HIV Pathophysiology (3/3) - Disease Progression

There are three stages of HIV infection: the acute infection, the chronic or latent phase, and AIDS. The acute infection begins when HIV enters the body and establishes an infection. Some people get no symptoms during this period, though typically, there will be flu-like or mononucleosis-like symptoms that decline over 1-2 months. Initially, replication occurs within immune cells at the site of infection, or in peripheral blood mononuclear cells. At the start of the infection process, HIV is usually R5-tropic (or M-tropic). Viral tropism is viral preference for particular coreceptors. M-tropic HIV is a strain of HIV that enters and infects cells that have CCR5 coreceptors - so again, T-cells, macrophages, monocytes, and dendritic cells. HIV is infamous for its high rate of mutation. HIV’s RNA is ~9200 nucleotide bases long, and reverse transcriptase introduces a mutation about once per 2000 incorporated nucleotides. With the rate of viral replication being so high, a second strain of virus sometimes develops - X4-tropic, or T-tropic HIV. T-Tropic HIV binds to the CXCR4 coreceptor, which is found exclusively on T-cells. This is very bad news, as it speeds up viral progression. M-tropic and T-tropic strains can coexist in the body.
There is also another reason why HIV might start off as M-Tropic and eventually develop into a T-Tropic strain. CCR5 is generally expressed by memory T-cells, while CXCR4 is expressed by naïve CD4 T-cells. Normally, memory cells divide about ten times faster than naïve CD4 T-cells. Hence, T-tropic virus would hence be disadvantaged during early infection. However, as the disease progresses, naïve cell division is as frequent as that of memory cells. That is when there tends to be a shift in tropism.
Sentinel dendritic cells in mucosal tissue are one of the first cell populations HIV encounters during sexual transmission. They are important in establishing a successful host infection from a small viral pool.
The bulk of CD4+ T-cell loss occurs in the first few weeks post-infection. The greatest casualties occur in the intestinal mucosa, where most of the body’s lymphocytes occur and where the majority of T-cells express the CCR5 co-receptor. There is now a big spike in HIV replication and the amount of virus in the patient’s blood. At this time, there can be several million viral particles per mL of blood and a large drop in circulating helper T-cells. This acute viremia - in other words, virus presence in the blood - typically results in the activation of the CD8+ cytotoxic T-cells, as well as B cells. The cytotoxic T-cells kill infected cells and B-cells produce antibodies. This counter attack lowers the amount of viral replication. T-cell counts rebound, though not to pre-infection levels. The infected individual now enters the chronic phase.
During the chronic stage, little virus is detectable in the peripheral blood. However, HIV continues to replicate, causing general immune activation. Dendritic cells secrete inflammatory cytokines and interferons, which alter T-cell proliferation and differentiation, contributing to the immune dysregulation characteristic of the chronic stage. However, the immune response to HIV is not strong enough to stop viral replication from continuing within lymphoid tissues.
Reasons for dropping CD4+ T-cell counts differ in the acute and chronic stages. After initial infection, T-cell depletion results from HIV-induced cell lysis and the killing of infected cells by cytotoxic T-cells. However, at the chronic stage, generalized immune activation, combined with the gradual loss of the ability of the immune system to generate new T-cells results in a slow decline in T-cell numbers.
And now we come to the final stage of HIV infection - AIDS. A healthy level of T-cells is 500-1600 cells/mL! When T-cell levels fall below 200 cells per mm3, the immune system is severely compromised. With emergence from latency, there is a loss of normal lymph node architecture, resulting in persistent generalized lymphadenopathy. Opportunistic infections become common. Apart from weight loss, chills, fatigue, and a persistent fever, AIDS patients suffer from constant diarrhea from infectious parasites, recurring pneumonia, and fungal infections. Certain cancers that are normally rare, such as Kaposi’s sarcoma and non-Hodgekin lymphoma, start to cause lesions of skin and other soft tissues. In the end, people don’t die from HIV. They die from infections that a healthy immune system would fight off.
3D models from: www.turbosquid.com/FullPrevie...
www.cgtrader.com/3d-models/ch...
HIV graph based on: en.wikipedia.org/wiki/HIV#/me...

