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By Dr. Priyom Bose, Ph.D. Reviewed by Danielle Ellis, B.Sc.

What happens after HIV infection?
Evolution of HIV diagnostic assays
Conclusions
References
Further reading

Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV) that attacks the body’s immune system, making it vulnerable to all infections. One of the major concerns of the early AIDS epidemic that began in 1981 was the lack of proper diagnostic measures to identify infected individuals.1 Since the development of the first HIV diagnostic assay in 1985, scientists have continued to improve diagnostic accuracy, detection speed, and cost.

Image Credit: Hanna Karpiak/Shutterstock.com What happens after HIV infection?

The immune system produces antibodies after encountering harmful foreign substances or antigens. HIV infects the vital cells associated with immunity, such as macrophages, helper T cells, and dendritic cells, and disrupts their function. The three important HIV antigens are p24, gp 41, and gp 120.2

HIV is a slow-replicating retrovirus that is transmitted through sexual intercourse, sharing an infected needle, or by blood transfer.3 After HIV infection, the viral load cannot be measured immediately due to low plasma load. Typically, the viral RNA can be measured within 10 to 12 days after infection.4

Antibodies to p24 and gp 41 are the first serological markers used to detect HIV infection. IgG antibodies appear approximately three weeks after infection. In the majority of HIV-infected individuals, HIV antibodies appear to circulate within 1 to 2 months of the infection. However, in a few cases, it may take up to six months to appear at a detectable level.5 Evolution of HIV diagnostic assays

Over the years, scientists have developed many immunoassays and nucleic acid amplification tests (NAATs) to accurately and high-throughput HIV diagnosis. These tests are broadly divided into two categories, namely, screening and confirmatory tests. Typically, HIV tests are performed on blood, oral fluids, or urine samples.6

HIV screening is performed by various immunoassays that focus on detecting IgG antibodies against HIV-1 antigens in the serum. Techniques such as Western blot, line immunoassay (LIA), and recombinant immunoblot are used as confirmatory tests.7 Some of the important HIV diagnostic assays are discussed below: Serological testing for HIV

In the mid-1980s, simple serological tests for HIV antibodies were developed based on culture-derived viral antigen preparation.7 These tests enabled HIV diagnosis and assessed blood and blood product supplies. Since the early assays, various serological assays have been developed that aided simple/rapid testing, high-throughput screening, confirmatory tests, incidence determination, and epidemiological surveillance. Since its first development, five generations of enzyme immunoassays (EIAs) have emerged based on varied antigen preparations and detection chemistries.8

First-generation assays: The first-generation EIAs detect IgG antibodies from antigens derived from whole viral lysates of HIV-positive cultures. Since crude antigen lysate contains impurities, this method exhibited reduced specificity and high false positivity. In contrast, immunofluorescence assays or Western blotting (WB) have shown higher specificity and lower false positivity.

Second-generation assays: Second-generation assays involve the use of recombinant proteins or synthetic peptides derived from the immunodominant regions (IDR) of HIV-1 proteins and gp36 of HIV-2, which increases sensitivity and decreases false positivity.

Third-generation assays: Third-generation assays, including the Genetic Systems HIV-1/HIV-2 Plus O EIA, use a variety of antigens to detect HIV-1 and -2 antibodies in the serum. A major advantage of third-generation sandwich format assays is their ability to detect HIV-1 IgM antibodies early, enabling quicker HIV diagnosis.

Fourth-generation assays: The fourth-generation EIAs, including the Abbott Architect HIV Ag/Ab Combo assay, utilize fully automated chemiluminescent microparticle technology that can instantaneously identify antibodies to HIV-1 and HIV-2 and HIV-1 p24 antigen. This technique has further allowed early HIV diagnosis. Other advantages of fourth-generation high-throughput assays are their capacity to perform more than 150 tests per hour and their ability to test specimens immediately upon arrival and generate results within 30 minutes.  These assays are suitable for facilities, such as blood banks, that handle high volumes of blood samples.

