Infection with HIV causes a spectrum of clinical problems, beginning at the time of sero-conversion (infection) and terminating with AIDS and death. It is now recognised that it may take between 7 and 10 years, and possibly longer, for AIDS to develop after sero-conversion.
The clinical stages of HIV infection are:
- Acute infection
- Asymptomatic disease/silent phase
- Early symptomatic disease
Stage 1: Acute Infection
Acute infection can occur by exposure to the bodily fluids of an infected person. Importantly, this is why any action that increases exposure to bodily fluids will increase the risk of infection.
Specific behaviours include:
- Sexual Transmission
- Largely heterosexual in developing countries.
- Male homosexuals account for a significant proportion in developed countries
- Parenteral Transmission
- Needle-sharing amongst drug users (mostly in developed countries)
- Re-using inadequately sterilized needles
- Transfusion of HIV infected blood or blood products
- Needlestick injury (affects medical professionals mostly)
- Vertical Transmission (from mother to foetus or baby during the period immediately before and after birth - across the placenta, in the breast milk, or through direct contact during or after birth.)
Stage 2: Asymptomatic Disease / Primary HIV Infection
Following infection there is a period of intense, unchecked viral replication that occurs about two to four weeks after infection and lasts about one to two weeks, after which the patient recovers and is henceforth seropositive for HIV antibodies.
Though HIV replication is massive, most patients only experience moderate flu-like symptoms at this stage. Typically, the illness is sudden in onset and is characterized by a fever, swelling of the lymph glands, a measles like rash over the whole body and ulcers in the mouth and sometimes on the genitalia.
Disease of the gastrointestinal tract is often involved, manifesting as anorexia, nausea, vomiting and diarrhoea. Patients may also present with inflammation of the pharynx and dysphasia, meningitis or encephalitis.
This acute HIV syndrome does not occur in all individuals infected with the virus - and many individuals who are HIV positive, do not recall ever having experienced the illness. It has been estimated that approximately 50–70% of individuals who are HIV+ experience acute HIV illness. This syndrome is rarely seen in children.
Stage 3: Early Symptomatic Disease
The immune system is now engaged in a constant battle with the rapidly replicating virus. Approximately 50 million to 2 billion new virus particles are created each day. The immune system responds by replenishing the peripheral blood with up to 2 billion new CD4+ cells per day.
The immune system can hold HIV in check for many years, but will eventually begin to lose the battle. The virus begins to destroy the CD4+ cell population. As CD4+ counts continue to drop, signs and symptoms more specific to HIV disease arise.
These signs and symptoms are:
- Persistent generalised lymphodenopathy (PGL)
- Oral lesions (thrush, leukoplakia, ulcers)
- Shingles (painful rash affecting a defined area of skin)
- Thrombocytopenia (reduced platelet count)
- Early stages of neurological disease (aseptic meningitis/peripheral neuropathy)
Stage 4: Acquired Immuno-Deficiency Syndrome
Over the years, the diagnostic elements of this end-stage of HIV infection have undergone various changes under different classification systems. The advent of AIDS marks an important milestone in the course of the infection. An irreversible step has been reached when the diagnosis of AIDS is made. Recovery from individual opportunistic infections may well occur and there may also be remission for tumours. However, they do recur, usually with increasing severity and frequency and become more and more difficult to treat until finally the patient dies, on an average after about 18 months to two years after the onset of AIDS.
Essentially, the components of AIDS consist of the direct consequences of damage by HIV as well, as the indirect consequences of immunosuppression.
The patient has developed AIDS if the following are present:
- The patient is HIV positive
- The CD4+ count is 200 cells per mm3 or less
- There is an AIDS defining disease such as:
- Kaposi’s sarcoma
- Pneumocystis carinii pneumonia
- Retinitis due to cytomegalovirus
- Meningitis/encephalitis due to cryptococcal or toxoplasmosis infection
- Pulmonary, miliary or extra-pulmonary tuberculosis
- Dementia for no other reason (HIV encephalopathy)
- Other cancers such as lymphoma also associated with AIDS. These may present with enlargement of lymph nodes, liver and/or spleen.
Approximately 80% of patients with AIDS die of secondary infections caused by bacteria, protozoa, fungi or other viruses. Many of these microbes can appear in HIV-infected patients before the onset of AIDS. Many of these secondary infections can be treated at any stage of HIV disease, but patients with AIDS are particularly at risk of severe complications of secondary infections. Patients with AIDS have a high risk of certain neoplastic diseases.
- The time-period for progression is the conventional measure used - from infection to manifestation of AIDS-related diseases.
- Five years after exposure, approximately 15% of patients will have progressed to AIDS - and of these, half will have died.
- Of the remaining 85% - less than one third will have constitutional symptoms of infection, less than two thirds will be completely asymptomatic and the remainder will only have lymphodenopathy.
Ten years after exposure - 50% will have progressed and deteriorated - of whom 80% will have died. Of the 50% who have not progressed to AIDS, one half will have constitutional symptoms - one third will have only lymphodenopathy and the rest will be asymptomatic with CD4+ counts ranging from >200 to 500.
Factors affecting progression of HIV to AIDS
Time taken for progression from HIV infection to AIDS may differ between individuals. This may be due in part to the presence of some of the following factors:
- Method of infection and the incubation period - may differ between those infected via blood and those infected via homosexual contact;
- The number of virus particles transferred;
- Simultaneous infection with other viruses or bacteria
- Infection with a strain of virus that is more virulent than others;
- Specific biochemical abnormalities, such as deficiency of the peptide glutathione;
- Age: In general, individuals over 30 years of age and young children develop AIDS faster than adolescents or young adults (possibly due to immune system variations);
- Genetic makeup;
- Behaviour (such as drug abuse) that suppresses the immune system.
Use of anti-viral therapy is proven to delay progression to AIDS.