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<title>HIV Infection</title></titleStmt>

<publicationStmt><distributor>BASE and Oxford Text Archive</distributor>


<availability><p>The British Academic Spoken English (BASE) corpus was developed at the

Universities of Warwick and Reading, under the directorship of Hilary Nesi

(Centre for English Language Teacher Education, Warwick) and Paul Thompson

(Department of Applied Linguistics, Reading), with funding from BALEAP,

EURALEX, the British Academy and the Arts and Humanities Research Board. The

original recordings are held at the Universities of Warwick and Reading, and

at the Oxford Text Archive and may be consulted by bona fide researchers

upon written application to any of the holding bodies.

The BASE corpus is freely available to researchers who agree to the

following conditions:</p>

<p>1. The recordings and transcriptions should not be modified in any


<p>2. The recordings and transcriptions should be used for research purposes

only; they should not be reproduced in teaching materials</p>

<p>3. The recordings and transcriptions should not be reproduced in full for

a wider audience/readership, although researchers are free to quote short

passages of text (up to 200 running words from any given speech event)</p>

<p>4. The corpus developers should be informed of all presentations or

publications arising from analysis of the corpus</p><p>

Researchers should acknowledge their use of the corpus using the following

form of words:

The recordings and transcriptions used in this study come from the British

Academic Spoken English (BASE) corpus, which was developed at the

Universities of Warwick and Reading under the directorship of Hilary Nesi

(Warwick) and Paul Thompson (Reading). Corpus development was assisted by

funding from the Universities of Warwick and Reading, BALEAP, EURALEX, the

British Academy and the Arts and Humanities Research Board. </p></availability>




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<langUsage><language id="en">English</language>



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<personGrp role="speakers" size="16"><p>number of speakers: 16</p></personGrp>





<item n="speechevent">Lecture</item>

<item n="acaddept">Biological Sciences</item>

<item n="acaddiv">ls</item>

<item n="partlevel">UG3</item>

<item n="module">Advanced Virology</item>




<u who="nm0607"><kinesic desc="projector is on showing slide" iterated="n"/> right then <pause dur="0.4"/> okay that's great <pause dur="0.8"/> yeah so i said in Finland <pause dur="0.8"/> about thirty per cent of cases are only thirty per cent of cases are acquired out of country and the rest acquired in country <pause dur="1.5"/> so the next thing <kinesic desc="changes slide" iterated="n"/> i want to show you is the <pause dur="1.6"/> it says the situation in the U-K <pause dur="0.6"/> # <pause dur="0.5"/> current situation in the U-K <pause dur="1.3"/> # that's a bit grim <pause dur="2.8"/> # <pause dur="1.5"/> i was just going to explain <pause dur="6.5"/><event desc="looks through slides" iterated="y" dur="25"/> you've got them in your handout </u><pause dur="0.3"/> <u who="sm0608" trans="pause"> yeah </u><u who="sf0609" trans="pause"> u-huh </u><u who="nm0607" trans="latching"><vocal desc="clears throat" iterated="n"/> <pause dur="4.7"/> now <pause dur="1.7"/> i haven't put them on this copy i can't get onto my hard disk it's # <pause dur="1.0"/> let's shut this off a minute and we'll talk about that when we move on </u><gap reason="break in recording" extent="uncertain"/> <u who="nm0607" trans="pause"> so if we look at the first table this this gives you the most up to date information for the U-K <pause dur="0.4"/> okay <pause dur="0.6"/> and what you can see is cumulatively <pause dur="1.6"/> at the end of last year <pause dur="1.4"/> about fifty-two-thousand people <pause dur="0.8"/> had been diagnosed or fifty-three-thousand almost fifty-three-thousand down in the bottom <pause dur="0.3"/> right-hand corner <pause dur="0.4"/> had been diagnosed with H-I-V <pause dur="1.0"/> and of those roughly thirty-thousand <pause dur="1.1"/> were homosexual spread <pause dur="1.2"/> men-men <pause dur="1.0"/> and roughly fifteen-thousand so

