Primary HIV Infection

Synonym: acute retroviral syndrome; seroconversion illness

Not everyone who has HIV experiences symptoms of a primary HIV seroconversion illness (range 53% to 93%). Incubation period is 2 to 4 weeks.

Of those who are seen in primary care with the illness, very few are correctly diagnosed.¹ If the diagnosis was made at such an early stage, benefits that may be assumed are:

• Early diagnosis should provide a better response to treatment.
• Treatment can be initiated before the immune system is severely damaged and opportunistic infections take hold.
• There will be less opportunity to spread the infection to others before the person's status is known.

Whilst the chance of early diagnosis may seem attractive, the reality is that early diagnosis is not often made and the disease is not usually diagnosed until the patient presents with opportunistic infections. Reasons for this include:

• The patient may not present to a doctor with the early illness.
• The signs and symptoms are so non-specific that it may easily be missed and the doctor may not know that the patient has a lifestyle that puts them at risk.
• It is easy to request a FBC and glandular fever screening test without much concern but HIV testing needs preliminary counselling, including confronting the patient with the potential diagnosis.

A constant awareness of this condition is required and the self-confidence to discuss it with the patient. The prevalence is rising but figures vary enormously with geography.

• The illness resembles glandular fever. It is associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption and thrombocytopenia.²
• The most specific of these features is a maculopapular rash affecting predominantly the upper part of the body and mucosal ulcers affecting the mouth and genital areas.
• A less common presentation is a predominantly gastrointestinal disease, including abdominal pain, nausea, vomiting, diarrhoea, hepatitis and even gastrointestinal haemorrhage.
• Rarer presentations include encephalopathy, pneumonitis and rhabdomyolysis associated with acute renal failure.
• It starts 2 to 6 weeks after exposure and usually resolves in a week or two, although it can take considerably longer.
• Those with more prolonged illness tend to have a poorer prognosis.³
• Acute, severe immunosuppression may occur during primary infection and AIDS-defining illnesses may also develop and should arouse suspicion of seroconversion in patients with a recent negative result on HIV testing.

The following table of relative frequency of symptoms is based on a paper from San Francisco.⁴

• Infectious mononucleosis caused by Epstein-Barr virus or cytomegalovirus.
• Toxoplasmosis.
• Rubella.
• Viral hepatitis, herpes simplex infection and other viral and spirochaetal illnesses.
• Acute onset Crohn's disease.
• Syphilis presenting with rash and mucocutaneous ulceration (rash is rare in cytomegalovirus, toxoplasmosis and Epstein-Barr virus patients who have not been given amoxicillin).

• If FBC shows low platelets this may suggest the diagnosis, although sensitivity and specificity are low.⁵
• When primary HIV infection is suspected, the essential tests are measurement of p24 antigen, which becomes detectable early after infection with HIV in many but not all cases, together with western blotting and the enzyme-linked immunosorbent assay (ELISA) antibody test.
• If suspicion is high and these tests give negative results, they should be repeated a few days later, together with direct viral identification using the polymerase chain reaction.
• Newer tests involving HIV-1 RNA and third generation enzyme immunoassay antibody tests capable of detecting IgM antibodies are becoming more popular.⁶
• Even in the early phases there is often a reduction in CD4 lymphocytes, a CD8 lymphocytosis and the ratio of CD4/CD8 is low.
• Mild anaemia, thrombocytopenia, abnormal LFTs and atypical lymphocytes may also be found.

HAART (highly active antiretroviral treatment) is extremely effective but there are risks and benefits to starting HAART in the primary disease.⁷

The management of HIV is complex and changing and should be undertaken by a specialist.The aim of antiretroviral therapy during acute HIV-1 infection is to reduce the number of infected cells, preserve HIV-1-specific immune responses and possibly lower the viral set point in the long-term. It is possible that once control has been achieved that the drugs can be stopped for a while with re-introduction if the viral load increases.⁸ Because of the uncertainty surrounding the management of the primary condition, patients should be asked to enter controlled trials.⁹

There is evidence that initiating early treatment may preserve normal immune function, suppress HIV viral replication, defer clinical progression and reduce HIV transmission.¹⁰ However, further trials are needed concerning the timing and duration of such treatment.¹¹ One study suggested that further work was needed to determine whether initial benefits were maintained in the long-term.¹² The challenges related to long-term management, include toxicity, adherence and drug resistance. The availability of superior new antiretroviral drugs and simplified regimens, the development of effective treatment strategies and further improvement of adherence through directly observed treatment are addressing the issues and changing the balance towards earlier treatment.¹³

The CD4+ count remains one of the best indications that anti-retroviral therapy is indicated; the trigger for treatment is generally to be taken to be a count of 350 cells per microL or lower.¹⁴

The primary disease is caused by viraemia and so it is unsurprising that those with a prolonged illness, being those who cope poorly with the viraemia, will have a poor prognosis. One study found that patients with more severe and numerous symptoms during primary HIV-1 infection had faster disease progression.⁶

The challenge in primary care is to make the diagnosis at an early stage when symptoms are so non-specific. Training in recognition of the symptoms of primary infection in clinicians providing care for patients with genito-urinary problems, including primary care professionals, would be helpful.¹⁵ Awareness is essential and a knowledge of the patient's lifestyle is also important. It is not easy to be able to discuss the possibility with the patient - with all the implications of the diagnosis - and it may well turn out to be negative. However, the opportunity to diagnose and treat HIV early is too important to miss. Early diagnosis does not just improve prognosis but may well reduce transmission in ignorance.

For the specialist, the challenge is to find the best regimen for the patient, getting the timing optimum and getting compliance from the patient. It is a complex matter and trials are still underway.