Early diagnosis of an acute HIV infection in a primary care setting : the opportunity for early treatment and prevention

Introduction Despite the fact that today over 40 million individuals worldwide are living with HIV, fewer than 1,000 cases have been diagnosed in the first month of infection [1]. Due to clinical reasons (acute retroviral syndromes mimic many common febrile illnesses) and because confirmatory HIV antibody tests will typically remain negative during the diagnostic window beyond the onset of acute retroviral symptoms, acute HIV infections are still missed [2, 3].


Introduction
Despite the fact that today over 40 million individuals worldwide are living with HIV, fewer than 1,000 cases have been diagnosed in the first month of infection [1].
Due to clinical reasons (acute retroviral syndromes mimic many common febrile illnesses) and because confirmatory HIV antibody tests will typically remain negative during the diagnostic window beyond the onset of acute retroviral symptoms, acute HIV infections are still missed [2,3].

Case report
In May, 2005, a 54-year-old man, who had recently returned from a vacation in Cuba, presented to us with high fever (39.8 °C), tonsillopharyngitis, fatigue and myalgia of one week's duration.No rash or lymphadenopathy were observed.At that point in time a lymphopenia (0.58 ҂10 3 cells/ mL), a thrombocytopenia (65 ҂ 10 3 cells/mL) and elevated C-reactive protein (64/5) were encountered.Slightly elevated liver enzymes were noted (alanine aminotransferase 41.8; aspartate aminotransferase 56.7; alkaline phosphatase 174; gamma-GT 104 and total bilirubin 45.5 mmol/L).
Malaria, dengue, Streptococcus pyogenes group A, enteroviruses, Shigella, Salmonella, Epstein-Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C virus and Treponema pallidum were excluded as causes of this clinical condition.
In the history at that time the patient denied any risk exposure known to be associated with HIV transmission.
Nevertheless, because of the lymphopenia and thrombocytopenia, an HIV screening test was suggested and the patient agreed.A third-generation HIV test gave a negative result and two fourth-generation HIV EIA Tests, which simultaneously detect antigen and antibodies, were reactive.A negative immunoblot test result was received from an external, designated confirmatory laboratory and a control testing in 3-6 months was suggested by them.In spite of this, we performed an HIV nucleic acid amplification test (NAT) on the first sample, which revealed a positive HIV-1 result of 4,150,000 copies/mL.Follow-up results are summarized in table 1.
At that point the patient confirmed an unprotected heterosexual contact on May 11 during his vacation in Cuba.

Discussion and conclusions
Many countries have recently placed significant emphasis on the identification of people with acute HIV infection [1,[4][5][6].
In our case we have shown that an early HIV infection can still be missed, in spite of clinical suspicion, by using immunoblot as the sole confirmatory method in patients with an early HIV infection in whom only the HIV antigen is detectable and antibodies have not yet been produced [5,7,8].
We can conclude that, in cases of leucopenia with thrombocytopenia and fever, an acute HIV infection has to be considered as the differential diagnosis and should be excluded.
For the diagnosis of an early HIV infection, fourth-generation EIA should replace the third-generation and NAT for HIV should be introduced into the confirmatory algorithm at the first sample stage in addition to the standard HIV fourth-generation EIA if the confirmatory immunoblot is negative.
In patients with reactive fourth-generation HIV EIA, with or without clinical illness, a negative immunoblot result should be followed by NAT.
This would optimise early HIV diagnosis without a significant cost increase, considering the benefits accruing in terms of opportunities for earlier treatment, source identification and introduction of preventive measures.

Letter to the editor 33 Original article 33 Letter to the editor
* cut off 1.0 ** cut off 0.25