slightly under a third <pause dur="0.9"/> were <pause dur="0.2"/> heterosexual spread <pause dur="1.0"/> and then <pause dur="0.6"/> intravenous drug abuse comes next and then a relatively small number from blood products <pause dur="0.6"/> about a thousand just under a thousand mother to infant transmission and then a couple of thousand where it's not quite clear how the transmission occurred <pause dur="0.9"/> the thing that you should notice along the bottom <pause dur="1.1"/> is that up until around about ninety-ninety-seven <pause dur="1.0"/> the number of newly acquired infections each year is relatively stable <pause dur="1.0"/> and then it starts to accelerate again <pause dur="0.8"/> and in fact in the period September two-thousand-and-one to September two-thousand-and-two <pause dur="0.4"/> there's been some five-thousand-three-hundred <pause dur="0.4"/> new <pause dur="0.6"/> infections diagnosed <pause dur="1.4"/> so you can see that after a period of about ten years of relatively stable new infection rates <pause dur="1.2"/> the epidemic is <pause dur="0.4"/> in this country <pause dur="0.3"/> is increasing again <pause dur="0.2"/> not dramatically but it is going up at the rate of <pause dur="0.6"/> roughly <pause dur="0.8"/> fifteen to twenty per cent increased incidence a year <pause dur="2.8"/> and if you look at table

two <pause dur="2.3"/> what table two shows you is <pause dur="0.9"/> diagnosis by <pause dur="1.0"/> exposure category <pause dur="2.0"/> for <pause dur="0.6"/> just for one year just for the last year September <pause dur="0.5"/> two-thousand-and-one to September two-thousand-and-two <pause dur="2.5"/> and you can see that <pause dur="1.3"/> this <trunc>sh</trunc> this <pause dur="0.8"/> table shows you two things it shows you <pause dur="0.7"/> the distribution according to what type of category the infection was <pause dur="0.6"/> in so men-men <pause dur="0.6"/> and heterosexual spread and various subdivisions of heterosexual spread and you can see in there the figure that shows <pause dur="1.0"/> for heterosexual # <trunc>s</trunc> # spread acquired abroad <pause dur="0.7"/> no evidence of a high risk partner <pause dur="0.9"/> okay <pause dur="0.6"/> <trunc>acquir</trunc> U-K acquired no evidence of a high risk partner <pause dur="0.7"/> and you can see it broken down by region <pause dur="1.5"/> and the thing i want to come out of the broken down by region is you can see that both in terms of <pause dur="0.5"/> the acquired infections last year and the total number of infections acquired <pause dur="1.0"/> London is an epicentre <pause dur="1.3"/> yeah <pause dur="3.5"/> and then the final table i've given you <pause dur="3.1"/> is <pause dur="1.0"/> again <pause dur="0.2"/> year is is more total figures this is <pause dur="0.4"/> year of <trunc>infectio</trunc> <pause dur="0.5"/> year of infection over

the last ten years <pause dur="1.5"/> and the area where the infection was acquired <pause dur="0.3"/> or was diagnosed in fact not necessarily acquired <pause dur="0.5"/> and again what emerges from that is you can see that across the total epidemic of the <pause dur="0.3"/> fifty-odd-thousand cases <pause dur="0.8"/> some were over thirty-thousand thirty-two-thousand <pause dur="0.4"/> were acquired in the London area <pause dur="1.7"/> what that's telling you is <pause dur="0.4"/> even in the epidemic in this country <pause dur="0.7"/> the <pause dur="0.2"/> the risk <pause dur="0.3"/> varies according to where in the country you are <pause dur="0.7"/> okay and that would be true in most countries <pause dur="0.8"/> risk is not uniform <pause dur="1.3"/> okay and it's it's a it's an important message to get across to you <pause dur="2.7"/> okay <pause dur="0.8"/> so you can see the situation globally <pause dur="0.6"/> is we've got some forty-million people <pause dur="1.5"/> infected <pause dur="0.9"/> but actually the U-S-A the U-S the U-K's contribution to this forty-million <pause dur="0.5"/> is pretty small <pause dur="0.7"/> it's only fifty-two-thousand <pause dur="1.8"/> in fact it's less than fifty-two-thousand really because <pause dur="0.5"/> you're talking about <pause dur="0.5"/> a significant fraction of the fifty-two-thousand diagnosed cases in this country will already be

