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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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Politics

New English language and UK citizenship requirements for migrants as part of government crackdown

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New English language and UK citizenship requirements for migrants as part of government crackdown

Migrants will have to live in the UK for a decade before they can apply for citizenship under plans to reduce reliance on foreign workers. 

The change from five to 10 years will come with exceptions for people who make a “high contribution” to the economy or society, who will able to be fast-tracked for permanent settlement rights.

It comes on top of new English language requirements across every visa route, which will extend to adult dependents for the first time.

The measures will be announced by Sir Keir Starmer today ahead of the Immigration White Paper, which will set out further reforms to bring net migration down.

At a press conference later, the prime minister will say: “This is a clean break from the past and will ensure settlement in this country is a privilege that must be earned, not a right.

“And when people come to our country, they should also commit to integration and to learning our language.

“Lower net migration, higher skills and backing British workers – that is what this White Paper will deliver.”

Net migration – the difference between the number of people immigrating and emigrating to a country – soared when the UK left the EU in January 2020.

It reached 903,000 in the year to June 2023 before falling to 728,000 in mid-2024. But that is still well above its pre-Brexit high of 329,000 in the year up to June 2015.

The government is under pressure to tackle legal migration, as well as illegal immigration, amid Reform UK’s surge in the polls.

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Reform: Immigration ‘should be frozen’

However, experts have questioned whether some of the changes announced by Sir Keir today will have much of an impact, at least in the short term.

Currently, migrants have to live in the UK for five years to get indefinite leave to remain, or “settled status” if they are from the EU. They can then use this to apply for British citizenship, usually 12 months after settlement.

There were 162,000 grants of settlement in 2024, up 35% from 2023, and 270,000 grants of citizenship in 2024, up nearly a third on the previous year.

‘Contributions-based’ citizenship model

The new “contributions-based model” means people must spend a decade in the UK before applying to stay, unless they can show a “real and lasting contribution to the economy and society”.

Sir Keir Starmer at a summit in Oslo. Pic: PA
Image:
Sir Keir Starmer at a summit in Oslo. Pic: PA

The Home Office said this will include “high-skilled” and “high-contributing” individuals like nurses, doctors, engineers and AI leaders.

The details are still being fleshed out and will be put to consultation later this year rather than in the white paper, Sky News understands.

However, the thinking is that those who pay higher taxes or who work in a priority sector will be eligible to be fast-tracked. Home Secretary Yvette Cooper is also keen for discounts to apply to those who make an “outstanding contribution” to society, such as community leaders, it is understood.

English language requirements

The government also plans to raise English language requirements across every immigration route, so foreign workers speak a higher standard of English.

For the first time, this will also extend to all adult dependents by requiring them to demonstrate a basic understanding of English, which the government says will help people integrate and find employment.

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Dr Madeleine Sumption, director of the Migration Observatory at the University of Oxford, told Sky News that extending the amount of time people need to be in the UK to get permanent settlement rights is unlikely to significantly affect migration levels, as there is “no evidence” this affects their decision about whether to migrate.

Any impact would be seen in five to ten years, “when people get to that point of the visa journey”, she said, adding that the main effect of this policy would be to “bring in more visa-fee revenue to the Home Office” and “to make it harder for migrants to settle in”.

She said that language requirements “are more likely to have an impact on the number of visas granted”, as more than half of skilled worker visas over the past couple of years have gone to dependents.

“However, there’s no data on how many of them would have passed a language test so it is hard to say how big,” Dr Sumption added.

The Home Office has not put a figure on what sort of reduction these policies could achieve, with Ms Cooper to give more details in parliament on Monday afternoon.

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Minister reveals new immigration plans

On Sunday, she told Sky News’s Trevor Phillips that plans to close the care worker visa route and change the skilled visa threshold to require a graduate qualification would cut the number of overseas workers by about 50,000 this year.

Read More:
Labour’s shift on migration may assuage voters’ concerns – but risks impacting struggling care sector
Care workers plead for higher salaries amid recruitment crisis

However, she refused to put a target on the overall levels of net migration the government is aiming for, saying that approach “failed” under the Conservatives.

The Tories have admitted making mistakes in office, but are still calling for a binding immigration cap and want to repeal the Human Rights Act for immigration issues.

Shadow Home Secretary Chris Philp said Labour has “overseen the worst ever start to a year for illegal immigrants crossing the channel” adding: “The idea that Starmer is tough on immigration is a joke.”

