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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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What if Romeo had a scar? Or Juliet a facial difference? The actors challenging screen conventions

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What if Romeo had a scar? Or Juliet a facial difference? The actors challenging screen conventions

Crystal was 18 when bone cancer changed her face. On top of chemotherapy and operations, she had to deal with other painful realities too.

She told Sky News: “Pre-cancer, and everything that happened I wasn’t aware how people who had facial differences were villainised or victimised.

Crystal before her diagnosis
Image:
Crystal before her diagnosis

“Experiencing that, seeing the trauma, I’ve been so affected by people staring at me in the street, and hate comments about my appearance.”

She believes part of the problem is the screen portrayal of visibly different characters: “There’s a narrative in Hollywood, especially that’s been going on for years, that people are not addressing and seeing that these are real people.”

Refusing to let her differences keep her from pursuing her dreams, Crystal studied acting at LAMDA, one of the UK’s top drama schools.

Now a professional actress, she knows her appearance will always be judged.

“[My visible difference] is on my face. I can’t really hide anything. Every time I talk or enter a room, it’s not like anyone’s fault, I just know that people have that first perception or viewpoint of me.”

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With aspirations to one day appear in a Marvel movie, she hopes her drive to perform will help others in the future.

“I didn’t have anyone who looked like me as a role model… It would have just been so much better if I’d had that one person to look up to, to be inspired by.”

Crystal graduated from LAMDA in 2024
Image:
Crystal graduated from LAMDA in 2024

Lack of representation is not the only problem. When visible difference does make it onto the screen, misrepresentations and negative overtones often reinforce stigma.

Nearly one in five people in the UK self-identifying as having a visible difference, such as a mark, scar or condition, according to charity Changing Faces.

New research they conducted into the way disfigurement is portrayed on screen found that people with visible differences were over twice as likely to be shown as a victim or a villain than as a love interest.

Film and television have used scars, burns and birthmarks as a shorthand for villainy across the genres for years. From Bond to Batman and Star Wars, to more family-friendly productions such as The Lion King.

Heath Ledger as the infamous Joker. Pic: Rex Features
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Heath Ledger as the infamous Joker. Pic: Rex Features

Rami Malek as Safin in No Time To Die, complete with scars. Pic: Universal
Image:
Rami Malek as Safin in No Time To Die, complete with scars. Pic: Universal

And while visibly different characters aren’t common on screen, a woman with a physical difference in film or TV is even rarer.

Author and entertainment journalist Kristen Lopez says it’s because women’s value on screen is so tied up with their sexuality.

The author of Popcorn Disabilities: The Highs and Lows of Disabled Representation in the Movies has even come up with a term to describe the industry’s attempt to keep their leading ladies “sexy and beautiful”.

“You often see what I call ‘pretty disabilities’. It’s a disability that is not going to affect the physical perfection of the actress. And it will also allow for an A-list, usually non-disabled actress, to continue to play the character.”

Lopez says for that reason, films are more comfortable with portraying blind or visually impaired women, deaf women, or non-verbal women, because their disability “doesn’t mar the face”.

Speaking from her own experience of growing up with brittle bone disease, she says: “I worry about the next generation of disabled girls – what are they seeing? Do they feel represented?

“How do you navigate adolescence if you don’t see anybody that looks like you doing the things that every other young person is doing?”

Romeo Olukotun was just one year old when an accident left him with second and third-degree burns on his torso, chest and neck.

With his accident not spoken about at home, he admits, “I just kind of had to deal with that on my own”.

He did find some flashes of inspiration, including from singer Seal.

Romeo was just one when an accident left him with burns on his chest, neck and stomach
Image:
Romeo was just one when an accident left him with burns on his chest, neck and stomach

“I loved how even though he had a visible difference and scarring on his face, he wasn’t looked down because of that. He was seen for his talent.”

With his confidence taking a hit due to his scars while at secondary school and university, he rebuilt his self-esteem as an adult through cheerleading.

Later spotted at a music video shoot he’d gone along to with a friend, he’s now an actor and model. But his visible differences have, at times, affected his casting.