dead i can't remember <pause dur="0.4"/> what the total is it's around about thirty-thousand of them have already died <pause dur="0.8"/> so we're only contributing about twenty-thousand <pause dur="0.6"/> between twenty and thirty-thousand <pause dur="0.2"/> to that forty-million figure <pause dur="0.7"/> in this country <pause dur="1.6"/> okay <pause dur="1.4"/> all right that's all i'm going to say about the <pause dur="1.0"/> the epidemic <pause dur="0.8"/> okay <pause dur="0.7"/> the important message you've got to take across about the epidemic is <pause dur="1.1"/> it's a <trunc>c</trunc> huge global problem <pause dur="1.5"/> it's still an escalating <sic corr="global">grobal</sic> problem <pause dur="1.1"/> okay <pause dur="0.2"/> the numbers are going up rapidly they are not stable or going down <pause dur="0.7"/> okay <pause dur="0.6"/> and it's predominantly a problem in the developing world <pause dur="0.9"/> particularly sub-Saharan Africa <pause dur="0.7"/> where you've seen from some of the incidence figures i showed you in the last lecture <pause dur="0.5"/> that there are quite frightening consequences for social structures in some of those countries <pause dur="0.9"/> you know <pause dur="1.6"/> # <pause dur="0.4"/> less of a problem in the developed world more under control in the developed world <pause dur="1.1"/> more under more <trunc>un</trunc> control

more under control still in this country <pause dur="1.3"/> most of the spread in this country is still <pause dur="0.3"/> homosexual spread although heterosexual spread <pause dur="0.3"/> is the most rapidly growing <pause dur="0.2"/> category <pause dur="1.3"/> and most of that heterosexual spread <pause dur="0.5"/> is <pause dur="0.2"/> infection acquired <pause dur="0.2"/> out of the country <pause dur="1.0"/> so by somebody going from this country and having a sex partner <pause dur="0.3"/> in a country where the generalized epidemic is <trunc>a</trunc> is going on <pause dur="0.3"/> at a high level <pause dur="0.8"/> rather than spread within the country <pause dur="2.2"/> all right what i want to do now is move away from talking about the epidemic in a broad sense and start talking about <pause dur="0.5"/> the virus <pause dur="1.2"/> okay and the infection <pause dur="0.7"/> so we have another <pause dur="0.4"/> chunk of handouts and i'll try and get <pause dur="0.6"/> this up while you hand those around <pause dur="2.6"/><event desc="passes out handouts" iterated="n"/> if i can find me <pause dur="0.2"/> pointer again <pause dur="1.3"/> i've put the bally thing down <pause dur="0.2"/> here we go </u><gap reason="break in recording" extent="uncertain"/> <u who="nm0607" trans="pause"><kinesic desc="projector is on showing slide" iterated="n"/> right <pause dur="2.4"/> i hope you will already have seen a <trunc>v</trunc> <pause dur="0.2"/> a version of this sort of slide maybe not a precisely <pause dur="0.2"/> this but a version of this <pause dur="0.8"/> so this is the virus we're talking about H-I-V <pause dur="0.8"/> H-I-V <pause dur="0.3"/>

is a retrovirus to remind you <pause dur="0.6"/> what that means is that is that unusually for a <trunc>vir</trunc> <kinesic desc="changes slide" iterated="n"/> oops let me back up here <pause dur="7.2"/><kinesic desc="changes slide" iterated="n"/> oh <pause dur="0.2"/> bother <pause dur="5.1"/><kinesic desc="changes slide" iterated="n"/> unusually for a virus it has a diploid genome <pause dur="0.2"/> there are two pieces <pause dur="0.6"/> of single strand <pause dur="0.8"/> positive sense <pause dur="0.5"/> R-N-A <pause dur="0.4"/> contained within the virus particle <pause dur="5.1"/> the R-N-A is approximately ten kilobases in length <pause dur="0.6"/> just under ten kilobases in length <pause dur="2.0"/> it is <pause dur="0.5"/> it is surrounded <pause dur="2.0"/> by a <pause dur="0.6"/> capsid structure <pause dur="0.9"/> composed of <pause dur="0.6"/> a number of proteins <pause dur="0.6"/> P-twenty-four being the major protein <pause dur="0.9"/> and when H-I-V is diagnosed <pause dur="0.9"/> it is in fact antibodies against P-twenty-four <pause dur="1.2"/> that form the main basis of <pause dur="0.3"/> diagnosis <pause dur="2.8"/> so <pause dur="0.2"/> the bulk of H-I-V diagnosis does not involve <pause dur="0.3"/> looking directly for the agent itself for looking for the virus itself <pause dur="0.6"/> that usually comes <pause dur="0.3"/> as a confirmatory test <pause dur="0.8"/> the bulk of diagnosis is looking <pause dur="0.3"/> by looking for antibodies against this <pause dur="0.4"/> major structural protein <pause dur="0.9"/> P-twenty-four <pause dur="0.5"/> that makes up the inner capsid shell <pause dur="3.5"/> this <pause dur="0.6"/> capsid shell has a

