AIDS Pathophysiology

By Dr. Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Editor)

Acquired immune deficiency syndrome (AIDS) is caused by the HIV or human immunodeficiency virus. The infection causes progressive destruction of the cell-mediated immune (CMI) system, primarily by eliminating CD4+ T-helper lymphocytes.

Decreased immunity leads to opportunistic infections and certain cancers. Opportunistic infections are caused by organisms that do not cause infections in healthy individuals. HIV also directly damages certain organs like the brain.

Time taken for AIDS to develop

AIDS indicates advanced HIV disease and has no cure and is considered fatal. The time from HIV infection to death however depends on the management with anti-HIV medications instituted on time and continued over long term.

The time period usually ranges from 6 months (rarely) to 15+ years. In the United Kingdom the average time is around 12 years.

Pathology of AIDS

HIV infection passes through a series of steps or stages before it turns into AIDS. These stages of infection as outlined in 1993 by the Centers for Disease Control and prevention are:

1. Seroconversion illness – this occurs in 1 to 6 weeks after acquiring the infection. The feeling is similar to a bout of flu.
2. Asymptomatic infection – After seroconversion, virus levels are low and replication continues slowly. CD4 and CD8 lymphocyte levels are normal. This stage has no symptoms and may persist for years together.
3. Persistent generalised lymphadenopathy (PGL) – The lymph nodes in these patients are swollen for three months or longer and not due to any other cause.
4. Symptomatic infection – This stage manifests with symptoms. In addition, there may be opportunistic infections. This collection of symptoms and signs is referred to as the AIDS-related complex (ARC) and is regarded as a prodrome or precursor to AIDS.
5. AIDS – this stage is characterized by severe immunodeficiency. There are signs of life-threatening infections and unusual tumours. This stage is characterized by CD4 T-cell count below 200 cells/mm3.
6. There is a small group of patients who develop AIDS very slowly, or never at all. These patients are called nonprogressors.

The pathological spectrum of HIV infection is changing as the infection spreads into new communities with different potential opportunistic diseases, and as medical science devises drugs against HIV replication.

Geographical pathology of HIV/AIDS

Genetics and geographical location has a role in the pattern of opportunistic infections. A second determinant is the speed of decline in the immune system. Many of the opportunistic infections are of low virulence and are only encountered if patients survive with low CMI.

Genetics and earlier site of stay also plays a role. For example, African HIV-infected patients reside in the UK have high rates of tuberculosis and this is usually a reactivation of latent infection acquired in the country of origin.

Some opportunistic infections include;

Viral infections

• Cytomegalovirus (CMV)
• Herpes simplex
• Molluscum contagiosum
• Herpes zoster
• Measles
• Human papilloma virus (HPV)
• Human herpes virus 8 (HV8)
• Epstein-Barr virus (EBV)

Bacterial infections

• Recurrent bacterial pneumonia (commonly Streptococcus pneumoniae)
• Mycobacterium tuberculosis
• Non-tuberculosis mycobacteriosis (particularly M. avium-intracellulare complex)
• Systemic non-typhoid Salmonella infections* (notably S. enteritidis and S. typhimurium)
• Pseudomonas spp. septicaemia and `vasculitis'
• Bartonella spp. (causing bacillary angiomatosis)
• Rhodococcus equi
• Nocardia spp.

Fungal infections

• Candida severe infection
• Pneumocystis jiroveci pneumonia
• Cryptococcus neoformans
• Histoplasma capsulatum
• Coccidioides immitis
• Aspergillus spp.
• Penicillium marneffei
• Protozoal infections
• Toxoplasma gondii
• Cryptosporidium parvum
• Isospora belli
• Leishmania spp.
• Microsporidia spp. (commonly Encephalitozoon intestinalis, Enterocytozoon bieneusi)
• Acanthamoeba spp.
• Trypanosoma cruzi

Tumours

• Kaposi's sarcoma
• Primary cerebral lymphoma
• High-grade non-Hodgkin lymphoma
• Carcinoma (invasive) of the cervix
• Carcinoma of the conjunctiva
• Carcinoma of the anus
• T-cell lymphoma
• Hodgkin's disease
• Lymphoproliferative disease, pre-lymphomatous

Other conditions

• HIV-wasting syndrome (fever, weight loss, diarrhoea)
• HIV-associated dementia or memory loss
• Various dermatitis patterns (e.g. pruritic rash, eosinophilic folliculitis)
• Skeletal myopathy
• Peripheral and autono
• Peripheral and autonomic neuropathy
• Cardiomyopathy
• Pulmonary hypertension
• Vasculitis
• HIV-associated nephropathy (HIVAN)
• Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP)
• Oral and oesophageal ulcers
• Dyshaemopoiesis and marrow serous atrophy

Geographical and ethnic patterns of HIV-associated opportunistic diseases

Geographical and ethnic patterns of HIV-associated opportunistic diseases are also significant. 3

Worldwide infections

• Candidiasis
• Pneumocystosis in infants
• Cryptococcosis
• Progressive multifocal leukoencephalopathy (PML)
• CMV infection in children
• Bacteraemia

Diseases that are geographically restricted

• Leishmaniasis or Kalazar (Mediterranean, Central & South America)
• Penicilliosis (Far East)
• Histoplasmosis (USA, Africa, Caribbean, South America)
• Coccidioidomycosis (USA)
• Trypanosomiasis cruzi (South America)
• Conjunctival carcinoma or cancer (sub-Saharan Africa)

Diseases that vary greatly in prevalence according to socio-economic circumstances, medical facilities and route of HIV infection

• Tuberculosis
• Non-tuberculosis mycobacterioses
• Toxoplasmosis
• Pneumocystosis in adults
• CMV
• Lymphoma
• HIV multinucleate giant cell encephalitis
• Kaposi's sarcoma
• Disease that is ethnically restricted
• HIV-associated nephropathy (in blacks)

Further Reading

• All HIV/AIDS Content
• What is HIV/AIDS?
• HIV-1 versus HIV-2: What’s the Difference?
• What Causes AIDS?
• AIDS Symptoms