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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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Everyone in UK ‘must step up’ to deter Russian threat of wider war, armed forces chief to warn

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Everyone in UK 'must step up' to deter Russian threat of wider war, armed forces chief to warn

The whole of the UK – not just its armed forces – needs to step up to deter the threat posed by Russia of a wider war in Europe, Britain’s military chief will say.

In the kind of nation-wide call to action that has not been heard since the height of the Cold War, Air Chief Marshal Sir Richard Knighton will use a speech in London on Monday evening to urge the British public to make defence and resilience “a higher priority”.

He will say Russia’s war in Ukraine shows that Vladimir Putin’s willingness to target his neighbours “threatens the whole of NATO, including the UK. The Russian leadership has made clear that it wishes to challenge, limit, divide and ultimately destroy NATO”.

Yet there was nothing in excerpts of the speech – released in advance by the Ministry of Defence – that pointed to any push by Sir Keir Starmer’s government to increase defence spending faster than planned, despite the flashing warning signs and concerns among senior military officers that the budget is currently set to grow too slowly.

In a further articulation of the threat, Blaise Metreweli, the new head of MI6, will use a separate speech on Monday to warn that the “front line is everywhere” in a new “age of uncertainty”.

“The export of chaos is a feature not a bug in the Russian approach to international engagement,” she will say, in her first public comments since becoming the first female chief of the Secret Intelligence Service in October.

“We should be ready for this to continue until Putin is forced to change his calculus.”

More on Mi6

Read more:
Head of MI6: ‘Never seen the world in a more dangerous state’
NATO chief calls for 400% increase in air and missile defence

Defence and security chiefs across the NATO alliance are increasingly sounding the alarm about the potential for Russia’s war in Ukraine to ignite a much wider conflict.

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NATO ‘must prepare for scale of war our grandparents faced’, warns chief Mark Rutte

Mark Rutte, the head of NATO, last week said Europe must ready itself for a confrontation with Russia on the kind of scale “our grandparents and great-grandparents endured” – a reference to the First and Second World Wars.

At the same time, Al Carns, the UK’s armed forces minister, said Britain is “rapidly developing” plans to ready the entire country for the possible outbreak of war.

Sky News revealed last year that the UK had no national plan for the defence of the country or the mobilisation of its people.

By contrast, a detailed blueprint for the transition from a state of peace to one of war existed throughout the Cold War, setting out not just what the armed forces, emergency services and local governments had to do in the event of conflict, but also wider society, including people working in industry, schools and public transport.

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‘New era’ of threats from Russia, China and Iran

However, this Government War Book was quietly shelved after the Soviet Union collapsed and successive governments took a so-called “peace dividend”, shifting investment out of defence and into other priorities such as health and welfare.

Sky News and Tortoise have documented the hollowing out of the UK’s armed forces and wider national resilience in a podcast series called The Wargame.

The expected comments by Air Chief Marshal Knighton in an annual lecture at the Royal United Services Institute (RUSI) appear to signal an attempt by the government to put the country back on more of a war footing in the face of rising threats.

But military insiders have warned that a timeline set out by the government of 10 years to boost defence spending to 3.5% of GDP from 2.3% is far too slow.

👉 Click here to listen to The Wargame on your podcast app 👈

The chief of the defence staff will say: “The situation is more dangerous than I have known during my career and the response requires more than simply strengthening our armed forces. A new era for defence doesn’t just mean our military and government stepping up – as we are – it means our whole nation stepping up.”

He will nod to the planned uplift in spending, noting “the price of peace is increasing”.

He is set to say: “The war in Ukraine shows that Putin’s willingness to target neighbouring states, including their civilian populations, potentially with such novel and destructive weapons, threatens the whole of NATO, including the UK.”

This is a threat that wider society needs to prepare for as well as the military.

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Military analyst Sean Bell looks at the threat Russia poses

“Our armed forces always need to be ready to fight and win – that’s why readiness is such a priority,” Air Chief Marshal Knighton will say.

“But deterrence is also about our resilience to these threats, it’s about how we harness all our national power, from universities, to industry, the rail network to the NHS. It’s about our defence and resilience being a higher national priority for all of us. An ‘all-in’ mentality.”

It is a highly unusual intervention that has echoes of the Cold War when the UK last involved all of society in a programme of national defence and resilience against the threat of World War Three and potential nuclear Armageddon posed by the then Soviet Union.