toroid <pause dur="0.2"/> type of structure a sort of <pause dur="0.3"/> bit like a a flattened ended cone <pause dur="2.8"/> <trunc>m</trunc> <pause dur="0.7"/> on the R-N-A is the reverse transcriptase enzyme <pause dur="1.1"/> this is a retrovirus so which group in the Baltimore classification scheme is this in </u><pause dur="0.6"/> <u who="sm0610" trans="pause"> six </u><pause dur="2.2"/> <u who="nm0607" trans="pause"> didn't hear it very loud </u><pause dur="0.3"/> <u who="sm0610" trans="pause"> six </u><u who="nm0607" trans="latching"> six that's right six <pause dur="0.7"/> so it goes through a D-N-A intermediate so the first thing that it's got to do when it gets inside the infected cell is convert its <pause dur="0.5"/> single strand <pause dur="0.4"/> positive sense R-N-A <pause dur="0.5"/> into duplex D-N-A <pause dur="0.6"/> and it's transcription from that duplex D-N-A <pause dur="0.6"/> that gives rise to the viral messenger R-N-A <pause dur="2.5"/> the <pause dur="1.1"/> toroidal <pause dur="0.2"/> capsid is surrounded if i can ever find my pointer again there we go <pause dur="0.4"/> is surrounded by matrix protein <pause dur="0.7"/> shown <kinesic desc="indicates point on slide" iterated="n"/> here in green <pause dur="1.4"/> that's then surrounded by a lipid envelope <pause dur="0.3"/> so this is a lipid containing virus <pause dur="1.3"/> and embedded in that lipid envelope <pause dur="0.5"/> is the <pause dur="0.6"/> envelope

protein of the virus <pause dur="1.1"/> and the envelope protein is synthesized as a precursor <pause dur="3.7"/> called <kinesic desc="writes on board" iterated="y" dur="3"/> G-P-<pause dur="1.4"/>one-sixty <pause dur="1.5"/> the G-P standing for glycoprotein because this envelope <pause dur="0.7"/> protein <pause dur="0.5"/> is a glycoprotein <pause dur="1.2"/> and after synthesis G-P-one-sixty is cleaved <pause dur="0.8"/> to produce G-P-one-twenty <pause dur="1.0"/> which forms the head <pause dur="2.4"/> of the <pause dur="2.0"/> envelope protein sticking outside the lipid envelope <pause dur="1.9"/> and G-P-forty-one which is kind of like the stalk <pause dur="1.3"/> that through non-covalent interactions <pause dur="0.3"/> holds the <pause dur="0.3"/> G-P-one-twenty in place <pause dur="0.7"/> and the G-P-forty-one is a transmembrane protein it <pause dur="0.2"/> it goes through the lipid bilayer membrane <pause dur="2.0"/> okay <pause dur="1.0"/> down here at the bottom <pause dur="1.6"/><kinesic desc="indicates point on slide" iterated="n"/> is the gene organization <pause dur="0.3"/> of this virus <pause dur="2.1"/> and <pause dur="1.3"/> it's like any other retrovirus it <pause dur="0.6"/> but has some additional genes what genes do normal retroviruses carry </u><pause dur="1.9"/> <u who="sf0611" trans="pause"> gag pol and env </u><pause dur="1.0"/> <u who="sm0612" trans="pause"> gag pol and env </u><u who="nm0607" trans="latching"> gag pol and env and you can see here <pause dur="0.9"/><kinesic desc="indicates point on slide" iterated="n"/> gag <pause dur="1.3"/><kinesic desc="indicates point on slide" iterated="n"/> pol <pause dur="1.1"/> and <kinesic desc="indicates point on slide" iterated="n"/> env <pause dur="1.2"/> okay <pause dur="0.7"/> but H-I-V is unusual

in having a number of <trunc>othe</trunc> additional proteins usually referred to as accessory proteins <pause dur="3.1"/> and the degree to which we understand what these accessory proteins actually do for the virus <pause dur="0.5"/> varies according to which protein we are talking about <pause dur="1.5"/> so for example you will already have heard in this lecture series quite extensively about tat and rev <pause dur="1.0"/> tat and rev are involved in the regulation of gene expression by this virus <pause dur="0.9"/> okay <pause dur="0.7"/> but you won't have heard anything yet for example <pause dur="0.5"/> about vif <pause dur="1.4"/> okay <pause dur="0.8"/> vif is another accessory protein <pause dur="0.4"/> that overlaps <pause dur="0.3"/> the carboxy terminal end of the coding region of <pause dur="0.9"/> the R-T gene the polymerase gene <pause dur="0.7"/> and the amino terminal region of the V-P-R gene <pause dur="1.8"/> and vif stands for virus infectivity factor <pause dur="4.5"/> it's the protein that <trunc>m</trunc> <pause dur="0.3"/> of H-I-V that the limited amount of H-I-V work that i do that's the protein that we work on vif is an interesting protein <pause dur="0.5"/> in that <pause dur="1.7"/> as the name implies it's required <pause dur="0.6"/> for virus infectivity <pause dur="1.6"/> and if this protein is absent <pause dur="0.9"/> and you try and grow

