oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Synonym: acute retroviral syndrome; seroconversion illness
In 2009, a total of 6,630 persons (4,400 men and 2,230 women) were newly diagnosed with HIV in the UK. About two thirds of patients who acquired the infection heterosexually did so in the UK, whilst four out of five infections in men who had sex with men (MSM) were acquired in the UK. Research from the Health Protection Agency (HPA) suggests that one in six MSM and one in 16 heterosexuals acquired their infection four to five months before diagnosis. 29% of new diagnoses of HIV in 2010 were black Africans. The vast majority of these became infected through heterosexual sex in Africa. Black Africans tend to present late in the infection, suggesting that more could be done to encourage early testing.
Approximately 70% of people with HIV infection experience symptoms during seroconversion. The incubation period is one to three weeks.
Of those who are seen in primary care with the illness, very few are correctly diagnosed. If the diagnosis were 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 with the early illness to a doctor.
- The signs and symptoms are so nonspecific 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 FBC and glandular fever screening test without much concern but HIV testing needs preliminary counselling, including confronting the patient with the potential diagnosis.
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.
- 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 two to six 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.
- 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.
|Main symptoms of primary HIV infection|
|Loss of appetite||54%|
|Loss of more than 2.5 kg in weight||32%|
|Fever and rash||46%|
Tips on diagnosing primary HIV infection in primary care
The challenge in primary care is to make the diagnosis at an early stage when symptoms are so nonspecific. GPs are used to spotting serious pathology when it presents with minor symptoms in the early stages and should use this approach when considering HIV.
When raising the possibility with patients, GPs should:
- Explain in an open manner the clinical reasons why the diagnosis should be considered.
- Talk to the patient in a non-judgemental way.
- Reassure the patient about confidentiality.
It is clearly neither possible nor indeed appropriate for GPs to send every patient presenting with minor viral symptoms for an HIV test; however:
- When considering glandular fever, think about HIV as well.
- Consider the diagnosis in patients presenting with a blotchy rash on the trunk or oral or perianal ulcers.
- Bear in mind commensural infections which can occur when the CD4 count drops rapidly - eg oral candidiasis, shingles.
- Headache, meningism and diarrhoea can be less common presentations.
- Infectious mononucleosis caused by Epstein-Barr virus or cytomegalovirus (CMV).
- Viral hepatitis, herpes simplex infection and other viral and spirochaetal illnesses.
- Acute-onset Crohn's disease.
- Gonococcal infection.
- Syphilis presenting with rash and mucocutaneous ulceration (rash is rare in CMV, 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. Mild anaemia, atypical lymphocytes and abnormal LFTs may also be found.
- Testing should comply with the guidelines of the British HIV Association (BHIVA). Currently these recommend simultaneous HIV antibody and p24 antigen tests.
- If these tests are negative, they should be repeated if suspicion is high. Confirmatory antibody and antigen RNA tests are available; the local laboratory will advise.
- Even in the early phases there is often a reduction in CD4 lymphocytes, a CD8 lymphocytosis and a ratio of CD4/CD8 which is low.
The management of primary HIV infection remains controversial. Although some data suggest possible immunological, virological, or clinical benefit of early treatment, other studies show no difference in these outcomes over time, after early treatment is discontinued. Large randomised trials are required to complement the existing evidence base which is supported by small non-randomised studies.
The CD4+ count remains one of the best indications that antiretroviral therapy is indicated; the trigger for treatment is generally to be taken to be a count of 350 cells per μL or lower.
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.
Further reading & references
- Atfelt M, Walker BD, Acute HIV-1 Infection, HIV Medicine
- Daskalakis D; HIV diagnostic testing: evolving technology and testing strategies. Top Antivir Med. 2011 Feb-Mar;19(1):18-22.
- HIV in Primary Care; Medical Foundation for AIDS & Sexual Health (2011)
- HIV in the United Kingdom - synopsis, Health Protection Agency, 2010
- HIV and AIDS in the UK, AVERT, 2012
- Carpenter R et al, Early Symptomatic HIV Infection, Medscape, Aug 2011
- Truong H et al, What is the role of acute HIV infection in HIV prevention?, Center for AIDS Prevention Studies at the University of California San Franciso, 2006
- Sudarshi D, Pao D, Murphy G, et al; Missed opportunities for diagnosing primary HIV infection. Sex Transm Infect. 2008 Feb;84(1):14-6. Epub 2007 Oct 30.
- Fox J, Weber J, Fidler S; Primary HIV. Sex Transm Infect. 2006 Aug;82(4):267-8.
- Hecht FM, Busch MP, Rawal B, et al; Use of laboratory tests and clinical symptoms for identification of primary HIV infection.; AIDS. 2002 May 24;16(8):1119-29.
- UK national guidelines for HIV testing, British HIV Association (September 2008)
- Bell SK, Little SJ, Rosenberg ES; Clinical management of acute HIV infection: best practice remains unknown. J Infect Dis. 2010 Oct 15;202 Suppl 2:S278-88.
- Gallant JE; When to start antiretroviral therapy: a swinging pendulum? Top HIV Med. 2008 Jun-Jul;16(2):82-8.
- Daar ES, Pilcher CD, Hecht FM; Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS. 2008 Jan;3(1):10-15.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Laurence Knott
Dr Laurence Knott
Dr John Cox