HIV & AIDS - signs, symptoms, transmission, causes & pathology

Summary

The script explains HIV, focusing on its two types, HIV-1 and HIV-2, with HIV-1 being more prevalent. It details how HIV targets CD4+ cells, using gp120 to bind and enter cells, and replicates by integrating into the host's DNA. The video outlines the progression from acute infection to AIDS, highlighting the immune system's decline and the emergence of AIDS-defining conditions. It also covers transmission modes and the importance of HIV testing and antiretroviral therapy in managing the disease, emphasizing the lack of a cure but the potential for a healthier life with treatment.

Takeaways

• 😷 HIV is a virus that attacks the immune system, leading to immunodeficiency and increasing the risk of infections and tumors.
• 🌐 HIV-1 is the primary cause of AIDS globally, while HIV-2 is rare and mostly found in western Africa and southern Asia.
• 🔬 HIV targets CD4+ cells, including macrophages, T-helper cells, and dendritic cells, which are crucial for immune response.
• 🔗 The virus enters cells by binding to the CD4 molecule and a co-receptor, typically CCR5 or CXCR4, using its gp120 protein.
• 🧬 Some individuals have genetic mutations in CCR5 that confer resistance to HIV, as the virus cannot enter cells lacking these receptors.
• 📚 HIV is a retrovirus that uses reverse transcriptase to convert its RNA into proviral DNA, which integrates into the host's genome.
• 📈 After acute infection, HIV enters a chronic phase where it continues to replicate and mutate, potentially leading to an X4 strain targeting T-cells more aggressively.
• 🩺 HIV infection progresses to AIDS when T cell counts drop significantly, leading to severe immunodeficiency and life-threatening infections.
• 💉 There is no cure for AIDS, but antiretroviral therapy (ART) can manage the condition, slowing viral replication and allowing the immune system to recover.
• 🩸 HIV is primarily transmitted through sexual intercourse, but can also spread via intravenous drug use, mother-to-child transmission, and less commonly, through needlesticks and blood products.

Q & A

What is HIV and how does it affect the immune system?

HIV, or human immunodeficiency virus, targets cells in the immune system, particularly CD4+ cells like macrophages, T-helper cells, and dendritic cells. Over time, it leads to immunodeficiency, increasing the risk of infections and tumors that a healthy immune system would normally fend off.

What are the two types of HIV and which is more common?

There are two types of HIV: HIV-1 and HIV-2. HIV-1 is more commonly associated with AIDS globally, while HIV-2 is rarer and typically found in western Africa and southern Asia.

How does HIV enter and infect cells?

HIV enters cells by binding to the CD4 molecule on the cell membrane via a protein called gp120. It also needs to bind to a co-receptor, either CCR5 or CXCR4, to gain entry into the cell.

What is the significance of the CCR5 co-receptor in HIV infection?

The CCR5 co-receptor is significant because some individuals with genetic mutations in CCR5 have resistance to HIV. This is because HIV cannot attach and enter the cell without the co-receptor.

How does HIV replicate within the host cell?

HIV is a retrovirus that injects its single-stranded RNA into the host cell. It uses an enzyme called reverse transcriptase to transcribe this RNA into proviral DNA, which is then integrated into the host's DNA. When the immune cell is activated, it inadvertently transcribes and translates new HIV viruses.

What is the difference between the acute and chronic phases of HIV infection?

During the acute phase, there is a rapid increase in viral replication leading to flu-like symptoms. In the chronic phase, the immune system is steadily weakened as HIV continues to replicate, leading to a slow decline in T cell counts and an increase in viral load.

What is the significance of the X4 strain of HIV?

The X4 strain of HIV targets the CXCR4 coreceptor, which is primarily found on T-cells. It can lead to a more aggressive destruction of CD4 T cells, potentially accelerating the progression to AIDS.

How does HIV progress to AIDS?

HIV progresses to AIDS when the immune system becomes severely compromised, typically when T cell counts fall below 200 cells/mm3. At this stage, the body is vulnerable to opportunistic infections and certain cancers.

