Primary HIV Infection

Synonym: Acute retroviral syndrome; seroconversion illness

About 80 to 90% of patients who have been infected with HIV develop a primary illness 2 to 4 weeks later. 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. Reason 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 him 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.

Not everyone who has HIV experiences a primary HIV complex. Estimates of the frequency in homosexual men who have recently undergone seroconversion range from 53% to 93%. In many cases the condition is not recognised.

• 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 is the main differential diagnosis with a rash and mucocutaneous ulceration. This is rare in Epstein-Barr virus disease, cytomegalovirus, and toxoplasmosis unless the patient with Epstein Barr infection has been given amoxycillin.

• 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.
• 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.⁶

The assumption that it will improve prognosis is not fully supported. It may be that to start therapy too soon will confer no benefit but may lead to the development of drug resistance. On the other hand, if therapy is delayed too long, the disease is more advanced and the immune system more damaged.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

The literature is controversial about the optimal time to initiate therapy for HIV. There is evidence that initiating early treatment might provide benefits by treating primary HIV infection, preserving normal immune function, suppressing HIV viral replication, deferring clinical progression, and reducing HIV transmission. 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.¹⁰

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.

The challenge in primary care is to make the diagnosis at an early stage when symptoms are so non-specific. 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.