[@edumasterorco]

I was looking for that tropism explanation, thank you!

[@priestiseghehi]

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[@johnlewiskodhek]

Thanks for this. Amazing coverage

[@elpenevchitsu6365]

Is RNA can detect HIV in chronic infection ? (In my case 88days after exposure)

[@_elenaio_]

Very interesting - thank you

[@priestiseghehi]

I got cured from hpv warts through herbal treatment from Dr Iseghehi who I met through the internet, I actually couldn't believe it at first because it sounded impossible to me knowing how far I have gone just to get rid of it. Dr Iseghehi send me his herbal medicine which I took as instructed and here I am living a happy life once again, a big thanks to Dr Iseghehi, I am sure there are many herbal doctors out there but Dr Iseghehi did it for me, contact him [e-mail] or WhatsApp [phone] He is capable of curing HIV/AIDS, HERPES, HPV, HSV1&2, CANCER of all kinds, DIABETES and so many other infections.
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[@moongirl6128]

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[@JuanDiazSilvermyst]

4th gen test can now detect HIV must faster and medication has come a long way. We still need a cure for this horrible virus. I hope hope HOPE they find one.

[@Me-the-One-G]

Every time cd4 deplay down to 1000 or can be mentained or come back over 1000 in hiv accute phase?!

[@priestiseghehi]

I got cured from hpv warts through herbal treatment from Dr Iseghehi who I met through the internet, I actually couldn't believe it at first because it sounded impossible to me knowing how far I have gone just to get rid of it. Dr Iseghehi send me his herbal medicine which I took as instructed and here I am living a happy life once again, a big thanks to Dr Iseghehi, I am sure there are many herbal doctors out there but Dr Iseghehi did it for me, contact him [e-mail] or WhatsApp [phone] He is capable of curing HIV/AIDS, HERPES, HPV, HSV1&2, CANCER of all kinds, DIABETES and so many other infections.
Facebook page👇🏻👇🏻👇🏻👇🏻
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[@sofiacalero7100]

Very helpful

[@priestiseghehi]

I got cured from hpv warts through herbal treatment from Dr Iseghehi who I met through the internet, I actually couldn't believe it at first because it sounded impossible to me knowing how far I have gone just to get rid of it. Dr Iseghehi send me his herbal medicine which I took as instructed and here I am living a happy life once again, a big thanks to Dr Iseghehi, I am sure there are many herbal doctors out there but Dr Iseghehi did it for me, contact him [e-mail] or WhatsApp [phone] He is capable of curing HIV/AIDS, HERPES, HPV, HSV1&2, CANCER of all kinds, DIABETES and so many other infections.
Facebook page👇🏻👇🏻👇🏻👇🏻
facebook.com/Doctor-Iseghehi-104229071464613/?ref=your_pages

[@pathology9042]

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[@pathology9042]

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[@pathology9042]

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[@vid.ot5.ot7]

Can i please have the source of this information??

[@priestiseghehi]

I got cured from hpv warts through herbal treatment from Dr Iseghehi who I met through the internet, I actually couldn't believe it at first because it sounded impossible to me knowing how far I have gone just to get rid of it. Dr Iseghehi send me his herbal medicine which I took as instructed and here I am living a happy life once again, a big thanks to Dr Iseghehi, I am sure there are many herbal doctors out there but Dr Iseghehi did it for me, contact him [e-mail] or WhatsApp [phone] He is capable of curing HIV/AIDS, HERPES, HPV, HSV1&2, CANCER of all kinds, DIABETES and so many other infections.
Facebook page👇🏻👇🏻👇🏻👇🏻
facebook.com/Doctor-Iseghehi-104229071464613/?ref=your_pages

[@shaunlally3986]

A cure asap pls

[@elpenevchitsu6365]

Is RNA PCR can detect HIV at 88 days after exposure?

[@arbazpatel5949]

Yes

[@marcfavell]

You should do a video SARS2 🦠 because I believe we are at the denial stage of AIDS 2.0 but only this time 70% of the world's infected 😢
Crazy the similarities I'll tell you that