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HIV infects cells in the immune system and the central nervous system. The main type of cell that HIV infects is the T helper lymphocyte. These cells play a crucial role in the immune system, by coordinating the actions of other immune system cells. A large reduction in the number of T helper cells seriously weakens the immune system.

HIV infects the T helper cell because it has the protein CD4 on its surface, which HIV uses to attach itself to the cell before gaining entry. This is why the T helper cell is sometimes referred to as a CD4+ lymphocyte. Once it has found its way into a cell, HIV produces new copies of itself, which can then go on to infect other cells.

Over time, HIV infection leads to a severe reduction in the number of T helper cells available to help fight disease. The process usually takes several years.

HIV infection can generally be broken down into four distinct stages: primary infection, clinically asymptomatic stage, symptomatic HIV infection, and progression from HIV to AIDS.

STAGE 1 : Primary HIV Infection

This stage of infection lasts for a few weeks and is often accompanied by a short flu-like illness. In up to about 20% of people the symptoms are serious enough to consult a doctor, but the diagnosis of HIV infection is frequently missed.

During this stage there is a large amount of HIV in the peripheral blood and the immune system begins to respond to the virus by producing HIV antibodies and cytotoxic lymphocytes. This process is known as seroconversion. If an HIV antibody test is done before seroconversion is complete then it may not be positive.

STAGE 2 : Clinically Asymptomatic Stage

This stage lasts for an average of ten years and, as its name suggests, is free from major symptoms, although there may be swollen glands. The level of HIV in the peripheral blood drops to very low levels but people remain infectious and HIV antibodies are detectable in the blood, so antibody tests will show a positive result.

Research has shown that HIV is not dormant during this stage, but is very active in the lymph nodes. A test is available to measure the small amount of HIV that escapes the lymph nodes. This test which measures HIV RNA (HIV genetic material) is referred to as the viral load test, and it has an important role in the treatment of HIV infection.

STAGE 3 : Symptomatic HIV Infection

Over time the immune system becomes severely damaged by HIV. This is thought to happen for three main reasons:

• The lymph nodes and tissues become damaged or 'burnt out' because of the years of activity;
• HIV mutates and becomes more pathogenic, in other words stronger and more varied, leading to more T helper cell destruction;
• The body fails to keep up with replacing the T helper cells that are lost.

As the immune system fails, so symptoms develop. Initially many of the symptoms are mild, but as the immune system deteriorates the symptoms worsen.

Where do opportunistic infections and cancers occur?

Symptomatic HIV infection is mainly caused by the emergence of opportunistic infections and cancers that the immune system would normally prevent. These can occur in almost all the body systems, but common examples are featured in the table below.

As the table below indicates, symptomatic HIV infection is often characterised by multi-system disease. Treatment for the specific infection or cancer is often carried out, but the underlying cause is the action of HIV as it erodes the immune system. Unless HIV itself can be slowed down the symptoms of immune suppression will continue to worsen.

System	Examples of Infection/Cancer
Respiratory system	Pneumocystis jirovecii Pneumonia (PCP) Tuberculosis (TB) Kaposi's Sarcoma (KS)
Gastro-intestinal system	Cryptosporidiosis Candida Cytomegolavirus (CMV) Isosporiasis Kaposi's Sarcoma
Central/peripheral Nervous system	HIV Cytomegolavirus Toxoplasmosis Cryptococcosis Non Hodgkin's lymphoma Varicella Zoster Herpes simplex
Skin	Herpes simplex Kaposi's sarcoma Varicella Zoster

Find out more about opportunistic infections.

STAGE 4 : Progression from HIV to AIDS

As the immune system becomes more and more damaged the illnesses that occur become more and more severe leading eventually to an AIDS diagnosis.

At present in the UK an AIDS diagnosis is confirmed if a person with HIV develops one or more of a specific number of severe opportunistic infections or cancers. In the US, someone may also be diagnosed with AIDS if they have a very low count of T helper cells in their blood. It is possible for someone to be very ill with HIV but not have an AIDS diagnosis.

WHO clinical staging of HIV disease in adults and adolescents (2006 revision)

In resource-poor communities, medical facilities are sometimes poorly equipped, and it is not possible to use CD4 and viral load test results to determine the right time to begin antiretroviral treatment. The World Health Organisation (WHO) has therefore developed a staging system for HIV disease based on clinical symptoms, which may be used to guide medical decision making.

Clinical Stage I:

• Asymptomatic
• Persistent generalized lymphadenopathy

Clinical Stage II:

• Moderate unexplained* weight loss (under 10% of presumed or measured body weight)**
• Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis)
• Herpes zoster
• Angular chelitis
• Recurrent oral ulceration
• Papular pruritic eruptions
• Seborrhoeic dermatitis
• Fungal nail infections

Clinical Stage III:

• Unexplained* severe weight loss (over 10% of presumed or measured body weight)**
• Unexplained* chronic diarrhoea for longer than one month
• Unexplained* persistent fever (intermittent or constant for longer than one month)
• Persistent oral candidiasis
• Oral hairy leukoplakia
• Pulmonary tuberculosis
• Severe bacterial infections (e.g. pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteraemia)
• Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
• Unexplained* anaemia (below 8 g/dl), neutropenia (below 0.5 billion/l) and/or chronic thrombocytopenia (below 50 billion/l)

Clinical Stage IV:***

• HIV wasting syndrome
• Pneumocystis pneumonia
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration or visceral at any site)
• Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
• Extrapulmonary tuberculosis
• Kaposi sarcoma
• Cytomegalovirus infection (retinitis or infection of other organs)
• Central nervous system toxoplasmosis
• HIV encephalopathy
• Extrapulmonary cryptococcosis including meningitis
• Disseminated non-tuberculous mycobacteria infection
• Progressive multifocal leukoencephalopathy
• Chronic cryptosporidiosis
• Chronic isosporiasis
• Disseminated mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
• Recurrent septicaemia (including non-typhoidal Salmonella)
• Lymphoma (cerebral or B cell non-Hodgkin)
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
• Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

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