Fifth-generation assays: Fifth-generation assays, such as the Bio-Rad BioPlex 2200 HIV Ag-Ab assay, use magnetic beads coated with p24 monoclonal antibodies and epitopes specific for HIV-1 and HIV-2. This type of assay has a major advantage in  that it can confirm HIV infection in a single test. Interested in Assay Kits? Explore Equipment Here

Despite the advancements in EIA assays, the challenges associated with the generation of false positive results persist. Therefore, EIA-reactive specimen is typically retested with supplemental tests, such as Western Blot. Rapid diagnostic tests Related StoriesSweden exceeds UNAIDS HIV goals but faces new challengesNutrition's pivotal role in combating tuberculosis: addressing N-AIDS for better outcomes

The first HIV rapid test was available in the early 1990s. It determined an individual's serostatus before surgery, maternal labor/delivery, and organ transplant. Rapid diagnostics is based on immunochromatographic technology that uses blood from finger pricks to assess HIV status. 9 This test can provide results in less than 30 minutes and can be used in point-of-care (POC) settings. Since this test presents both false positive and negative results, it is essential to confirm the findings with laboratory-based HIV assays.

The main advantage of this technique is that any non-laboratory staff can perform it in a primary health care center. Even though decentralization of HIV diagnostic services has increased HIV test service in remote areas, it has been challenged by the lack of national guidelines, waste disposal, inventory management, and quality assurance (QA) monitoring.10

HIV self-testing, based on rapid testing methods, has allowed individuals who would otherwise refrain from testing in fear of discrimination to perform the test privately and start proper intervention. The World Health Organization (WHO) has prequalified several HIV rapid tests for HIV self-testing, including the Insti HIV-1/HIV-2 antibody tests and the Oraquick rapid HIV-1/2 antibody test.10 Nucleic acid test (NAT)

The NAT identifies HIV nucleic acid, i.e., either RNA or proviral DNA, in the blood sample. This test is based on the principles of polymerase chain reaction (PCR), nucleic acid sequence-based amplification, or ligase chain reaction.11 This test has proved to be vital in situations when an antibody against HIV is absent in serum. NAT is also performed in newborns of HIV-infected mothers. Unlike other assays, this test can detect HIV even after recent or possible exposure to the virus. Furthermore, NAT can quantify viral load.

Revolutions in Infectious Disease Testing Conclusions

The advancements in HIV diagnostic assays have played a vital role in identifying, staging, and monitoring infected individuals, even when they are under antiretroviral therapy. These assays have played an important role in surveillance and identification of transmission hot spots. Extraordinary progress in HIV testing methodologies has not only reduced false positives but decreased assessment time as well. References Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011;1(1):a006841. doi: 10.1101/cshperspect.a006841. Foster JE., et al. Viruses as Pathogens: Animal Viruses, With Emphasis on Human Viruses. Viruses. 2018; 157-187. doi.org/10.1016/B978-0-12-811257-1.00007-3 Dasgupta A, Wahed. Human immunodeficiency virus (HIV) and hepatitis testing. Clinical Chemistry, Immunology and Laboratory Quality Control (Second Edition). 2021; 513-533. doi.org/10.1016/B978-0-12-815960-6.00015-7 Konrad BP, et al. On the duration of the period between exposure to HIV and detectable infection. Epidemics. 2017; 20, 73-83. doi.org/10.1016/j.epidem.2017.03.002 Davis LE. Acute viral meningitis and encephalitis. Infections of the Nervous System, 1987; 156-176. doi.org/10.1016/B978-0-407-02293-5.50014-3 Pant PN. Oral fluid-based rapid HIV testing: issues, challenges and research directions. Expert Review of Molecular Diagnostics. 2007; 7 (4), 325-328, DOI: 10.1586/14737159.7.4.325 Abdullah DM, et al. The contemporary immunoassays for HIV diagnosis: a concise overview. Asian Biomed (Res Rev News). 2023;17(1):3-12. doi: 10.2478/abm-2023-0038. Alexander TS. Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution. Clin Vaccine Immunol. 2016;23(4):249-53. doi: 10.1128/CVI.00053-16. Aidoo S, et al. Suitability of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus in Ghana, West Africa. J Clin Microbiol. 2001;39(7):2572-5. doi: 10.1128/JCM.39.7.2572-2575.2001. Parekh BS, et al. Diagnosis of Human Immunodeficiency Virus Infection. Clin Microbiol Rev. 2018;32(1):e00064-18. doi: 10.1128/CMR.00064-18. Garrett, P. E. Quality control for nucleic acid tests: Common ground and special issues. Journal of Clinical Virology. 2001; 20(1-2), 15-21. doi.org/10.1016/S1386-6532(00)00150-5