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US

Ukraine, Gaza and China: Why Trump’s Middle East tour takes on new importance

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Ukraine, Gaza and China: Why Trump's Middle East tour takes on new importance

Donald Trump’s tour of the Middle East this week has taken on a new importance after a series of surprising developments on the wars in Ukraine and Gaza, and on trade between the US and China.

After a diplomatic flurry over the weekend, it seemed like steps were being taken towards some form of possible peace in both Gaza and Ukraine.

Alongside that, Washington claimed it had made “substantial progress” in trade talks with China, with treasury secretary Scott Bessent going as far as to say a deal had been agreed to cut the US trade deficit. But there was no mention of reducing tariffs.

Scott Bessent and Jamieson Greer speak to the media after trade talks with Chian in Geneva, Switzerland.
Pic: Reuters
Image:
Scott Bessent and Jamieson Greer speak to the media after trade talks with China in Geneva, Switzerland. Pic: Reuters

Mr Trump is due to travel to the Middle East later today on the first major foreign trip of his second presidency, visiting Saudi Arabia and then Qatar and the UAE.

It will coincide with a possible meeting between Ukraine’s Volodymyr Zelenskyy and Russia’s Vladimir Putin, in person in Turkey, and comes after Hamas said it would release a hostage, an Israeli soldier who holds American citizenship.

This leaves Mr Trump facing challenges on three fronts as he visits some of the richest nations in the world.

Zelenskyy and Putin to meet?

More on China

The US president previously claimed he could end the war in Ukraine in one day – something he has not done.

On Sunday, he put pressure on Mr Zelenskyy to sit down and meet with Mr Putin in person after Moscow put forward the proposal for talks in Istanbul.

This was something the leader from Kyiv quickly agreed to and it came after European leaders threatened Mr Putin with fresh sanctions.

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Putin’s call for peace talks genuine?

Thursday could see a potential first in-person meeting between the two leaders since Moscow’s invasion began.

It could mark an extraordinary moment in the ongoing war in Ukraine, however, the countries are seemingly still a long way from actual peace.

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A trade deal or a first step?

After Mr Trump declared war on the existing global trade system in April, hitting allies and foes alike with tariffs, it left many reeling and triggered an escalation with China, which slapped Washington with reciprocal measures.

While those are still in place, the US said on Sunday that the two have agreed a deal to cut the US trade deficit.

However, despite confidence from the US side, China’s vice premier He Lifeng described the meeting as an “important first step” that created a foundation only.

No mention was made of reducing tariffs and this would do little good elsewhere where tariffs continue to add friction to previously freer global trade.

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Israeli soldier to be released

In Gaza, previous efforts to achieve a ceasefire collapsed and Israel implemented a total ban on aid going into the enclave to try to pressure Hamas back to the negotiating table.

With charities warning that the 2.3 million Palestinians in Gaza face a humanitarian crisis, the militant group has said it will release Edan Alexander, an Israeli soldier who holds US citizenship.

It comes after Israel announced it intends to occupy the entire enclave, threatening years of more war.

FILE - Yael Alexander holds a poster of her son, Edan, who was taken hostage by Hamas militants on Oct. 7, 2023, during a weekly rally for families of hostages held in the Gaza Strip and their supporters, in Tel Aviv, Israel, Feb. 22, 2025. (AP Photo/Maya Alleruzzo, File)
Image:
Yael Alexander holds a poster of her son, Edan, who was taken hostage by Hamas militants.
Pic: AP

No exact date was given, but Hamas said it would release the 21-year-old as part of ongoing efforts to achieve a permanent ceasefire with Israel.

His expected release has been described as a “gesture of goodwill” by Steve Witkoff, Mr Trump’s special envoy to the Middle East.

The previously agreed ceasefire failed over disagreement on the transition from phase one onwards.

While Hamas wanted to progress to phase two, where work would be done towards Israel’s permanent withdrawal from Gaza and peace, Israel wanted to extend phase one and release more hostages.

Read more:
A week that could define Trump
Zelenskyy offers to meet Putin
Hamas says it will release hostage

Israel agreed to a framework proposed by the US that would see Hamas release half of the remaining hostages, its main bargaining chip, in exchange for a ceasefire extension and a promise to negotiate a lasting truce.

While Mr Alexander is only one hostage, it will be seen as a promising sign that Hamas returned to the negotiating table and Mr Trump will be in Qatar, the key mediator in so-far unsuccessful peace efforts.