Pic: Changing Faces
Image:
Pic: Changing Faces

Romeo told Sky News: “Because my scar on my neck looks like I’ve been stabbed, I would often be asked to ‘Try this [performance] like a thug or someone who’s on the streets’. And I didn’t like being labelled as that. I’m someone who is much more than my scars.”

He’s now a man on a mission: “I want to be someone who shows other people with a visible difference that they can be anything. They can play the romantic lead, they can play a villain if they want to. They can be a hero, not just be labelled as someone sinister and evil, Machiavellian.”

Pic: Changing Faces
Image:
Pic: Changing Faces

While the film and TV industries might be slow to change, LAMDA vice principal Dr Philippa Strandberg-Long is hopeful for the future.

“We have to make our students aware of the industry that they are going into and not, I guess, create a utopia where they’re not aware of the industry they’re going into. However, we can change it from how we educate our students that come out.

“Things won’t change overnight, but it will change over time. So, we have to put in the work at the grassroots, which is here.”

Changing Faces is the UK’s leading charity for anyone with a visible difference. They have a confidential support and information line for anyone dealing with the impact of visible difference.

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Ibiza lizards ‘near extinction’ due to invasive snakes and mounting litter

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Ibiza lizards 'near extinction' due to invasive snakes and mounting litter

Conservationists in Ibiza are warning the island’s native bright blue and green lizards are coming ever closer to extinction due to the mounting threats of invasive snakes and tourists’ litter.

The Ibiza wall lizard is endemic to Ibiza and neighbouring Formentera and is vital to the ecosystem of the islands, experts say, for pollinating plants and controlling pests.

Since the 2000s, the small, colourful reptiles, which are harmless to humans, have become endangered due to the proliferation of invasive snakes that first arrived in imported trees.

Conservationists say Ibiza lizards are endangered. Pic: Dean Gallagher
Image:
Conservationists say Ibiza lizards are endangered. Pic: Dean Gallagher

Conservation foundation IbizaPreservation says snakes are now present on up to 90% of the island, while the lizard population has decreased massively, believed to have disappeared from about 70%.

But there is also another issue affecting the species – litter left mainly by tourists at beauty spots.

Dean Gallagher, a snake catcher on the island, says he is constantly finding the bodies of dead lizards stuck inside discarded bottles and cans at Es Savinar, a southerly viewpoint where people often gather for sunset.

“I’m finding these lizards trapped in cans and bottles,” he tells Sky News. “Once they get inside their feet get wet from the drink inside, the beer or the Red Bull, and they can’t get out. Sun comes up, heats up the bottle, the can, and just fries a lizard inside. It’s absolutely devastating.”

Dean Gallagher has lived in Ibiza for more than 20 years
Image:
Dean Gallagher has lived in Ibiza for more than 20 years

Tourism accounts for about 84% of Ibiza’s economy and is vital for the island, with tourist spending reaching 4.3bn euros in 2024, according to the Balearic Institute of Statistics (IBESTAT) – an increase of 62% since 2016. The number of tourists reached a record high of more than 3.7m for Ibiza and neighbouring Formentera in 2023 – an increase of almost 25% since 2016.

The land Dean looks after at Es Savinar is private, he says, but people ignore signs and fences which were replaced at the beginning of the summer.

“We do rubbish collections probably once or twice a week,” he says. “We clear the whole area of bottles and cans then the next time, we go back and there’s even more.

“Bottles can cause bush fires. The forests are really dry at the moment, just one spark can set this place alight. And [litter] is also killing our lizards. They’re marvellous, beautiful creatures, they’re not aggressive and they keep the bugs away. The ecological value is really important.”

Signs have been put up around the private land. Pic: Dean Gallagher
Image:
Signs have been put up around the private land. Pic: Dean Gallagher

Dean lives near Santa Eulalia, where he says numbers are scarce. “Lots of parts of the north of the island now, they’ve completely diminished and it’s very sad,” he adds.

“And the very southwest corner of the island where this viewpoint is, this is the last place where they are in stable numbers. But the excessive rubbish, tourism, snakes, are gonna wipe them out completely.”