What are the most common modes of HIV transmission?

The most common modes of HIV transmission are sexual intercourse, intravenous drug use, and mother-to-child transmission. Less common modes include accidental needlesticks and use of blood products.

What are the different types of HIV tests available?

HIV tests include antibody tests, antibody/antigen tests, and RNA/DNA tests. The antibody/antigen test is recommended for screening due to its ability to identify early infection.

How is HIV treated, and what is the goal of treatment?

HIV is treated with antiretroviral therapy (ART), which is a combination of medicines that slow down HIV replication, allowing the immune system to recover and fight off infections more effectively.

Outlines

00:00

🦠 Understanding HIV and Its Impact on the Immune System

HIV is a virus that attacks the immune system, particularly CD4+ cells like macrophages, T-helper cells, and dendritic cells. It binds to the CD4 molecule and a co-receptor (CCR5 or CXCR4) to enter cells. HIV is an RNA retrovirus that uses reverse transcriptase to convert its RNA into DNA, which then integrates into the host cell's genome. Once inside, it hijacks the cell's machinery to replicate, leading to the production of new viruses that can infect more cells. The virus mutates frequently, creating different strains with varying tropisms. After initial infection, there's an acute phase with flu-like symptoms, followed by a chronic phase where the virus slowly depletes T cells. If left untreated, this can progress to AIDS, characterized by severe immunodeficiency and susceptibility to opportunistic infections and tumors.

05:00

🩺 HIV Infection Progression and Transmission Modes

The progression of HIV infection begins with a significant drop in T cell count during the acute phase, followed by a chronic phase where the virus continues to undermine the immune system. Some patients may develop an X4 strain targeting T-cells more aggressively. As T cell counts decline, patients experience symptoms like swollen lymph nodes and minor infections. Below 200 cells/mm3, the condition becomes AIDS, with severe symptoms and increased risk of opportunistic infections. Transmission modes include sexual intercourse, intravenous drug use, mother-to-child, and less commonly, through needlesticks or blood products. Diagnosis involves antibody, antigen, RNA, or DNA tests, with antibody/antigen tests being the initial screening method. There's no cure, but antiretroviral therapy (ART) can manage the disease, slowing viral replication and allowing the immune system to recover, thus improving quality and longevity of life and reducing transmission risk.

Keywords

💡HIV (Human Immunodeficiency Virus)

HIV is a virus that attacks the immune system, specifically CD4+ cells, which include macrophages, T-helper cells, and dendritic cells. It is the virus responsible for causing AIDS. In the script, HIV is described as having two types, HIV-1 and HIV-2, with HIV-1 being the primary cause of AIDS globally. Understanding HIV is central to the video's theme of explaining how the virus leads to immunodeficiency and the subsequent development of AIDS.

💡Immunodeficiency

Immunodeficiency refers to a weakened state of the immune system, which in the context of HIV, results from the virus targeting and damaging CD4+ cells. This leads to an increased susceptibility to infections and tumors, as the immune system can no longer effectively fight off pathogens. The video emphasizes the progression from HIV to immunodeficiency as a critical step towards the development of AIDS.

💡AIDS (Acquired Immunodeficiency Syndrome)

AIDS is the advanced stage of HIV infection, characterized by a severely compromised immune system, which makes the individual vulnerable to opportunistic infections and certain types of cancer. The video discusses AIDS as a complication that arises when the immune system fails due to HIV, leading to life-threatening conditions that a healthy immune system would normally prevent.

💡CD4+ cells

CD4+ cells are a type of white blood cell that plays a crucial role in the immune response. They have CD4 molecules on their surface, which HIV uses to attach and enter the cells. The video explains that HIV's targeting of CD4+ cells is a key mechanism in the virus's ability to cause immunodeficiency and AIDS.