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UK

New English language and UK citizenship requirements for migrants as part of government crackdown

Published

on

By

New English language and UK citizenship requirements for migrants as part of government crackdown

Migrants will have to live in the UK for a decade before they can apply for citizenship under plans to reduce reliance on foreign workers. 

The change from five to 10 years will come with exceptions for people who make a “high contribution” to the economy or society, who will able to be fast-tracked for permanent settlement rights.

It comes on top of new English language requirements across every visa route, which will extend to adult dependents for the first time.

The measures will be announced by Sir Keir Starmer today ahead of the Immigration White Paper, which will set out further reforms to bring net migration down.

At a press conference later, the prime minister will say: “This is a clean break from the past and will ensure settlement in this country is a privilege that must be earned, not a right.

“And when people come to our country, they should also commit to integration and to learning our language.

“Lower net migration, higher skills and backing British workers – that is what this White Paper will deliver.”

Net migration – the difference between the number of people immigrating and emigrating to a country – soared when the UK left the EU in January 2020.

It reached 903,000 in the year to June 2023 before falling to 728,000 in mid-2024. But that is still well above its pre-Brexit high of 329,000 in the year up to June 2015.

The government is under pressure to tackle legal migration, as well as illegal immigration, amid Reform UK’s surge in the polls.

Please use Chrome browser for a more accessible video player

Reform: Immigration ‘should be frozen’

However, experts have questioned whether some of the changes announced by Sir Keir today will have much of an impact, at least in the short term.

Currently, migrants have to live in the UK for five years to get indefinite leave to remain, or “settled status” if they are from the EU. They can then use this to apply for British citizenship, usually 12 months after settlement.

There were 162,000 grants of settlement in 2024, up 35% from 2023, and 270,000 grants of citizenship in 2024, up nearly a third on the previous year.

‘Contributions-based’ citizenship model

The new “contributions-based model” means people must spend a decade in the UK before applying to stay, unless they can show a “real and lasting contribution to the economy and society”.

Sir Keir Starmer at a summit in Oslo. Pic: PA
Image:
Sir Keir Starmer at a summit in Oslo. Pic: PA

The Home Office said this will include “high-skilled” and “high-contributing” individuals like nurses, doctors, engineers and AI leaders.

The details are still being fleshed out and will be put to consultation later this year rather than in the white paper, Sky News understands.

However, the thinking is that those who pay higher taxes or who work in a priority sector will be eligible to be fast-tracked. Home Secretary Yvette Cooper is also keen for discounts to apply to those who make an “outstanding contribution” to society, such as community leaders, it is understood.

English language requirements

The government also plans to raise English language requirements across every immigration route, so foreign workers speak a higher standard of English.

For the first time, this will also extend to all adult dependents by requiring them to demonstrate a basic understanding of English, which the government says will help people integrate and find employment.

👉 Listen to Electoral Dysfunction where you get your podcasts 👈

Dr Madeleine Sumption, director of the Migration Observatory at the University of Oxford, told Sky News that extending the amount of time people need to be in the UK to get permanent settlement rights is unlikely to significantly affect migration levels, as there is “no evidence” this affects their decision about whether to migrate.

Any impact would be seen in five to ten years, “when people get to that point of the visa journey”, she said, adding that the main effect of this policy would be to “bring in more visa-fee revenue to the Home Office” and “to make it harder for migrants to settle in”.

She said that language requirements “are more likely to have an impact on the number of visas granted”, as more than half of skilled worker visas over the past couple of years have gone to dependents.

“However, there’s no data on how many of them would have passed a language test so it is hard to say how big,” Dr Sumption added.

The Home Office has not put a figure on what sort of reduction these policies could achieve, with Ms Cooper to give more details in parliament on Monday afternoon.

Please use Chrome browser for a more accessible video player

Minister reveals new immigration plans

On Sunday, she told Sky News’s Trevor Phillips that plans to close the care worker visa route and change the skilled visa threshold to require a graduate qualification would cut the number of overseas workers by about 50,000 this year.

Read More:
Labour’s shift on migration may assuage voters’ concerns – but risks impacting struggling care sector
Care workers plead for higher salaries amid recruitment crisis

However, she refused to put a target on the overall levels of net migration the government is aiming for, saying that approach “failed” under the Conservatives.

The Tories have admitted making mistakes in office, but are still calling for a binding immigration cap and want to repeal the Human Rights Act for immigration issues.

Shadow Home Secretary Chris Philp said Labour has “overseen the worst ever start to a year for illegal immigrants crossing the channel” adding: “The idea that Starmer is tough on immigration is a joke.”

Continue Reading

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