HIV AIDS diagnostic study of choice
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kanwal Khamuani
Overview
In 1980s, AIDS was first recognized and used to be diagnosed with simple serologic testings that detected HIV antibodies using culture derived viral antigen preparations. Later on with passing time, various serological assays were developed that used different testing formats, antigen designs and signal detection amplification chemistries assessing their testing accuracy to ensure that the patient is correctly diagnosed and followed with health care services. This spectrum of testing include Rapid testing, Screening assays and Supplementary confirmation tests that have proven to be beneficial in reducing testing times and improving health care delivery in resource limited settings. Determining the most appropriate test for a given case is largely based on the natural history of HIV infection (i.e., the marker that is detected at a given point after having the infection).
Diagnostic Study of Choice
Study of choice
- Fourth generation test(ELISA/ELI/MEIA/ELFA/ECLIA) have high sensitivity; therefore they are used as confirmatory test. These test can detect both p24 antigen as well as HIV antibodies. Neonates of HIV infected mothers are tested with PCR.[1]
- Determining the most appropriate test for a given case is largely based on the natural history of HIV infection (i.e., the marker that is detected at a given point after having infection):
| Days After Infection | The Most Appropriate Test |
|---|---|
| Prior to viremia which occurs at day 5, which is called the “eclipse period” | The HIV virus cannot be detected |
| 6 to 8 days after infection | Nucleic acid ampilification testing (NAAT) |
| 13 to 20 days after infection | p24 antigen |
| By day 20 | IgM antibodies |
| By day 30 | IgG antibodies |
- Patients often present late, when antibodies testing and NAAT are both positive.[2]
Screening Immunoassays
There have been five generations of enzyme immunoassays(EIAs) that use different [[antigen] compositions and detection chemistries to give precise and high volume samples for laboratories.[3]
- First Generation Assay: It used antigen lysate preparations to detect antibodies; however due to high false positivity it was replaced by highly specific immunoassays and western blot techniques.
- Second Generation Assay: Proteins derived from Immunodominant regions(IDR) of HIV-1 proteins and gp36 of HIV-2 were used to increase sensitivity and decrease false positivity.
- Third Generation Assay: Detection of Ig G antibodies by using antigens such as gp160 derived from HIV-1 group M, recombinant p24, recombinant peptide from HIV-2 gp36 IDR and synthetic peptide from HIV-1 group O. It also detected HIV-1 IgM to further reduce window period.
- Fourth Generation: It detected both antigen and antibodies at the same time using fully automated chemiluminescent microparticle.
- Fifth Generation: It used multiplex format to detect distinguished p24 antigen of HIV-1 and HIV-2.
Confirmatory Immunoassays
The specimens that were reactive with EIAs need to be retested with more specific confirmatory test which is Western Blot using a gradient purified HIV lysate, electrophorese and suffused onto nitrocellulose strips. For WB to be considered positive, it has to contain antibodies reactive to p24 antigen and envelope glycoproteins.[3]
Rapid Testing Assays
The rapid tests is completed in about 20-30 mins making it ideal in primary care and mobile clinics. Non-laboratory staff can perform these test as it require finger prick blood sample (<10 to 50 μl) or oral fluid. Although these are less sensitive than EIAs; however, their specificity is higher. [3]
Polymerase Chain Reaction
As newborns carry HIV antibodies from mother up to 15 months of age; therefore, antibody detection is not reliable in them. PCR detects the infection by amplifying the viral nucleic acid from a very small number of viral particles. Uncertain western blot results are confirmed with PCR and patients who are immunocompromised are also diagnosed with this highly specific and highly sensitive test.[1]
Sequence of Diagnostic Studies
The fourth generation assays(EIAs, RDTs, CLIAs, ECLs) are performed when HIV is suspected.[4]
- A reactive test is followed by confirmatory second assay from any other fourth generation test.
- A nonreactive test is reported as a negative HIV patient.
If a second line assay is positive:
- It is followed by a retesting prior to starting ART.
If a second line assay is negative:
- Both first line and second line assay are repeated.
Upon repetition if both test give same results as above:
- perform third line assay
Upon repetition if both are negative:
- It is reported as HIV negative patient or the test is repeated again if high risk features are present.
If results of third line are positive:
- patient is asked to be retested after 14 days
If results of third line assay are negative:
References
- ↑ 1.0 1.1 Zulfiqar HF, Javed A, Afroze B, Ali Q, Akbar K; et al. (2017). "HIV Diagnosis and Treatment through Advanced Technologies". Front Public Health. 5: 32. doi:10.3389/fpubh.2017.00032. PMC 5339269. PMID 28326304.
- ↑ Saag MS (2021). "HIV Infection - Screening, Diagnosis, and Treatment". N Engl J Med. 384 (22): 2131–2143. doi:10.1056/NEJMcp1915826. PMID 34077645 Check
|pmid=value (help). - ↑ 3.0 3.1 3.2 Parekh BS, Ou CY, Fonjungo PN, Kalou MB, Rottinghaus E, Puren A; et al. (2019). "Diagnosis of Human Immunodeficiency Virus Infection". Clin Microbiol Rev. 32 (1). doi:10.1128/CMR.00064-18. PMC 6302353. PMID 30487166.
- ↑ Fearon M (2005). "The laboratory diagnosis of HIV infections". Can J Infect Dis Med Microbiol. 16 (1): 26–30. doi:10.1155/2005/515063. PMC 2095005. PMID 18159524.