27th June 2023

Pathophysiology

Human immunodeficiency virus (HIV) is a retrovirus in the Lentivirus genus. The genome of HIV is made of RNA, which is converted into DNA by a reverse transcription enzyme and then integrates this DNA into the host DNA. There are two main types of HIV: HIV 1 and HIV 2. They are morphologically very similar, but HIV-2 is less frequently seen and has lower pathogenicity.

HIV enters cells following attachment to the CD4 receptor and a co-receptor (either CCR5 or CXCR4). HIV chiefly infects CD4+ T-lymphocytes, especially when activated (hence higher risk of transmission if there is an active infection at the site of contact) and establishes quiescent infection in memory CD4+ T cells.

HIV transmission occurs as a result of contact between body fluids and mucosal surfaces or blood, most frequently in the context of penile-vaginal or penile-anal sexual intercourse. Other forms of transmission are vertical transmission (intrauterine, intrapartum or via breast milk) and via contaminated blood products or contaminated sharps.

The progression of HIV follows a set pattern following infection in most patients, however, there is variation between individuals. The first phase in HIV infection is an asymptomatic ‘eclipse’ phase during which the virus spreads through the lymphatic system. It then replicates rapidly with an increase in viral particles and a corresponding immune response. Patients may become symptomatic around this time, but this is usually with mild ‘flu-like’ symptoms. The development of HIV-specific CD8+ T-cells results in a subsequent decrease in viral load. Following this, the disease enters a chronic phase, during which there is a gradual increase in the viral load and a gradual decline in the CD4 count. After a period of years without treatment, a patient gradually develops a CD4 count <200 cells/μL, or alternatively acquires one of a set of diseases characteristic of HIV infection, and they are then said to have entered acquired immunodeficiency syndrome or AIDS. As HIV progresses and the number of CD4+ T lymphocytes declines, the complicating conditions seen are generally less and less prevalent in the population as a whole, and hence more specific to HIV.

Symptoms of HIV infection include:

• Fevers and night sweats
• Myalgia
• Weight loss
• Rash – a range of non-specific rashes, shingles, and scarring
• Lymphadenopathy
• Diarrhoea
• Fungal infection of the nails and chronic vaginal candidiasis
• Changes to neurological function due to HIV encephalopathy or HIV-associated meningitis, toxoplasmosis or cryptococcal disease
• Oral lesions, including mouth ulcers