Further ReadingAll HIV ContentThe Economic Impacts of AIDSRecent Advancements in Treating HIV

Last Updated: Nov 29, 2024

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Gillian Anderson warns UK homelessness ‘will only get worse’

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Gillian Anderson warns UK homelessness 'will only get worse'

Gillian Anderson has warned homelessness is a growing problem in the UK – one that will only get worse if we enter a recession.

The award-winning actress, who is playing a woman facing homelessness along with her husband in her latest film, The Salt Path, told Sky News: “It’s interesting because I feel like it’s even changed in the UK in the last little while.”

Born in Chicago, and now living in London, she explained: “I’m used to seeing it so much in Vancouver and California and other areas that I spent time. You don’t often see it as much in the UK.”

Her co-star in the film, White Lotus actor Jason Isaacs, chips in: “You do now.”

“It’s now becoming more and more prevalent since COVID,” said Anderson, “and the current financial situation in the country and around the world.

“It’s a topic that I think will be more and more in the forefront of people’s minds, particularly if we end up going into a recession.”

Pic: Steve Tanner/Black Bear
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Gillian Anderson and Jason Isaacs in The Salt Path. Pic: Steve Tanner/Black Bear

The film is based on Raynor Winn’s 2018 memoir, which depicts her and her husband’s 630-mile trek along the Cornish, Devon and Dorset coastline, walking from Minehead, Somerset to Land’s End.

Written from her notes on the journey, The Salt Path went on to sell over a million copies worldwide and spent nearly two years in The Sunday Times bestseller list. Winn’s since written two more memoirs.

Isaacs, who plays her husband Moth Winn in the movie, told Sky News that Winn told him she “hopes [the film] makes people look at homeless people when they walk by in a different light, give them a second look and maybe talk to them”.

With record levels of homelessness in the UK, with a recent Financial Times analysis showing one in every 200 households in the UK is experiencing homelessness, the cost of living crisis is worsening an already serious problem.

Pic: Steve Tanner/Black Bear
Image:
Pic: Steve Tanner/Black Bear

The film sees Ray and Winn let down by the system, first by the court which evicts them from their home, then by the council which tells them despite a terminal diagnosis they don’t qualify for emergency housing.

Following the loss of their family farm shortly after Moth’s shock terminal diagnosis with rare neurological condition Corticobasal Degeneration (CBD), the couple find solace in nature.

They set off with just a tent and two backpacks to walk the coastal path.

Isaacs says living in a transient way comes naturally to actors, admitting like his character, he too “lives out of a suitcase” and is “away on jobs often”.

Read more:
Is this every actor’s bucket list job?

Pic: Steve Tanner/Black Bear
Image:
Pic: Steve Tanner/Black Bear

Shot in 2023 across Somerset, Devon, Cornwall and Wales, Anderson says as a city-dweller, the locations had an impact on her.

Anderson reveals: “As I’ve gotten older, I have become more aware of nature than […] when I was younger, and certainly in filming this film and being outside and so much of nature being a third character, it did shift my thinking around it.”

Meanwhile, Isaacs says he discovered a “third character” leading the film just the day before our interview, when speaking to Winn on the phone.

Isaacs says the author told him: “I feel like there’s three characters in the film,” going on, “I thought she was going to say nature, but she said, ‘No, that path'”.

Isaacs elaborates: “Not just nature, but that path where the various biblical landscapes you get and the animals, they matter.

“The things that happen on that path were a huge part of their own personal story and hopefully the audience’s journey as well.”

The Salt Path comes to UK cinemas on Friday 30 May.

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PM could lift controversial benefit cap in budget – as Farage makes two big election promises

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PM could lift controversial benefit cap in budget - as Farage makes two big election promises

Sir Keir Starmer could decide to lift the two-child benefit cap in the autumn budget, amid further pressure from Nigel Farage to appeal to traditional Labour voters.

The Reform leader will use a speech this week to commit his party to scrapping the two-child cap, as well as reinstating winter fuel payments in full.

