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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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Sources: Dodgers’ Betts out due to fractured toe

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Sources: Dodgers' Betts out due to fractured toe

LOS ANGELES — Mookie Betts stubbed a toe in his left foot during an off-the-field incident and missed the opener of the Los Angeles Dodgers‘ highly anticipated series against the New York Yankees on Friday.

Betts is not expected to go on the injured list, according to Dodgers manager Dave Roberts, but he will not start against the Yankees on Saturday or Sunday. Roberts said the hope is that Betts will return to the lineup shortly thereafter.

“For me, right now, it’s just day-to-day,” Roberts said after the Dodgers’ 8-5, come-from-behind win.

The incident, which affected the tip of Betts’ second toe, was believed to have occurred late Wednesday night, after the Dodgers returned from a six-game road trip, when Betts banged his toe against a piece of furniture at his house. Betts called Roberts to inform him about his toe on Friday morning, then underwent X-rays at Dodger Stadium later that afternoon.

Those X-rays revealed a fracture, a source told ESPN, confirming what Betts told the Los Angeles Times after Friday’s game. The Dodgers’ training staff will spend the weekend attempting to get the swelling down on his toe. At this point, the Dodgers don’t believe he can make the injury any worse by playing on it.

Said Roberts: “It’s going to be one of those situations per his [pain] tolerance.”

Betts’ injury isn’t the Dodgers’ most serious at the moment. Late-inning reliever Evan Phillips, who was rehabbing a forearm injury, didn’t feel right playing catch earlier this week and will undergo Tommy John surgery next week, knocking him out for all of 2025 and most of 2026.

Phillips, 30, was released by the Baltimore Orioles in August 2021 and designated for assignment by the Tampa Bay Rays less than two weeks later. The Dodgers picked him up and turned him into a valuable late-game option. From 2022 to 2024, Phillips posted a 2.21 ERA and 0.92 WHIP, saved 44 games and struck out 206 batters in 179 regular-season innings.

But Phillips dealt with arm issues during last year’s postseason run and was left off the team’s World Series roster. He then went on the IL because of a rotator cuff strain in the middle of March, returned a month later, notched seven scoreless appearances, then went back on the IL on May 7 because of what the team called forearm discomfort. Platelet-rich-plasma injections did not take. Phillips never got better.

“As we started getting into it, it wasn’t really responding,” Dodgers general manager Brandon Gomes said. “We felt like this could be a possibility, so as he got deeper into the process and it wasn’t really getting better, the decision to do it was pretty much evident with our information.” The loss of Phillips is coupled with the Dodgers having four other high-leverage relievers on the IL — Brusdar Graterol, Blake Treinen, Kirby Yates and Michael Kopech, all of whom are right-handed.

The Dodgers tried to backfill some of that depth by trading for former All-Star closer Alexis Diaz on Thursday. But Diaz, who struggled so badly this season that the Cincinnati Reds optioned him to Triple-A, will initially work out of the Dodgers’ spring training complex in Glendale, Arizona.

The Dodgers also have three starting pitchers — Blake Snell, Tyler Glasnow and Roki Sasaki — recovering from shoulder injuries, with Shohei Ohtani not expected to join the rotation until sometime after the All-Star break.

The lineup, at least, had been healthy. Until now.

Betts, 32, got off to a slow start but was still slashing .254/.338/.405 with eight home runs and five stolen bases while slotting between the hot-hitting Ohtani and Freddie Freeman in the No. 2 spot. More notably, Betts had proved to be a capable major league shortstop after working during the offseason at the position.

The hope is that the toe injury doesn’t set him back much longer than the rest of this weekend.

In the meantime, Miguel Rojas will continue to get starts at shortstop.

“It’s a good part about having depth,” Gomes said. “Keep the train moving.”

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Trout returns in new spot, has hit in Angels’ win

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Trout returns in new spot, has hit in Angels' win

CLEVELAND — Mike Trout originally expected to return to the Los Angeles Angels‘ lineup Monday in Boston.

But the timeline was moved up one series and three days.

Trout was activated off the injured list and went 1-for-5 as the designated hitter in Friday night’s 4-1 win over the Cleveland Guardians. The Angels slugger missed 26 games because of soreness in his left knee that was eventually diagnosed as a bone bruise. The three-time American League MVP had two operations last year on the knee after tearing his meniscus.

“Felt good. Struck out on two at-bats, but other than that, felt all right,” said Trout, who batted fifth for the first time in 1,532 starts.

Trout lined a base hit to left-center in the fourth inning. He thought he had a hit in his first at-bat in the second inning, but Cleveland third baseman José Ramírez made a nice grab on a low line drive.

“I thought he had some good at-bats, considering that he hadn’t seen live pitching in a while,” Angels manager Ron Washington said. “He hit the ball hard three times today. They made some good pitches when he struck out. But welcome back, Mike.”

