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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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In a time of change Sky News spent a critical year on a farm – find out what we learnt

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In a time of change Sky News spent a critical year on a farm - find out what we learnt

Many months before farmers found themselves on the front pages of newspapers, after protesting in Whitehall against the new government’s inheritance tax rules, we at Sky News embarked upon a project.

Most of our reports are relatively short affairs, recorded and edited for the evening news. We capture snapshots of life in households, businesses and communities around the country. But this year we undertook to do something different: to spend a year covering the story of a family farm.

We had no inkling, at the time, that farming would become a front-page story. But even back in January, 2024 was shaping up to be a critical year for the sector. This, after all, was the year the new post-Brexit regime for farm payments would come into full force. Having depended on subsidies each year for simply farming a given acreage of land, farmers were now being asked to commit to different schemes focused less on food than on environmental goals.

This was also the first full year of the new trade deals with New Zealand and Australia. The upshot of these deals is that UK farmers are now competing with two of the world’s major food exporters, who can export more into Britain than they do currently.

You can watch the Sky News special report, The Last Straw, on Sky News at 9pm on Friday

Read more
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Rhetoric rises in farmer inheritance tax row – with neither side seemingly prepared to budge

On top of this, the winter that just passed was a particularly tough one, especially for arable farmers. Cold, wet and unpredictable – even more so than the usual British weather. It promised to be a challenging year for growing.

More on Farming

With all of this in mind, we set out to document what a year like this actually felt like for a farm – in this case Lower Drayton Farm in Staffordshire. In some respects, this mixed farm is quite typical for parts of the UK – they rear livestock and grow wheat, as well as subcontracting some of their fields to potato and carrot growers.

A look at farming reimagined

But in other respects, the two generations of the Bower family here, Ray and Richard, are doing something unusual. Seeing the precipitous falls in income from growing food in recent years, they are trying to reimagine what farming in the 21st century might look like. And in their case, that means building a play centre for children and what might be classified as “agritourism” activities alongside them.

The Bower family
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The Bower family

The upshot is that while much of their day-to-day work is still traditional farming, an increasing share of their income comes from non-food activity. It underlines a broader point: across the country, farmers are being asked to do unfamiliar things to make ends meet. Some, like the Bowers, are embracing that change; others are struggling to adapt. But with more wet years expected ahead and more changes due in government support, the coming years could be a continuing roller coaster for British farming.

With that in mind, I’d encourage you to watch our film of this year through the lens of this farm. It is, we hope, a fascinating, nuanced insight of life on the land.

You can watch the Sky News special report, The Last Straw, on Sky News at 9pm on Friday

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Ukraine War: Vladimir Putin open to peace talks in Slovakia

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Ukraine War: Vladimir Putin open to peace talks in Slovakia

Russian President Vladimir Putin has said he would be open to peace talks with Ukraine in Slovakia “if it comes to that”. 

Mr Putin said Slovakian Prime Minister Robert Fico, who this week visited the Kremlin, had offered his country as a location for negotiations as the war in Ukraine nears the three-year mark.

The Russian president said the Slovakian authorities “would be happy to provide their own country as a platform for negotiations”.

“We are not opposed, if it comes to that. Why not? Since Slovakia takes such a neutral position,” Mr Putin said, adding he was resolved to end the conflict in Ukraine, which started with a land, air and sea invasion of Russia’s smaller neighbour in February 2022.

Follow the latest updates on the war in Ukraine

Ukraine is yet to comment on Slovakia’s offer but President Volodymyr Zelenskyy has repeatedly criticised the country, which borders Ukraine, for the friendly tone Mr Fico has struck towards Russia since his return to power after an election in 2023.

Mr Fico has been critical of EU support for Ukraine, where millions have been displaced since Mr Putin’s decision to launch a “special military operation” to “denazify” and “demilitarise” the 37 million-strong country.

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Mr Zelenskyy on North Korea and Slovakian PM in Moscow

Mr Putin has repeatedly said Russia is open to talks to end the conflict with Kyiv, but that it would nevertheless achieve its goals in Ukraine.

He has previously demanded Ukraine withdraw its bid to join NATO and asked it to recognise Russia’s gains. Both Kyiv and the West have rejected those demands.

Read more from Sky News:
Boxing Day tsunami ‘impossible to forget’ – Watch
Farage willing to help Mandelson negotiate with Trump

But while Mr Zelenskyy had for most of the conflict insisted Ukraine would keep fighting until it regained control of its territories, his position on negotiations now appears to have shifted.

