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We continue our discussion of sexually transmitted infections
with the human immunodeficiency virus.
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HIV infection is a sexually transmitted or blood-borne retroviral infection
characterized by gradual decline and cell-mediated immune function,
and complicated by a wide variety of opportunistic microbial infections and cancers.
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As you can see from this global map,
the prevalence of HIV infection is definitely worldwide
and notice the heavy concentration in Southern Africa.
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In certain countries in Southern Africa,
approximately one in every 4 to 5 people you meet is HIV-positive.
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This is a predominantly sexually transmitted infection among heterosexuals,
among men who have sex with men, and among bisexuals.
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And there is an alarming increase in infections among black women.
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Persons with intravenous drug use comprise about 7 percent of the infections.
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In 2022, there were 39 million persons infected,
in approximately in equal ratio between males and females.
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More than two-thirds of HIV infections worldwide are in sub-Saharan Africa.
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And there, it is primarily a heterosexual transmission problem
because homosexuality is a taboo in many African countries.
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It can also be spread to innocent victims like mother to child.
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Pregnant women can spread it to their babies, either in utero, at delivery,
or through breastfeeding after delivery.
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Let’s talk a little bit about the virus itself.
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HIV is an RNA retrovirus.
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And what that means is that it is capable, once getting into a target cell,
of making a DNA copy of itself.
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It kind of goes retrograde from RNA to DNA.
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We’ll talk more about how that happens shortly.
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And there are essentially two types of the human immunodeficiency virus.
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HIV1 is actually closely related to a chimpanzee simian immunodeficiency virus, SIV.
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And there are 4 distinct groups of HIV1 – M, N, O, and P.
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M is responsible for the vast majority of cases
and M is responsible for the pandemic of HIV that we now see.
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HIV2 is closely related to another simian immunodeficiency virus.
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And it’s pretty confined to West Africa.
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There’s not ever been a pandemic of HIV2.
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Mother to infant transmission does not seem to occur.
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And although some patients can get AIDS with HIV2, most do not progress to AIDS.
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And I want you to focus on this cartoon of the virus.
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And I think you can see that it has some spikes on the circumference.
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These are in virology terminology called peplomers,
and notice that they are comprised of glycoproteins – gp120 and gp41.
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gp120 is the outermost glycoprotein
and it is what helps the virus dock with the target cell.
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gp41 is the part that actually fuses to the human cell membrane - keep that in mind.
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Inside the virus, you have two copies of the viral RNA.
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And the little red dot signifies an important enzyme known as reverse transcriptase.
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It is this enzyme, which enables the virus to make a DNA copy of itself.
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This infection is transmitted primarily person to person through sex,
but it also can occur from mother to child during delivery
and contact with the blood of an infected person.
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The exact cell type that is infected first is unclear.
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What seems to happen is that there’s a break in the genital mucosa,
a break in the skin, and then the virus infects a dendritic cell,
which then is carried to other cells that have this molecule, called the CD4 molecule.
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Examples of cells that have that are the macrophage, T helper cells,
and that’s necessary but not sufficient.
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In other words, the virus can attach to this CD4 molecule, but it needs something else,
and that is a chemokime receptor.
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And the chemokime receptors are the way
that white cells essentially talk to one another.
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We’re talking here about CCR5 and CXCR4.
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These are two chemokime receptors
that determine whether the virus is going to enter the cell.
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So what happens is these outer glycoprotein, gp120, docks with the CD4 molecule
and a chemokime receptor, either CCR5 or CXCR4.
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And once it attaches to those chemokime receptors,
there’s a twist – a conformational change exposing this fusion domain,
which is present on gp41,
and that allows the HIV membrane to fuse with the human cell membrane.
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And that is the way that the virus gets into the cell after it fuses.
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So there is a class of drugs that actually can block at this step called fusion inhibitors.
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Anyway, once the virus gets into the cell, it’s got to uncoat.
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And it uncoat and unloads its two copies of positive-sense RNA,
and this is where the HIV reverse transcriptase kicks in.
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It makes a DNA copy of itself, and now it's viral DNA,
and that is what integrates into the cell chromosome.
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That’s what gets into our DNA.
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And so, reverse transcriptase inhibitors are going to block this retroviral change
from RNA to DNA.
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Now, human DNA is then integrated into the human chromosome.
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It gets into our DNA, and this is where integrase inhibitors work.
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Then HIV DNA starts making its own messenger RNA at our ribosomes.
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It kind of commandeers our ribosomes and makes the components of new HIV.
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And then the new HIV virions emerge from an infected cell,
and initially they are immature.
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And then they become mature,
and this is where protease inhibitors prevent this maturation step.
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Protease inhibitors, as you know,
are one of the important forms of antiviral chemotherapy.
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And the cells die as a result of this infection.
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And they die in enormous numbers –
tenth to the ninth CD4 T-cells are killed by this virus every day.
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And as the virus is released from a CD4 cell, it attacks new CD4 T-cells.