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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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Not afraid to write to Putin, grieving mother demands explanation after teenage conscript killed

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Not afraid to write to Putin, grieving mother demands explanation after teenage conscript killed

In her desperate search for answers over her son Valentin’s death, Elena even turned to Vladimir Putin.

She wrote to the Russian president demanding an explanation as to why an 18-year-old conscript was involved in combat.

Throughout the war in Ukraine, the Kremlin promised that conscripts wouldn’t be sent to war. But in Valentin’s case, the war came to him.

Valentin in combat gear
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Valentin, 18, died nearly a year into his military service

He had been deployed to the Kursk region as part of his military service and stationed on the border.

But it was there that Ukrainian forces launched their cross-border incursion in August and one month after it began, Valentin was killed after receiving a shrapnel wound to the head.

“It should be specially trained people there, not children,” Elena says.

“They were taken from home, from a mother’s nest, and brought to some unknown place, where there is shooting.

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“What kind of warrior is he? He’s not a warrior.”

Valentin's grave
Image:
Valentin’s grave

Like other fallen soldiers, Russia views Valentin as a hero, but that’s no comfort to Elena. All she has are questions, which she wasn’t afraid to put to Mr Putin directly.

“The most important question was: ‘What were our children doing there?’ But I didn’t get any response,” she says.

“At that moment I just wanted to take the whole world and turn it upside down.

“Whoever says they are obligated for military service, what do they owe? What did my son take from the Motherland to pay a debt with his life?”

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Valentin was a few weeks short of his 19th birthday when he died, and nearly a year into his military service. Elena didn’t want him to sign on so soon – head boy at school, he could have deferred conscription until after further study – but she says he was excited to serve and insisted.

Pictures of him in his parade uniform are everywhere in her apartment in Rybinsk, a town 160 miles northeast of Moscow. His blue beret is perched on a shelf. And Elena still hopes that one day he’ll walk through the door.

Elena's son Valentin
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Valentin, who had been head boy at school, was keen to serve

The graveyard Valentin is buried in
Image:
The graveyard Valentin is buried in

“I still wait for him to come back home, even though I saw his body. I still can’t believe it,” she says, tears running down her face.

“Sometimes I sit and think who my grandchildren could have been. It’s impossible to live like this. It’s not life.”

Russia doesn’t publish its casualty figures but the UK estimates that more than 750,000 Russian troops have either been killed or wounded in the three years since the Kremlin’s full-scale invasion began.

Valentin is buried in a cemetery on the outskirts of Rybinsk – a 20-minute bus ride for Elena. There are dozens and dozens of military graves there, each one marked with flags. The grave next to Valentin is for a serviceman killed on the same day as him.

It’s rare for anyone to speak openly in Russia about the war because criticising it can land you in prison. But Elena is determined to prevent other mothers from suffering the same experience.

“I want only one thing – for all children to come home,” she said.

“I want them to hear us and give us back our children in the same state we gave them, not cold.”

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Pope Francis ‘resting’ in hospital and night ‘went well’, says The Vatican

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Pope Francis 'resting' in hospital and night 'went well', says The Vatican

Pope Francis is in good spirits, eating normally and continuing to receive treatment, Vatican sources have said.

Earlier on Monday morning, the Vatican issued a short statement saying the pontiff was “resting” in hospital and the night “went well”.

The updates on his health follow a statement on Sunday in which the Vatican said Francis was in a critical condition and was showing an “initial, mild” kidney problem.

It said he was “vigilant and well-oriented”, and took part in mass in hospital with those caring for him, but due to the complexity of his case the prognosis was “reserved”.

The Pope, 88, has been at Rome’s Gemelli Hospital since 14 February and is being treated for double pneumonia and chronic bronchitis.

He has a history of respiratory illness, having lost part of one of his lungs to pleurisy as a young man. He also had an acute case of pneumonia in 2023.

Today marks Francis’s 11th day at Gemelli – the longest hospital stay of his papacy. He spent 10 days there in 2021 after he had 33cm (13ins) of his colon removed.

Father Nunzio Corrao, the chaplain at the hospital, said the time had come “to hope against hope” for the Pope, according to Italian media reports.

The Vatican said its secretary of state, Pietro Parolin, will lead a mass in St Peter’s Square this evening at 9pm local time (8pm UK time) to pray for him – and others in hospital.

Pic: AP
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A mass to pray for Pope Francis is being held in St Peter’s Square in Rome tonight. Pic: AP

It comes after the Vatican released a message from the Pope on Sunday – his first from his hospital bed – in which he asked people to pray for him.

His message said: “I am confidently continuing my hospitalisation at the Gemelli Hospital, carrying on with the necessary treatment; and rest is also part of the therapy!”

