.
- Men who have sex with men (MSM).
- Female sexual contacts of MSM.
- Transwomen.
- Multiple sexual partners, engage in high-risk sexual practices such as ‘chemsex’, or have a history of other sexually transmitted infection (such as syphilis, chlamydia, and gonorrhoea).
- History of injecting drug use.
- Current or previous sex workers.
- Have been raped.
- History of blood transfusions, transplants, or other risk-prone procedures in countries without rigorous procedures for HIV screening.
- Occupational exposure eg needle-stick
Note: Antiretroviral therapy (ART) during pregnancy and elective caesarean section significantly reduce vertical transmission risk.
Pathogenesis
HIV primarily targets CD4+ T helper cells leading to:- Gradual depletion of CD4+ cells
- Impaired cell-mediated immunity
- Dysfunctional B-cell responses due to inadequate T-cell help
- Increased susceptibility to opportunistic infections and malignancies
The HIV virus infects cells via CD4 receptors, primarily T-cells, as T-cells are infected and become depleted immunity wanes. Low CD4 counts and high viral loads are a poor prognostic sign.
Clinical Features
- Incubation: 2–6 weeks post-exposure (HIV tests may be negative during this window)
- Seroconversion illness: A glandular fever-like or flu-like illness typically lasting around 1-2 weeks including fever, lymphadenopathy, pharyngitis, myalgia, headache and maculopapular rash
- Latent (chronic) phase: Variable duration that may last months to years. Viral replication typically continues at low levels. Some patients who progress to advanced HIV disease (AIDS) within 1–2 years are termed rapid progressors whilst others may maintain effective immune function more than 10 years later (these patients are termed slow progressors).
- Disease progression to AIDS is defined by CD4+ count <200 cells/µL or presence of AIDS-defining illness
Following infection a latent asymptomatic period typically lasts 8-16 years. Treatment is based on reducing viral replication and maintaining a low viral load.
Common opportunistic infections and malignancies:
- Bacterial: Mycobacterium tuberculosis, Listeria, Streptococcus pneumoniae, Salmonella spp.
- Viral: HSV, CMV, VZV, measles
- Fungal: Cryptococcus neoformans, Pneumocystis jirovecii, Candida spp.
- Protozoal: Toxoplasma gondii
- Malignancy: Kaposi sarcoma, Non-Hodgkin lymphoma
Diagnosis
- Initial diagnosis: Combined HIV antibody and p24 antigen test
- Confirmatory testing: A second blood sample is required
- Plasma HIV RNA (viral load)
- CD4+ T cell count
| Test Type | Description | Window Period | Use Case |
|---|---|---|---|
| Fourth-generation antigen/antibody tests | Detect both HIV-1/2 antibodies and p24 antigen. These are the standard tests used in the UK. | 2–4 weeks post-exposure | Routine screening and diagnostic testing. |
| Third-generation antibody-only tests | Detect antibodies to HIV-1/2. Less commonly used due to longer window period. | 3–12 weeks post-exposure | Used when fourth-generation tests are unavailable. |
| HIV RNA PCR (viral load) | Detects viral RNA. Used for early detection and monitoring. | 1–2 weeks post-exposure | Confirmatory testing and monitoring treatment response. |
| Point-of-care (rapid) tests | Provide results within minutes. May be antibody-only or antigen/antibody tests. | Varies; generally longer window period | Settings where immediate results are beneficial. |
| Self-sampling and self-testing kits | Allow individuals to collect samples at home. | Varies depending on the test used | Increasing access to testing in non-clinical settings. |
Note: During the early seroconversion period, antibody tests may be negative. Repeat testing is recommended after 3 months if exposure is suspected.
Treatment
Following diagnosis of HIV the mainstay of treatment is anti-retroviral therapy (ART). Goals of ART are:- Suppress viral replication to undetectable levels
- Prevent immune deterioration and opportunistic infections
- Improve quality of life and life expectancy
- Minimise drug-related toxicity
Key principles:
- Early initiation recommended before irreversible immune damage
- Regimens must be tailored for adherence and tolerability
- Strict adherence is essential to avoid resistance
- Combination therapy reduces the risk of viral escape and resistance
Drug classes:
- Nucleoside/tide reverse transcriptase inhibitors (NRTIs)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Protease inhibitors (PIs)
- Integrase inhibitors (IIs)
- Entry inhibitors (EIs)
Adverse effects of ART:
- Hypersensitivity reactions
- Psychiatric effects: nightmares, mood changes
- Metabolic: hyperlipidaemia, type 2 diabetes
- Lipodystrophy, lipoatrophy
- Renal: Fanconi syndrome, nephrolithiasis
- Hepatic: lactic acidosis, hepatic toxicity
- Neurological: peripheral neuropathy
- Haematological: bone marrow suppression
- Gastrointestinal: pancreatitis
AIDS definition
Acquired immunodeficiency syndrome (AIDS) is increasingly being referred to as advanced HIV disease.
AIDS is defined by:
Acquired immunodeficiency syndrome (AIDS) is increasingly being referred to as advanced HIV disease.
AIDS is defined by:
- CD4 count less than 200 cells per microlitre OR
- The presence of an AIDS defining illness (see box below)
AIDS defining illnesses
| Category | Illnesses |
|---|---|
| Neoplasms | Cervical cancer Non-Hodgkin lymphoma Kaposi’s sarcoma |
| Bacterial infections | Mycobacterium tuberculosis, pulmonary or extrapulmonary Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumonia, recurrent (two or more episodes in 12 months) Salmonella septicaemia, recurrent |
| Viral infections | Cytomegalovirus retinitis Cytomegalovirus, other (except liver, spleen, glands) Herpes simplex, ulcer(s) more than 1 month/bronchitis/pneumonitis Progressive multifocal leukoencephalopathy |
| Parasitic infections | Cerebral toxoplasmosis Cryptosporidiosis diarrhoea, more than 1 month. Isosporiasis, more than 1 month. Atypical disseminated leishmaniasis Reactivation of American trypanosomiasis (meningoencephalitis or myocarditis) |
| Fungal infections | Pneumocystis pneumonia (PCP) Candidiasis, oesophageal Candidiasis, bronchial/tracheal/pulmonary Cryptococcosis, extrapulmonary Histoplasmosis, disseminated/extrapulmonary Coccidioidomycosis, disseminated/extrapulmonary Penicilliosis, disseminated |