Synonym: acute retroviral syndrome; seroconversion illness
In 2013, a total of 6,000 persons (4,500 men and 1,500 women) were newly diagnosed with HIV in the UK. The number of newly diagnosed heterosexual men and women has dropped over the years from 4,890 in 2004 to 2,490 in 2013) due to fewer diagnoses among people born in sub-Saharan Africa. 76% of infections in men who had sex with men (MSM) were acquired in the UK. One study suggested that 16% of people newly diagnosed in England, Wales and Northern Ireland acquired their infection 4-6 months before diagnosis. 19% of new diagnoses of HIV in 2012 were black Africans. Black Africans tend to present late in the infection, suggesting that more could be done to encourage early testing. Research in 2011 suggested that 48% of people born abroad are likely to have acquired infection in the UK. Approximately 70% of people with HIV infection experience symptoms during seroconversion. The incubation period is one to three weeks.
- 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 of HIV 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.
New diagnoses have been declining since they peaked in 2005, mainly due to a fall in the number of diagnoses reported among heterosexuals from high HIV prevalence countries.
- 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 kidney injury.
- 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 relative frequency of symptoms has been reported as follows:
|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.
Dr Hayley Willacy advises that recent guidelines are available concerning starting antiretroviral therapy (ART). Their advice is that ART should be initiated in all adults living with HIV, regardless of WHO clinical stage and at any CD4 cell count (strong recommendation, moderate-quality evidence). As a priority, ART should be initiated in all adults with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adults with CD4 count ≤350 cells/mm3 (strong recommendation, moderate-quality evidence).
Earlier initiation of ART results in reduced mortality, morbidity and HIV transmission outcomes. Increasing evidence from systematic reviews and cohort analyses also indicates that untreated HIV infection may be associated with the development of several non-AIDS-defining conditions, including cardiovascular, kidney and liver disease, several types of cancer and neurocognitive disorders and that initiating ART earlier reduces such events and improves survival.
The management of primary HIV infection remains controversial. UK guidelines recommend the following indications:
- Immediately after HIV diagnosis.
- Any AIDS-defining infection or major infection where the confirmed CD4 cell count is <200 cells/mL.
Controversy exists because 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. Evidence is emerging that treatment of acute HIV infection may have short-term benefit on viral set point when compared to delayed therapy as well as reducing the risk of transmission to others. Furthermore, studies suggest that use of relatively short-acting potent agents such as recombinant immunotoxins might prove sufficient for HIV eradication, obviating the need for long-term therapy.
The World Health Organization recommends a CD4 count threshold ≤500 cells per μL but this has yet to be adopted in the UK.
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 and 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-Mar19(1):18-22.
HIV in the United Kingdom: 2014 Report; Public Health England
HIV and AIDS in the UK; AVERT
HIV and Black African Communities in the UK; National Aids Trust, 2014
Primary HIV Infection: knowledge amongst gay men; National AIDS Trust, 2011
Sudarshi D, Pao D, Murphy G, et al; Missed opportunities for diagnosing primary HIV infection. Sex Transm Infect. 2008 Feb84(1):14-6. Epub 2007 Oct 30.
HIV in Primary Care; Medical Foundation for AIDS & Sexual Health (2011)
O'Brien M, Markowitz M; Should we treat acute HIV infection? Curr HIV/AIDS Rep. 2012 Jun9(2):101-10. doi: 10.1007/s11904-012-0113-0.
Fox J, Weber J, Fidler S; Primary HIV. Sex Transm Infect. 2006 Aug82(4):267-8.
Hoffmann C et al; Acute HIV-1 Infection, hivbook.com, 2011.
Dubrow R, Sikkema KJ, Mayer KH, et al; Diagnosis of acute HIV infection in Connecticut. Conn Med. 2009 Jun-Jul73(6):325-31.
UK national guidelines for HIV testing; British HIV Association (September 2008)
Guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy; British HIV Association (2015)
Dey B, Berger EA; Toward an HIV cure based on targeted killing of infected cells: different approaches against acute versus chronic infection. Curr Opin HIV AIDS. 2015 Feb 23.
Daar ES, Pilcher CD, Hecht FM; Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS. 2008 Jan3(1):10-15.