He added: “In recent days I have received many messages of affection, and I have been particularly struck by the letters and drawings from children.

“Thank you for this closeness, and for the prayers of comfort I have received from all over the world! I entrust you all to the intercession of Mary, and I ask you to pray for me.”

The message is understood to have been written in the last few days.

On Saturday, the Vatican said the pontiff was in a critical condition after a “prolonged respiratory crisis” that required a high flow of oxygen.

It said he had blood transfusions after tests revealed thrombocytopenia, which is associated with anaemia.

Doctors said on Friday he was “not out of danger” and was expected to remain in hospital for at least another week.

They warned the main threat he faced was sepsis, that can occur as a complication of pneumonia, and lead to organ failure and death.

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A view of the Agostino Gemelli Polyclinic, in Rome, Monday, Feb. 24, 2025 where the Pontiff is hospitalized since Friday, Feb. 14. (AP Photo/Alessandra Tarantino)
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Monday marks Pope Francis’s 10th day at Gemelli Hospital in Rome. Pic: AP

Millions around the world have been concerned about Francis’s increasingly frail health.

His condition has given rise to speculation over a possible resignation – which the Vatican has not commented on.

In New York on Sunday, Cardinal Timothy Dolan said the Catholic faithful were united “at the bedside of a dying father”.

“As our Holy Father Pope Francis is in very, very fragile health, and probably close to death,” he said in his homily from the pulpit of St Patrick’s Cathedral.

He later told reporters he hoped and prayed that Francis would “bounce back”.

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Diverted American Airlines flight escorted by Italian fighter jets after ‘bomb threat’

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Diverted American Airlines flight escorted by Italian fighter jets after 'bomb threat'

An American Airlines flight travelling from New York to New Delhi was diverted midair due to a “bomb threat”.

Flight 292 landed at Rome’s Leonardo da Vinci Rome Fiumicino Airport “due to a possible security issue,” the airline said in a statement on Sunday, adding later the threat “was determined to be non-credible”.

The airline did not clarify what the security issue was, but a source familiar with the situation told Sky News’ US partner network NBC News it was a bomb threat sent via email.

The Federal Aviation Administration said the crew reported the security issue.

“Safety and security are our top priorities, and we apologise to our customers for the inconvenience,” the airline said in a statement.

An American Airlines plane is seen from the cockpit of an Italian Air Force Eurofighter aircraft, as it is escorted, in this handout photo obtained by Reuters on February 23, 2025. Italian Air Force/Handout via REUTERS THIS IMAGE HAS BEEN SUPPLIED BY A THIRD PARTY
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The view from the cockpit of the fighter jet. Pic: Italian air force/Reuters

An Italian Air Force Eurofighter aircraft escorts an American Airlines plane in this handout photo obtained by Reuters on February 23, 2025. Italian Air Force/Handout via REUTERS THIS IMAGE HAS BEEN SUPPLIED BY A THIRD PARTY
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Pic: Italian air force/Reuters

The flight requested a diversion to Rome’s Leonardo da Vinci Rome Fiumicino Airport at around 2pm local time, Roberto Rao, a spokesperson for the airport.

“We immediately agreed and organised a safe landing,” Mr Rao told NBC News.

“We don’t know what the security concern was, but my opinion is that it was serious enough to divert the plane, but not urgent, because we received the alert when the plane was over the Caspian Sea, a three hours’ flight from Rome.”

Once in Italian airspace, the plane was escorted by two Italian air force fighter jets and landed in Rome at around 5.30pm local time.

American Airlines flight AA292 en route from New York to New Delhi that turned around over the Caspian Sea Sunday, Feb. 23, 2025, sits on the tamarack of Rome's Leonardo da Vinci International airport. (AP Photo/Kirsty Wigglesworth)
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The flight on the ground in Rome. Pic: AP

‘What’s going on here?’

Neeraj Chopra, one of the 199 passengers on board, said the captain announced the plane had to turn around about three hours before it was supposed to land in New Delhi because of a change in “security status”.

Mr Chopra, who was traveling to India to visit family, described the mood on board as calm until the captain later announced that fighter jets would be escorting their plane to Rome.

“I felt a little panic of, okay, what’s going on here?” Mr Chopra told the Associated Press. “There’s got to be like something bigger going on here.”

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Jonathan Bacon, 22, added that once on the ground, all passengers were loaded on to buses and taken to the terminal, where each passenger and their personal items underwent additional security screenings that were time-consuming and felt “slightly heightened”.

More than two hours after landing, Mr Bacon and his friend said they were still waiting for their checked baggage. “It was definitely the longest flight to Europe I’ve ever taken,” he said.

American Airlines said the plane was inspected and cleared to depart again for New Delhi “as soon as possible” on Monday, after the crew gets some rest.

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