“We are heading into uncertainty, and that uncertainty is becoming more profound, both as our adversaries become more capable and unpredictable, and as unprecedented technology change manifests itself,” Air Chief Marshal Knighton will say.

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Hughes scores in winning Wild debut after trade

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Hughes scores in winning Wild debut after trade

ST. PAUL, Minn. — Quinn Hughes scored in his Minnesota debut and the Wild beat the Boston Bruins 6-2 on Sunday for their fourth straight win.

Kirill Kaprizov had two goals and an assist for the Wild, who improved to 16-3-2 since Nov. 1, including 10-0-2 at home.

Ryan Hartman had a goal and two assists, Matt Boldy had a goal and an assist and Jared Spurgeon also scored for Minnesota. Filip Gustavsson made 29 saves, improving to 6-1-1 with a 1.84 goals-against average and .931 save percentage in his past eight starts.

Alex Steeves and Andrew Peeke scored, and Jeremy Swayman made 25 saves for Boston.

Playing his first game with the Wild after being acquired in a blockbuster trade with Vancouver on Friday, Hughes took a drop pass from Hartman in the opening minute of the third period and put a low wrist shot between Swayman’s pads to make it 4-0.

Hughes, who led all defensemen with 92 points in 2023-24, was paired with Brock Faber on Minnesota’s top blue-line pair and quarterbacked the first power-play unit. Faber had two assists.

Spurgeon scored his first goal in 30 games when his wrist shot found its way through traffic for a power-play tally midway through the first period for a 1-0 lead.

Midway through the second period, Kaprizov doubled the Wild lead thanks to a fortuitous carom. Boldy’s shot was deflected by a defenseman but quickly ricocheted off the end boards to Kaprizov who tucked the puck past Swayman at the right post.

Faber split a pair of defenders and fed Hartman for an easy redirect less than four minutes later for the Wild’s second power-play tally.

Boldy made it 5-0 before Steeves scored off a scramble midway through the third period. Kaprizov made it 6-1 with his 20th of the season with 5:05 remaining, and Peeke scored in the final second of the third period.

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Canucks’ Buium: Not misled by Wild before trade

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Canucks' Buium: Not misled by Wild before trade

NEWARK, N.J. — Zeev Buium was the Minnesota Wild‘s defenseman of the future until they made him the centerpiece of the Quinn Hughes trade last Friday, shipping the 20-year-old in a package to the Vancouver Canucks for their star captain.

Buium said he doesn’t feel he was misled about his status with the Wild before the trade.

“I don’t think anything they told me was a lie. I really don’t,” Buium said Sunday after the Canucks’ 2-1 road victory over the New Jersey Devils. “[Wild GM] Bill Guerin is an unbelievable person. He’s such a smart guy. He wants to try and win now, and that’s a move he thought was best for the team. At the end of the day, you have to do what’s best for the team.”

Buium was traded to Vancouver along with center Marco Rossi, winger Liam Ohgren and a 2026 first-round pick for Hughes, the 26-year-old Norris Trophy winner who is considered one of the best defensemen in hockey. Hughes had 432 points in 459 games heading into Sunday’s action and was the leading scorer on Vancouver (23 points in 26 games) before Friday’s blockbuster trade.

Buium had two points in his debut with the Canucks, both on the power play. He earned an assist on Jake DeBrusk‘s opening goal and then was credited with his fourth goal of the season when his pass deflected off the stick of Devils defenseman Brenden Dillon.

He was drafted 12th overall in 2024 by the Wild and was an offensive dynamo with the University of Denver for two seasons (98 points in 83 games). He had 14 points in 31 games as a rookie this season before the trade.

Guerin called Buium a “special kid and a special human,” but he indicated that the Wild’s bid for Hughes was only successful because Buium was a part of it.

“I love that kid, but you have to give something to get something,” Guerin said.

Buium didn’t take the trade personally, but he said he’ll use it as motivation.

“I don’t think it’s [Guerin] saying, ‘You’re not good enough’ or ‘We don’t believe in you.’ But I think he sees me needing to develop a little bit more,” Buium said. “I think it works out for both teams. I’m going to do my best to show the Canucks that they made a good trade. Hopefully, I can turn into a player like that.”

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