Stages of HIV Infection

back to top Introduction

HIV infects cells in the immune system and the central nervous system. One of the main type of cells 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 number of T helper cells is measured by having a CD4 test and is referred to as the CD4 count. It can take several years before the CD4 count declines to the point that an individual needs to begin antiretroviral treatment. Without treatment, the CD4 count continues to decline to very low levels, at which point the individual is said to have progressed to AIDS.

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.

back to top 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 HIV 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.

back to top 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.

back to top 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.

Antiretroviral treatment is usually started once an individuals CD4 count (the number of T helper cells) drops to a low level, an indication that the immune system is deteriorating. Treatment can stop HIV from damaging the immune system, therefore, HIV-infected individuals on treatment usually remain clinically asymptomatic.

However, in HIV-infected individuals not receiving treatment or on treatment that is not working, the immune system fails and symptoms develop. Initially many of the symptoms are mild, but as the immune system deteriorates the symptoms worsen.

Symptomatic HIV infection is mainly caused by the emergence of certain opportunistic infections that the immune system would normally prevent. This stage of HIV infection is often characterised by multi-system disease and infections can occur in almost all body systems.

Treatment for the specific infection 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.

back to top STAGE 4 : Progression from HIV to AIDS

As the immune system becomes more and more damaged the individual may develop increasingly severe opportunistic infections and cancers, leading eventually to an AIDS diagnosis.

A clinical criteria is used by WHO to diagnose the progression to AIDS, this differs slightly between adults and children under five. In adults and children (aged 5 or over) the progression to AIDS is diagnosed when any condition listed in clinical stage 4 is diagnosed and/or the CD4 count is less than 200 cells/mm³ or a CD4 percentage less than 15. In children younger than five, an AIDS diagnosis is based on having any stage 4 condition and/or a CD4 percentage less than 20 (children aged 12-35 months) and a CD4 percentage less than 25 (children less than 12 months). The criteria for diagnosing AIDS may differ depending on individual country guidelines.

back to top Examples of opportunistic infections and cancers

The table below shows examples of common opportunistic infections and cancers and the body systems that they occur in.

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	Cytomegolavirus Toxoplasmosis Cryptococcosis Non Hodgkin's lymphoma Varicella Zoster Herpes simplex
Skin	Herpes simplex Kaposi's sarcoma Varicella Zoster

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

In resource-poor settings, medical facilities are sometimes poorly equipped and tests to measure CD4 count and viral load are unavailable. In this case, another method to determine whether an individual should begin treatment is used. The World Health Organisation (WHO) 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

Source back to top

• Interim WHO clinical staging of HIV/AIDS and HIV/AIDS case definitions for surveillance - 2005

Notes

• * Unexplained refers to where the condition is not explained by other conditions.
• ** Assessment of body weight among pregnant woman needs to consider the expected weight gain of pregnancy.
• *** Some additional specific conditions can also be included in regional classifications (such as the reactivation of American trypanosomiasis [meningoencephalitis and/or myocarditis] in the WHO Region of the Americas and penicilliosis in Asia).