By Marissa van Hamersveld
Symptoms
As described previously in our article ‘What is the difference between HIV and AIDS?’, upon infection with HIV people may experience a variety of nonspecific ‘flu like’ symptoms or do not experience any complaints. Typically, the symptoms occur within 4 weeks to several months after exposure. These flu like symptoms of fever, swollen lymph nodes, sore throat, rash, muscle aches, diarrhoea, headache and weight loss are called the acute retroviral syndrome1.
The diagnosis of HIV is often delayed, because people experiencing these complaints often do not visit their doctor or if they do the doctor does not initially suspect HIV. However, specific symptoms can help to discriminate from the flu or other more common viral infections. Among these are the prolonged duration of the sickness, mouth ulcers, nervous system problems and infections that usually do not occur in healthy individuals, like a fungal infection of the mouth. In addition, HIV testing should especially be considered in high risk populations or in individuals who recently had sexually transmitted infection (STI).
Importance
Early diagnosis is very important, because starting and adhering to antiretroviral therapy (ART) reduces the risk of further HIV transmission and reduces the size of the latent reservoir. The latent reservoir is the amount of HIV infected immune cells of an individual that are not replicating2. It is different from the active HIV that is present in blood and other body fluids which is replicating and capable of infecting new cells. Reducing the size of the reservoir is important for possible future therapies that might eradicate all HIV from the body and thereby result in a HIV cure.
Methods for diagnosis
The diagnosis of HIV can be made on the detection of the virus (RNA virological test), antigens and/or antibodies in the blood (Immunoassay)3.
RNA virological test
The virus itself is detected through RNA virological tests which can determine the viral load. This method is based on a polymerase chain reaction (PCR), which can amplify and detect part of the RNA that forms the HIV genome. If no HIV is present in the sample, no RNA will be amplified and thus the test will come out negative. Of all available tests, this test has the shortest window phase. This means the test is the first able to detect a HIV infection after an exposure. However RNA virological test is rarely used for diagnosis due to the high cost.
Immunoassay
In response to the presence of HIV in the blood, the body produces antibodies. Depending on the duration of infection, these will initially only be Immunoglobulin M (IgM) and/ later also Immunoglobulin G (IgG). These antibodies are present in the blood serum, which is the fluid of the blood without the blood cells and clotting factors. Seroconversion, the conversion from seronegativity to seropositivity, is described as the moment when the present levels of HIV specific antibodies become high enough to be detected in the serum. After seroconversion, antibodies can be detected using an immunoassay.
The first and second generation immunoassays could only detect IgG. Later, the tests became more sensitive and were also able to detect IgM (third generation) or IgM and the p24 antigen, the core protein of HIV (fourth generation).
The latest generation of immunoassays simultaneously tests for IgM, IgG and the p24 antigen and is hence called the combination test. This combination test is very sensitive and is therefore used for HIV screening in combination with a RNA virological test4.
In resource-limited settings, it might be that the RNA virological test and latest generation immunoassays are not available. In that case, the WHO recommends to use the most sensitive assay available5. Immunoassays can provide rapid results at a single visit and is strongly recommended in these settings in order to make sure adequate follow-up will take place after a positive test result.
Test results
When the combination test and RNA virological test resulted negative, meaning no HIV RNA, antigen or antibodies were detected, the chance of a HIV infection is extremely low. However, in case of very recent and/or high-risk exposures, repeated testing after six weeks (a combination test) or after 3 months (an antibody test) is advised because seroconversion might not yet have taken place. In the window phase, the phase after exposure until seroconversion, an individual might get a reassuring negative test result even though the individual is infected with HIV. Of course, also symptoms resembling acute retroviral syndrome or immune system failure are reason to test for HIV again2.
If the combination test comes back positive, the HIV diagnosis is confirmed. In case of use of previous generation immunoassays, an additional immunoassay is required. After diagnosis, additional testing for drug resistance and potential other STIs will be performed and ART, if possible partner notification and counselling will be initiated.
1 Braun et al. Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection. Clin Infect Dis. 2015
2 Cohen et al. Acute HIV-1 Infection. N Engl J Med. 2011
3 http://www.cdc.gov/hiv/pdf/HIVtestingAlgorithmRecommendation-Final.pdf
4 Chavez P, Wesolowski L, Patel P, et al. Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay. J Clin Virol 2011; 52 Suppl 1:S51.
5 World Health Organization. Consolidated guidelines on HIV testing services. July 2015