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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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Chancellor insists Labour rebels ‘know the welfare system needs reform’ as they push for change

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Chancellor insists Labour rebels 'know the welfare system needs reform' as they push for change

Chancellor Rachel Reeves has insisted that rebelling Labour MPs “know the welfare system needs reform” as the government faces a growing backlash over planned cuts.

Sir Keir Starmer is under pressure from Labour MPs, with about 40 in the Red Wall – the party’s traditional heartlands in the north of England – warning the prime minister’s welfare plan is “impossible to support” in its current form.

Dozens have thrown their support behind a letter urging the government to “delay” the proposals, which they blasted as “the biggest attack on the welfare state” since Tory austerity.

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Ms Reeves on Friday reiterated her plans for reform, insisting that no-one, including Labour MPs and party members, “thinks that the current welfare system created by the Conservative Party is working today”.

She said: “They know that the system needs reform. We do need to reform how the welfare system works if we’re going to grow our economy.”

But, the chancellor added, if the government is going to lift people out of poverty “the focus has got to be on supporting people into work”.

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“Of course if you can’t work, the welfare state must always be there for you, and with this government it will be,” she said.

The reforms, announced ahead of Ms Reeves’s spring statement in March, include cuts to Personal Independence Payments (PIP), one of the main types of disability benefit, and a hike in the universal credit standard allowance.

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Starmer faces rebellion from Labour MPs over welfare reforms

The government has claimed that changes to welfare will cut the budget by £4.8bn overall.

Separately, Downing Street refused on Friday to deny that Ms Reeves has consulted on potentially overhauling their winter fuel payment policy.

Labour’s unpopular decision to means-test the policy has taken the benefit away from millions of pensioners.

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Ministers have faced pressure from their own backbenchers to rethink the policy in the wake of last week’s local election results, which saw Labour lose the Runcorn by-election and control of Doncaster Council to Reform UK.

Asked if the chancellor has discussed the winter fuel payment in private, the prime minister’s spokesperson said they would not give a running commentary.

Pushed again, Number 10 said a “range” of discussions take place in government – which is not a denial.

However, it is worth noting that when reports emerged earlier this week that Downing Street was reviewing the policy, the government strongly pushed back on that suggestion.

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Ten explosions near international airport in India-administered part of Kashmir, officials say

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Ten explosions near international airport in India-administered part of Kashmir, officials say

Ten explosions have been heard near Srinagar International Airport in India-administered parts of Kashmir, officials have told Reuters news agency.

The blasts followed blackouts caused by multiple projectiles, which were seen in the sky above the city of Jammu earlier on Friday.

Explosions were also heard in the Sikh holy city of Amritsar, in the neighbouring Punjab state, according to Reuters.

An Indian military official told the agency that “drones have been sighted” and “they are being engaged”.

It comes as tensions between India and Pakistan across the line of control around the region of Kashmir have boiled over this week, leading to fears of a wider conflict.

Map of where explosions were reported in Kashmir and from where

On Wednesday morning, India carried out missile strikes in Pakistan and Pakistan-administered parts of the disputed region.

The retaliation came weeks after 26 people, mainly Indian tourists, were shot dead by gunmen in an India-administered part of Kashmir last month.

The government in India said it hit nine “terrorist infrastructure” sites, while Pakistan said it was not involved in the April attack and the sites were not militant bases.

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Explained: India-Pakistan conflict

Around 48 people have been killed since Wednesday, according to casualty estimates on both sides – which have not been independently verified.

India also suspended its top cricket tournament, the Indian Premier League, as a result of rising tensions, while the Pakistan Super League moved the remainder of its season to the United Arab Emirates.

Meanwhile, White House press secretary Karoline Leavitt said at a conference on Friday that the US is in constant contact with both India and Pakistan.

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Russia’s Victory Day parade felt more like a celebration of war than peace

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Russia's Victory Day parade felt more like a celebration of war than peace

Standing on Red Square, this was an intimidating sight, which felt much more like a celebration of war rather than peace.

I could feel the ground shake as the tanks rolled past, their caterpillar tracks on the ancient cobbles providing a deafening clatter.

The hairs on the back of my neck stood up in fear as the phalanxes of troops roared “Hurrah” in response to their commander in chief.

And the sight of combat drones being paraded on their launchers was actually quite sickening. Weapons that have been at the forefront of Russia’s invasion of Ukraine were paraded in a show of pomp and patriotism.

Russian President Vladimir Putin and his Chinese counterpart Xi Jinping
Image:
Xi Jinping and Vladimir Putin watch the procession. Pic: Reuters

Ukraine war latest: Putin welcomes Xi at Victory Day parade

For the rest of Europe, the 80th anniversary of the end of the Second World War has been a celebration of peace, but this felt much more like a celebration of war.

And it wasn’t just military hardware on display here, but the very identity of modern Russia.

A general view shows Red Square during a military parade on Victory Day, marking the 80th anniversary of the victory over Nazi Germany in World War Two, in central Moscow, Russia, May 9, 2025. Vladimir Astapkovich/Host agency RIA Novosti/Handout via REUTERS ATTENTION EDITORS - THIS IMAGE WAS PROVIDED BY A THIRD PARTY.
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Pic: Reuters

For this is a country that is now defined by its military and its memory. The glory and sacrifice of 1945 have been weaponised to give credence to Russia’s current course and to make people believe that victory is their right.

For Russians, it served as a rallying cry and there was applause when the troops who have fought against Ukraine marched past.

But for those watching in Kyiv and other European capitals, it was an overt warning that Moscow has no intention of backing down.

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Putin hails sacrifice of Russian troops

The parade was considerably larger in scale than in recent years, when units and hardware have been needed on the battlefield. I think it was a deliberate attempt to project an image of confidence, and so was Vladimir Putin‘s positioning of his guests.

China’s Xi Jinping was given a prime position on the Kremlin leader’s right-hand side. It was no surprise given the economic lifeline Beijing has provided, but it felt like a particularly pointed gesture to the West – that they were looking at a new world order.

Despite that appearance of confidence, there were signs of Moscow’s unease that the parade could be disrupted.

There were snipers on every rooftop. Security was extremely tight. And the mobile internet signal across the city centre was completely shut down for fear of Ukrainian drone attacks, meaning none of the international media that had gathered could broadcast any live transmissions.

After the parade finished, Putin saluted the crowds as they spontaneously erupted into rhythmic shouts of “Rus-si-ya” at the sight of him.

Another PR coup complete without interruption, he will have departed as a very happy man.

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