💡gp120

gp120 is a protein found on the surface of HIV that enables the virus to attach to the CD4 molecule on host cells. This attachment is a necessary step for HIV to infect cells. The video uses gp120 as an example of how HIV gains entry into immune cells, highlighting the virus's strategy for evading the immune system.

💡Co-receptor

A co-receptor is a molecule that HIV uses in addition to the CD4 molecule to enter a cell. The most common co-receptors are CXCR4 and CCR5. The video explains that HIV needs to bind to both CD4 and a co-receptor to infect a cell, and it discusses how genetic mutations in the CCR5 co-receptor can provide resistance to HIV infection.

💡Retrovirus

A retrovirus is a type of virus that contains RNA and uses an enzyme called reverse transcriptase to convert its RNA into DNA, which is then integrated into the host cell's genome. The video describes HIV as a retrovirus, emphasizing its unique replication mechanism that involves reverse transcription and integration into the host's DNA.

💡Viral tropism

Viral tropism refers to the preference of a virus for specific types of cells or tissues. The video mentions that HIV can mutate and create strains with different tropisms, which can affect which cells they target within the host. Understanding viral tropism is important for grasping how HIV can adapt and cause varying degrees of damage to the immune system.

💡Antiretroviral Therapy (ART)

ART is a treatment for HIV that involves a combination of medicines to slow down the replication of the virus, allowing the immune system to recover and function more effectively. The video discusses ART as the primary treatment for HIV, highlighting its role in helping individuals with AIDS live longer, healthier lives and reduce transmission risks.

💡AIDS-defining conditions

AIDS-defining conditions are specific infections and cancers that signal the progression to AIDS, indicating a severely compromised immune system. The video lists conditions such as recurrent bacterial pneumonia, pneumocystis pneumonia, and certain types of tumors as examples of AIDS-defining conditions, illustrating the severe health risks associated with advanced HIV infection.

💡Transmission

Transmission refers to the ways in which HIV is spread from one individual to another. The video outlines various modes of transmission, including sexual intercourse, intravenous drug use, mother-to-child transmission, and less common modes like accidental needlesticks. Understanding transmission is crucial for preventing the spread of HIV.

Highlights

HIV targets cells in the immune system, leading to immunodeficiency and increased risk of infections and tumors.

There are two types of HIV: HIV-1, the most common worldwide, and HIV-2, which is rarer and mostly found in West Africa and South Asia.

HIV targets CD4+ cells, such as macrophages, T-helper cells, and dendritic cells, using the CD4 molecule and co-receptors like CCR5 and CXCR4.

Mutations in the CCR5 co-receptor can make some individuals resistant or slow the progression of HIV infection.

HIV is a retrovirus that uses reverse transcriptase to convert its RNA into proviral DNA, which integrates into the host’s genome.

When immune cells are activated by infections, HIV hijacks the cell’s machinery to produce more viruses, spreading the infection.

HIV mutations during replication result in different strains with varying viral tropism, which can target different immune cells.

The R5 strain of HIV, which uses the CCR5 co-receptor, is commonly involved in initial infection, spreading via macrophages and dendritic cells.

Acute HIV infection can cause flu-like symptoms, followed by a chronic phase lasting 2-10 years where the immune system is gradually weakened.

During the chronic phase, T-cell levels drop steadily, leading to an increased risk of infections such as tuberculosis.

As T-cell counts fall below 200 cells/mm3, HIV progresses to AIDS, causing severe immune system compromise and vulnerability to opportunistic infections.

AIDS-defining conditions include infections like pneumocystis pneumonia, fungal infections, and cancers such as Kaposi sarcoma.

HIV is primarily transmitted through sexual contact, with male-to-male transmission being the most common in the US and male-to-female transmission in resource-limited settings.

Antibody/antigen tests are recommended for HIV screening, with confirmatory tests needed if initial results are positive.

Although there is no cure for HIV, antiretroviral therapy (ART) can slow viral replication, allowing the immune system to recover and reducing transmission risk.

Transcripts

HIV, or human immunodeficiency virus, is a virus that targets cells in the immune system.