The prime minister – who took Westminster by surprise at PMQs by revealing his intention to row back on the winter fuel cut – has previously said he would like to lift the two-child cap if the government could afford it.

There are now mounting suggestions an easing of the controversial benefit restriction may be unveiled when the chancellor delivers the budget later this year.

According to The Observer, Sir Keir told cabinet ministers he wanted to axe the measure – and asked the Treasury to look for ways to fund the move.

It comes after the government delayed the release of its child poverty strategy, which is expected to recommend the divisive cap – introduced by former Tory chancellor George Osborne – is scrapped.

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Why did Labour delay their child poverty strategy?

Ministers have already said any changes to winter fuel payments, triggered by mounting political pressure, would only be made when the government’s next fiscal event rolls round.

The Financial Times reported it may be done by restoring the benefit to all pensioners, with the cash needed being clawed back from the wealthy through the tax system.

The payment was taken from more than 10 million pensioners this winter after it became means-tested, and its unpopularity was a big factor in Labour’s battering at recent elections.

Before Wednesday’s PMQs, the prime minister and chancellor had insisted there would be no U-turn.

More from Sky News:
PM’s winter fuel claim ‘not credible’
Starmer vs Reeves – the ‘rift’ in Downing Street

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Will winter fuel U-turn happen?

Many Labour MPs have called for the government to do more to help the poorest in society, amid mounting concern over the impact of wider benefit reforms.

Former prime minister Gordon Brown this week told Sky News the two-child cap was “pretty discriminatory” and could be scrapped by raising money through a tax on the gambling industry.

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Brown questioned over winter fuel U-turn

Mr Farage, who believes Reform UK can win the next election, will this week accuse Sir Keir of being “out of touch with working people”.

In a speech first reported by The Sunday Telegraph, he is expected to say: “It’s going to be these very same working people that will vote Reform at the next election and kick Labour out of government.”

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Sir Alan Bates attacks ‘kangaroo court’ Post Office scheme after ‘take it or leave it’ offer

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Sir Alan Bates attacks 'kangaroo court' Post Office scheme after 'take it or leave it' offer

Sir Alan Bates has accused the government of presiding over a “quasi kangaroo court” for Post Office compensation.

Writing in The Sunday Times, the campaigner, who led a years-long effort for justice for sub-postmasters, revealed he had been given a “take it or leave it” offer that was less than half of his original claim.

“The sub-postmaster compensation schemes have been turned into quasi-kangaroo courts in which the Department for Business and Trade sits in judgement of the claims and alters the goal posts as and when it chooses,” he said.

“Claims are, and have been, knocked back on the basis that legally you would not be able to make them, or that the parameters of the scheme do not extend to certain items.”

More than 900 sub-postmasters were prosecuted between 1999 and 2015 after faulty Horizon accounting software made it look as if money was missing from their accounts.

Many are still waiting for compensation despite the previous government saying those who had their convictions quashed were eligible for £600,000 payouts.

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‘It still gives me nightmares’

After the Post Office terminated his contract over a false shortfall in 2003, Sir Alan began seeking out other sub-postmasters and eventually took the Post Office to court.

More on Post Office Scandal

A group litigation order (GLO) scheme was set up to achieve redress for 555 claimants who took the Post Office to the High Court between 2017 and 2019.

Sir Alan, who was portrayed by actor Toby Jones in ITV drama Mr Bates Vs The Post Office, has called for an independent body to be created to deliver compensation.

He added that promises the compensation schemes would be “non-legalistic” had turned out to be “worthless”.

It is understood around 80% of postmasters in Sir Alan’s group have accepted a full and final redress, or been paid most of their offer.

Read more:
Post Office scandal explained

Who are the key figures in the scandal?

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‘Lives were destroyed’

A Department for Business and Trade spokesperson told Sky News: “We pay tribute to all the postmasters who’ve suffered from this scandal, including Sir Alan for his tireless campaign for justice, and we have quadrupled the total amount paid to postmasters since entering government.

“We recognise there will be an absence of evidence given the length of time which has passed, and we therefore aim to give the benefit of the doubt to postmasters as far as possible.

“Anyone unhappy with their offer can have their case reviewed by a panel of experts, which is independent of the government.”

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