What is it?
Human immunodeficiency virus (HIV) seroconversion illness - also known as the acute primary HIV infection syndrome - is the initial manifestation of HIV infection. The clinical features associated with this syndrome were first described in Australia in 1985. It is generally self-limited illness with spontaneous recovery. If the illness is not diagnosed during this stage, the vast majority of them will remain well and asymptomatic for many years although rapid progression to AIDS has been described.

When does it occur?
The onset of the illness ranges from one to six weeks after exposure to the virus, e.g. through a sexual contact or sharing of HIV-contaminated needles. In some instances, however, it may be delayed for several months.

How often does it occur?
It has been shown in several studies that from one-half to two-thirds of recently infected individuals will develop this syndrome. Many will seek medical attention, but the illness is often attributed to a flu attack or benign viral fever. In Singapore, only about 10 individuals are diagnosed at or soon after seroconversion illness.

Why does it occur?
The acute primary illness resembles any other acute viral infection - after exposure to the virus, there is a burst of viral replication followed by a vigorous and appropriate immune response. It is this initial viral replication and immune response that results in the clinical and biochemical manifestations of the seroconversion illness. The amount of virus in the bloodstream is very high, and the risk of transmission is correspondingly greatest during seroconversion.

Some weeks to months later, the amount of virus in the bloodstream decreases as the body's defence mechanisms (the immune response) start clearing the virus. Under very rare circumstances, the virus may be eliminated entirely from the body. In the great majority of cases, though, the remnant virus persists and multiples in the lymphoid tissue (leading to swelling of lymph nodes). Progressive destruction of CD4+ lymphocytes (the white blood cells responsible of our immunity against infections) eventually cause the profound immunosuppression which is characteristic of HIV disease.

What are the features of HIV seroconversion illness?
The clinical symptoms and signs of primary infection are protean. It usually presents as a combination of the more common features, which include:
- fever
- lymphadenopathy (lymph node enlargement)
- rash
- myalgia (muscle aches)
- headache
- pharyngitis (sore throat)
- diarrhoea
Rarer presentations include oral and genital ulcers, altered mental state (encephalopathy), and impaired sensation of toes and fingers (peripheral neuropathy). Even ascending, rapidly progressive weakness of the limbs (Guillain-Barre-like syndrome) has been described.

As can be seen, the manifestations of this illness are rather non-specific, and may resemble any number of other viral illnesses. In fact, it was first described as a "mononucleosis-like" syndrome because of its resemblance to infectious mononucleosis, which is a condition caused by another far more benign virus - the Epstein-Barr virus.

However, the seroconversion illness usually lasts longer than the more common viral illnesses, extending more than a week in duration. Of special note is the fact that rhinitis (running nose), which is common in most viral illnesses is absent here.

How can it be distinguished from other infections?
The differential diagnosis for HIV seroconversion illness is very wide. It includes other viral illnesses such as influenza, Epstein-Barr virus infection, hepatitis, as well as other infections such as syphilis and toxoplasmosis.

In short, although various studies have pointed out unique features of the syndrome, it is impossible to be one hundred percent sure of the diagnosis.

The key point is that a high index of suspicion is required of both medical personnel as well as individuals with high-risk behaviour or professions.

How about blood tests?
Unfortunately, the HIV-screening test tends to be non-reactive, and even if it did turn out positive, the confirmatory Western Blot will be negative or indeterminate. The only way to confirm infection at the point of the seroconversion illness would be to test for the presence of the virus itself. This test is, however, expensive and not routinely done.

In individuals for whom HIV seroconversion illness is likely, it is important that the HIV-screening test should be repeated two to six months later. By then, the various HIV diagnostic tests will be positive if the individual actually has HIV infection.

Why bother about the HIV seroconversion illness?
It is important to diagnose this condition for the following reasons:
- It represents the earliest opportunity for the diagnosis of HIV infection.
- Early diagnosis of HIV infection allows for closer monitoring and intervention before the onset of opportunistic infections and clinical AIDS.
- It would also certainly help to prevent the further spread of HIV in the population, as the affected individual can be effectively counselled and educated about his condition at an earlier point in time.
- Several studies have demonstrated that HIV- infected individuals who develop the seroconversion illness tend to progress more rapidly to full-blown AIDS.
- Diagnosing HIV infection at this stage opens a window of opportunity towards early treatment of the infection as well as to possible elimination of the virus. The early results of some studies have been encouraging in this respect.

Reference
Lindback S, Thorstensson R, Karlsson AC, et al. Diagnosis of Primary HIV-1 Infection and duration of Follow-up after HIV Exposure. AIDS 2000, 14:2333-2339.

Lindback S, Brostrom C, Karlsson A, et al. Does symptomatic primary HIV-1 infection accelerate progresion to CDC stage IV disease, CD4 count below 200x 10(6)/L, AIDS, and death from AIDS? British Medical Journal 1994, 309:1535-1537.

De Loes SK, de Saussure P, Saurat JH, et al. Symptomatic Primary Infection due to HIV-1: Review of 31 Cases. Clinical Infectious Diseases 1993, 17:59-65.

Boyle MJ, McMurchie M, Tindall B, et al. HIV Seroconversion Illness. The Medical Journal of Australia 1993, 158:42-45