Gallagher says he is constantly finding the reptiles trapped in glass bottles and cans
Image:
Gallagher says he is constantly finding the reptiles trapped in glass bottles and cans

Visual surveys of areas of Ses Salines Natural Park by environmental association GEN-GOB have found the population there has decreased by between 70% and 90% since 2023.

GEN-GOB, Friends Of The Earth Ibiza and IbizaPreservation are among several organisations that have been working to save the species in recent years.

Read more:
Is Ibiza at breaking point?

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Ibiza’s shanty towns – the side of the island most do not see

Jordi Serapio, coordinator of Protegim Ses Sargantanes, IbizaPreservation’s lizard protection project, says abandoned bottles and cans are “deadly traps” for the animals.

And snake numbers continue to grow and expand toward territories where lizards still remain, he adds. The most common snake on the island – and the biggest danger to lizards – is the horseshoe whip snake, but other types have been spotted.

“It has followed a northeast to southwest expansion,” he says. “The highest snake densities are observed in what they have called the ‘invasion front’ – this is known precisely thanks to trapping.

“In contrast, in areas where lizards have already become extinct, there appears to be a much lower density of snakes.”

So the more food available for the snakes, the higher the numbers.

“This is something common in most biological invasions, which end up regulating themselves naturally,” Jordi says. “The unknown in this case is whether some lizard populations will manage to survive and adapt. Although everything seems to indicate that they won’t.”

He also highlights another problem – predation by both feral and domestic cats – which he says is a growing threat.

“In the current context of the species’ extinction, any additional pressure worsens the situation.”

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O’s 1 out from being no-hit, score 4 to stun L.A.

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O's 1 out from being no-hit, score 4 to stun L.A.

BALTIMORE — Jackson Holliday homered with two outs in the bottom of the ninth inning to deny Yoshinobu Yamamoto a no-hitter, and the Baltimore Orioles weren’t satisfied with that, rallying for four runs in the inning to defeat the Los Angeles Dodgers 4-3 in a delirious comeback Saturday night.

Emmanuel Rivera won it with a two-run single off Tanner Scott, who also allowed a walk-off homer to Orioles rookie Samuel Basallo the previous night. But the Orioles did the bulk of their damage against Blake Treinen (1-3), who relieved Yamamoto after Holliday’s homer. He gave up a double to Jeremiah Jackson, hit Gunnar Henderson and walked Ryan Mountcastle and Colton Cowser to make it 3-2.

Scott came on with the bases loaded, and Rivera lined a single to center.

According to Elias, the Dodgers are just the second team in the Expansion Era (since 1961) to lose a game in nine innings after carrying a no-hitter through 8⅔ innings. On July 9, 2011, the Dodgers broke up the Padres’ combined no-hitter to win 1-0.

Los Angeles had a win probability of 99.6% with two outs before Holliday’s ninth-inning homer, according to ESPN Analytics.

Yamamoto came within one out of the major leagues’ first no-hitter of 2025. He allowed only two baserunners, both on third-inning walks, before Holliday’s drive. The 27-year-old right-hander tied a career high with 10 strikeouts. He threw 112 pitches, also a career high since coming to the U.S.

Yamamoto was removed after that and received a standing ovation by fans of both teams.

Camden Yards has hosted only one no-hitter since opening in 1992, and it was by another Japanese star. Hideo Nomo threw one on April 4, 2001, for the Boston Red Sox against the Orioles.

Shohei Ohtani hit an RBI grounder in the third. Mookie Betts added a run-scoring single in the fifth and an RBI triple in the seventh.

The Dodgers have not thrown a no-hitter since May 4, 2018, when Walker Buehler, Tony Cingrani, Yimi Garcia and Adam Liberatore pitched a combined effort against the San Diego Padres in Mexico. The last solo no-hitter by the team was Clayton Kershaw’s on June 18, 2014, against Colorado.

The last time the Orioles were no-hit was by Japanese right-hander Hisashi Iwakuma of the Seattle Mariners on Aug. 12, 2015.

The Associated Press contributed to this report.

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