Trout’s return also helped the Angels snap a five-game losing streak and improve to 28-30.

It was the first time since Sept. 26, 2011, Trout’s rookie season, that he started a game hitting lower than third.

Washington is happy to have Trout back, especially because he noted Trout wasn’t aggressive in rushing in his return. Washington also knows that Trout isn’t ready to return to his normal spot batting second or third.

“He hasn’t seen anything. So when you look at what we have, that’s where he sits,” Washington said before the game. “It doesn’t make sense for him to protect [Logan] O’Hoppe. So, I’ll put Mike behind him to protect O’Hoppe. He’s not ready to be at the top of the lineup, especially with those guys up there. As we go along the next couple of days, he’s not going to remain fifth.”

The 33-year-old Trout is hitting .180 with 9 home runs, 18 RBIs and a .712 OPS in 30 games. He will be the designated hitter for the weekend series against the Guardians before possibly returning to right field when the Halos head to Boston on Monday for a three-game series.

Even though Trout has shied away from wanting to be the designated hitter, he has done well in that spot. In eight games this season, he is 9-for-33 (.273) with 6 home runs and 9 RBIs.

Trout said whether he plays more games than originally planned at DH the remainder of the season is something that remains to be seen.

“Bone bruises are tricky. I know I am going to be sore, but I can deal with it,” he said. “I definitely have to be cautious, especially the first couple games.”

Trout has missed 404 of the Angels’ 665 games — almost 60% — since May 17, 2021, when he tore his calf muscle against Cleveland and was sidelined for the rest of that season. This is the fifth straight year he has had a stint of at least 25 games on the IL.

He missed five weeks of the 2022 season because of a back injury, and all but one game after July 3, 2023, after he broke a bone in his hand on a foul ball. Trout played in 29 games last season before the meniscus injury.

“There’s so many games that any sense of newness or something to make you excited is something that you’d latch on to. So, today is definitely a moment like that,” O’Hoppe said about Trout’s return. “He’s the heart of this organization. So, we’re happy to have our heart beating again for sure.”

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Ministers to kick off hunt for successor to Ofcom chair Lord Grade

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Ministers to kick off hunt for successor to Ofcom chair Lord Grade

Ministers are to kick off the hunt for a new chair of the communications regulator as Lord Grade of Yarmouth prepares to bow out after a single term at the helm.

Sky News has learnt that the Department for Science, Innovation and Technology (DSIT) – which now leads oversight of Ofcom in Whitehall – is drawing up proposals to launch a recruitment process in the coming months.

Lord Grade, the veteran broadcast executive who held senior posts at the BBC, ITV and Channel 4, has served as Ofcom chair since May 2022.

His four-year term is not due to end for another 11 months, and there was no suggestion this weekend that he would leave the role ahead of that point.

Insiders said, however, that there was little prospect of him seeking to be reappointed for a second term in the job.

The now non-affiliated peer’s appointment to the post in 2022 came after a controversial recruitment process and was signed off by Nadine Dorries, the then Tory culture secretary.

Responsibility for Ofcom board appointments has switched since then from the Department for Culture, Media and Sport.

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Peter Kyle, the science secretary, authorised the recruitment of Tamara Ingram, an advertising industry stalwart, as Ofcom’s deputy chair, last November.

The search for a new Ofcom chair will come after a significant extension of its remit to encompass areas such as online harms.

Both DCMS, which has responsibility for the media industry, and the Department for Business and Trade also have substantial engagement with Ofcom.

As well as a role in appointing directors to the board of state-owned Channel 4, which is hunting both a chair and chief executive, Ofcom regulates companies such as Royal Mail, as well as the BBC.

This week, the watchdog said it was pursuing action against the formerly publicly owned postal services company over its failure to hit statutory delivery targets.

Ofcom also regulates the UK telecoms industry, making it one of the largest economic regulators in Britain.

Mr Kyle said this week that Ofcom should also prepare to be given regulatory oversight of the fast-growing data centre industry.

One of the tasks of Lord Grade’s successor is likely to be long-term executive leadership succession planning.

Dame Melanie Dawes, Ofcom’s chief executive, has held the role since 2020, although there is no indication that she intends to step down in the short term.

It was unclear this weekend whether any of Ofcom’s existing board members might seek to take over from Lord Grade.

Its slate of non-executive directors includes recently appointed Lord Allan of Hallam, a former MP, and Ben Verwaayen, the former BT Group chief executive.

Mr Verwaayen is due to step down from the Ofcom board at the end of the year.

The hunt for Ofcom’s next chair will come amid a push led by Sir Keir Starmer and Rachel Reeves to shake up Britain’s economic regulators as they seek ways to remove red tape from the private sector.

DSIT has been contacted for comment, while Ofcom declined to comment.

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