Over time, the immune system begins to fail which is called immunodeficiency, and this

increases the risk of infections and tumors that a healthy immune system would usually

be able to fend off.

These complications are referred to as AIDS, or acquired immunodeficiency syndrome.

Now there are two distinct types of HIV—HIV-1 and HIV-2.

HIV-1 is the more commonly associated with AIDS in the US and worldwide, HIV-2 is more

rare, and typically restricted to areas in western Africa and southern Asia.

HIV-2 is so uncommon that “HIV” almost always refers to HIV-1.

Alright HIV targets CD4+ cells, meaning cells that have this specific molecule called CD4

on their membrane.

Macrophages, T-helper cells, and dendritic cells are all involved in the immune response

and all have CD4 molecules; therefore they can be targeted by HIV.

The CD4 molecule helps these cells attach to and communicate with other immune cells,

which is particularly important when the cells are launching attacks against foreign pathogens.

So this little molecule is pretty important for our immune system, but it’s also extremely

important for HIV.

HIV targets and attaches to the CD4 molecule via a protein called gp120 found on its envelope.

HIV then again uses gp120 to attach to another receptor, called a co-receptor.

HIV needs to bind to both the CD4 molecule and a coreceptor to get inside the cell.

The most common co-receptors that HIV uses are the CXCR4 co-receptor, which is found

mainly on T-cells, or the CCR5 co-receptor which is found on T-cells, macrophages, monocytes,

and dendritic cells.

These coreceptors are so important that some people with homogeneous genetic mutations

in their CCR5 actually have resistance or immunity to HIV, since HIV can’t attach

and get into the cell.

In fact, even heterozygous mutations which lead to fewer co-receptors on the cells, can

make it harder for the virus to spread, and results in a slower disease progression.

For those without this mutation though, once HIV binds to CD4 and either CCR5 or CXCR4,

it gains access to the cell.

HIV is a single-stranded, positive-sense, enveloped RNA retrovirus, meaning that it

injects its single strand of RNA into the T-helper cell.

The “retro” part of retrovirus isn’t referring to its style, but refers to it needing

to use an enzyme called reverse transcriptase to transcribe a complementary double-stranded

piece of “proviral” DNA.

Proviral just means that it’s ready to be integrated into the host’s DNA, so it enters

the T-helper cell’s nucleus and pops itself into the cell’s DNA, ready to be transcribed

into new viruses, pretty sneaky, huh?

Well here’s the actual sneaky part—when the immune cells become activated, they start

transcribing and translating proteins needed for the immune response.

Ironically, this means that whenever the immune cell is exposed to something that causes it

to start up an immune response, like any infection, the immune cell ends up inadvertently transcribing

and translating new HIV viruses, which bud off from the cell membrane to infect more

cells.

Very sneaky indeed!

One thing to know is that HIV is notorious for making errors when it replicates and that

during an infection it can mutate to create slightly different strains of viruses.

These viruses are all still considered “HIV” but behave slightly differently from each

other and target different cells in the host, in fact that host cell preference is called

viral tropism.

So let’s start with HIV entering the body through sexual intercourse which is how it

typically spreads from person to person.

At this early point, during what we call acute infection, the R5 strain of HIV, which bind

to the CCR5 coreceptor will get into macrophages, dendritic cells, and T cells.

Usually dendritic cells hanging out in the epithelial or mucosal tissue where the virus

entered the body, capture the virus and migrate to the lymph nodes, where a lot of immune

cells live, and the R5 strain of HIV essentially has a field day, infecting T-helper cells,

macrophages, and more dendritic cells, which leads to a big spike in HIV replication and

the amount of virus found in the patient’s blood.

Patients typically experience flu-like or mononucleosis-like symptoms during the acute

infection.

In response, the immune system mounts a counterattack, and starts to control the amount of viral

replication, and the amount of virus in the blood declines to lower but still detectable

levels by 12 weeks—at which point the patient enters the chronic or clinically-latent phase,

which can last between 2 and 10 years.