In an interview with Sky News, Mr Zelenskyy suggested a ceasefire deal could be struck if the Ukrainian territory he controls could be taken “under the NATO umbrella”.

This would then allow him to negotiate the return of the rest later “in a diplomatic way”.

The Ukrainian leader admitted last week his forces would be unable to recapture any territories occupied by Russia in the east of Ukraine and the Crimean peninsula.

While Kyiv would never recognise Russia’s rule, he said diplomacy is the only option to get Mr Putin to withdraw his army.

The war in Ukraine has taken a devastating toll on Russia too. UK government and military analysis estimates that Russia has lost around half a million troops killed or wounded in Ukraine.

Such is the pressure on manpower that The Kremlin turned to one of its remaining allies, North Korea, to provide additional forces.

It’s thought 10,000 to 12,000 troops were sent in October to fight alongside the Russian military in the fighting in the Kursk region.

However it’s suggested their lack of combat experience has resulted in heavy losses, with Mr Zelenskyy saying earlier this week that 3,000 North Korean troops have already been killed and wounded.

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Special educational needs children ‘segregated and left to struggle in wrong schools to save money’

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Special educational needs children 'segregated and left to struggle in wrong schools to save money'

Children with special educational needs are being “segregated” and left to struggle in the wrong schools because councils are trying to “save on costs”, parents have told Sky News. 

Maire Leigh Wilson, whose four-year-old son has Down’s syndrome, says she “shudders to think” where he would be now had she not been in a “constant battle” with her council.

“I think he would probably just be at the back of a classroom, running around with no support and no ability to sign or communicate,” she said.

Mrs Leigh Wilson wanted her son Aidan to go to a mainstream school with additional specialist support, but her council, who decide what is known as a child’s Education Health and Care Plan (EHCP), wanted him to attend a special school.

The number of EHCPs being appealed by parents has risen “massively”, according to education barrister Alice De Coverley.

She said councils are struggling to meet the volume of demand with “stretched budgets”, and parents are also more aware of their ability to appeal.

Mrs De Coverley said more than 90% of tribunals are won by parents, in part because councils do not have the resources to fight their cases.

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She said, in her experience, parents of children with special educational needs will put “anything on the line, their homes, their jobs”.

On whether she thinks the system is rigged against parents, Mrs De Coverley said: “I’m not sure it’s meant to be. But I think that parents are certainly finding it very tough.”

She added the number of “unlawful decisions” being made by local authorities means parents who can afford it are being “utterly burnt out” by legal challenges.

Read more:
Three in four parents of SEND children forced to give up work or cut hours

Maire Leigh Wilson with her son, Aiden, four
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Maire Leigh Wilson with her son, Aiden, four

Mrs Leigh Wilson’s case was resolved before making it to court.

Her council, Hounslow in southwest London, said they complete more than four in five new EHCPs within the statutory 20-week timescale, twice the national average.

Hounslow Council said they “put families at the heart of decision-making” and young people in the area with special educational needs and disabilities achieve, on average, above their peers nationally.

They admitted there are areas of their offer “that need to be further improved” and they are “working closely with families as a partnership”.

“We have a clear and credible plan to achieve this, and we can see over the last 18 months where we have focused our improvement work, the real benefits of an improved experience for children, young people, and their families,” a Hounslow Council spokesman said.

He added the council had seen the number of EHCPs double in the last decade and they “share parents’ frustrations amid rising levels of national demand, and what’s widely acknowledged as a broken SEND system”.

Emma Dunville wanted her son, Albie, to go to a special school but the council took too long to assess him
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Emma Dunville wanted her son, Albie, to go to a special school but the council took too long to assess him

Emma Dunville, a friend of Mrs Leigh Wilson whose son also has Down’s syndrome, describes her experience trying to get the right education provision for her child as “exhausting mentally and physically”.

She said: “For the rest of his life we’ll be battling, battling, battling, everything is stacked up against you.”

Unlike Mrs Leigh Wilson, Mrs Dunville wanted her son Albie to go to a special school, but she had to wait more than a year for an assessment with an education psychologist to contribute to the council’s decision, which meant she missed the deadline for an EHCP.

“The people making these decisions just don’t see that all children with Down’s syndrome are totally different and can’t be seen as the same.”

The guidelines are that if there are not enough local authority-employed education psychologists they should seek a private assessment, but her local authority did not do that.

Mrs Dunville said her son has been “segregated” in a mainstream school, where they are “trying their best” but “it’s just not the right setting”.

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