If we also plot the amount of T cells alongside the amount of virus, we’ll see that they

loosely mirror each other, which makes total sense, right?

Initially you have a considerable decline in the acute phase until the immune system

mounts its counterattack.

After this point, even though there may not be any clinical signs or symptoms of the virus,

the virus is steadily chipping away at the immune system, and the number of viruses in

the blood slowly increases, while at the same time T cells slowly decrease, losing about

1-2 billion T cells every day.

During this chronic phase, T cell counts usually remain above 500 cells / mm3, about the size

of the head of a pin, and patients can still fight off other infections fairly well, although

some infections like tuberculosis become more common and severe.

Remember how HIV replication can create mutations?

Well during the chronic phase of HIV infection, it’s worth pointing out that some patients

develop an X4 strain of HIV which targets the CXCR4 coreceptor, which is essentially

only T-cells.

These X4 strains kind of lay low in the lymphoid tissues, and steadily destroy of CD4 T cells,

since about 90% of T cells are found in lymphoid tissue.

Not all patients develop the X4 strain, though, so it’s not completely clear what the presence

of this strain implies about the disease course.

When the body’s T cells drop low enough, between about 200 and 500 cells / mm3, patients

start experiencing symptoms like swollen lymph nodes, or lymphadenopathy, as well as relatively

minor infections like oral hairy leukoplakia, a hairy-looking white patch on the side of

the tongue caused by the same Epstein-Barr virus that causes mononucleosis, as well as

oral candidiasis, a yeast infection in the mouth.

As more T cells are lost, and the level falls below 200 cells / mm3, the immune system becomes

severely compromised and at this stage the condition has progressed from HIV disease

to AIDS.

At this point people experience things like persistent fever, fatigue, weight loss, and

diarrhea.

And the HIV count in the blood might increase significantly.

At this point, certain conditions start to develop that are said to be “AIDS-defining”,

such as recurrent bacterial pneumonia, pneumocystis pneumonia, and fungal infections like candidiasis

of the esophagus.

Other conditions include certain tumors and malignancies like Kaposi sarcoma which causes

lesions on the skin and other soft tissues, and primary lymphoma of the brain.

Many people with AIDS die from infections that a healthy immune system would typically

be able to fend off, like pneumocystis, cytomegalovirus, or mycobacterium avium complex.

Male-to-male transmission is the most common mode of transmission in the US, and male-to-female

is the most common mode in resource-limited settings.

Although less common, female-to-male transmissions occur as well since HIV is present in the

vaginal and cervical fluids of infected women.

In fact, over 75% of all cases of HIV are contracted from sexual intercourse.

The next most common means of transmission include things like intravenous drug abuse

and mother-to-child transmission, which can be via the placenta during delivery, or via

breast milk.

Other, much less common modes of transmission include accidental needlesticks, and use of

blood products like blood transfusions.

As far diagnosis goes, there are a few types of HIV tests that can be done—antibody tests,

antibody/antigen tests, and RNA/DNA tests.

Antibody tests look for antibodies that the body’s made against HIV.

Antigen tests look for the virus directly, so antibody/antigen tests detect both antibodies

to the virus as well as the virus itself.

RNA tests screen for viral RNA, so they also detect the virus directly, and DNA tests look

for copies of the viral RNA (since remember it’s a retrovirus so it copies its genetic

material into DNA).

For screening purposes, the recommended test is the antibody/antigen test, which is better

at identifying early infection.

It’s also recommended, if the first test is positive, to follow it with a confirmatory

test that looks for antibody or nucleic acids.

There’s currently no cure for AIDS; treatment however, can help somebody with AIDS live

longer, healthier lives and help reduce the risk of transmission.

The primary method is to use antiretroviral therapy, or ART.

ART isn’t a single medicine, but a combination of medicines that’s known as an HIV regimen.

These help slow down HIV replication, which gives the immune system a chance to recover

and help fight off other infections more effectively.