virus in the <pause dur="2.5"/> normal host cells for this virus <pause dur="0.7"/> which are C-D-four-positive lymphocytes <pause dur="0.5"/> then the progeny virus that is produced is non-infectious <pause dur="4.5"/> it turns out <pause dur="0.7"/> that vif <pause dur="0.5"/> is actually required to overcome a normal cellular <pause dur="0.4"/> protein that's an inhibitory factor <pause dur="0.7"/> for H-I-V replication <pause dur="0.9"/> and i don't have time to go into the detail and anyway the detail is not pertinent to <pause dur="0.2"/> the rest of what i'm going to say <pause dur="1.0"/> so there are a number of accessory proteins down here <pause dur="1.4"/> and three <pause dur="0.4"/> major normal retrovirus proteins gag which <trunc>m</trunc> <pause dur="0.6"/> is a <pause dur="0.4"/> # <pause dur="1.2"/> is made as a polyprotein initially <pause dur="1.3"/> called <pause dur="3.2"/><kinesic desc="writes on board" iterated="y" dur="6"/> # <pause dur="3.0"/> P-R-fifty-five <pause dur="1.3"/> 'cause of the fifty-five kilodalton <pause dur="4.2"/> precursor <pause dur="1.0"/> and that precursor is cleaved through the action of a <pause dur="0.5"/> virion encoded protease gene <pause dur="1.6"/> that undertakes the major cleavages necessary to convert <pause dur="0.7"/> P-R-fifty-five <pause dur="1.0"/> into <pause dur="1.3"/> P-seventeen P-twenty-four P-six P-one P-seven a number of <pause dur="0.8"/> structural proteins that make up this <pause dur="0.3"/><kinesic desc="indicates point on slide" iterated="n"/> capsid shell here that i'm

pointing to <pause dur="2.9"/> okay <pause dur="1.5"/> so that's the virus we're talking about <pause dur="1.3"/> let's move on then to look at the pattern of this infection <pause dur="4.2"/><kinesic desc="changes slide" iterated="n"/> now you can divide H-I-V infection <pause dur="0.8"/> into three broad stages <pause dur="1.9"/> there's the primary infection <pause dur="2.3"/> which occurs over a few weeks <pause dur="2.6"/> there's a long period of what is usually called clinical latency <pause dur="2.9"/> and then there's the <pause dur="0.5"/> terminal stage of disease <pause dur="0.4"/> which we usually refer to as AIDS <pause dur="2.4"/> and the important point to see <kinesic desc="indicates point on slide" iterated="n"/> down here is the scale <pause dur="1.9"/> you can see that the primary infection <pause dur="0.7"/> occurs over a matter of weeks <pause dur="2.8"/> the latent period <pause dur="1.8"/> can be years <pause dur="0.8"/> there are certainly people around who have <pause dur="0.7"/> been well <pause dur="0.5"/> for more than a dozen years <pause dur="0.7"/> and then for some reason that's not entirely clear <pause dur="0.4"/> gone into full-blown AIDS <pause dur="2.5"/> the point about this <pause dur="1.3"/> is <pause dur="0.2"/> once you go into AIDS you are going to die <pause dur="1.2"/> okay <pause dur="1.7"/> you may you may be it may be possible to hold you <pause dur="0.9"/> through <pause dur="0.2"/> using antivirals that i'll talk about in a minute <pause dur="1.0"/> in <pause dur="0.2"/> in some sort of semblance of reasonable health for a period of time <pause dur="1.4"/> but for example <pause dur="0.5"/> when <pause dur="0.5"/>

A-Z-T zidovudine the main <pause dur="0.3"/> R-T antiviral inhibitor was <trunc>u</trunc> used extensively in the United States in monotherapy <pause dur="0.9"/> it improved your life expectancy as an AIDS victim from ten months to twenty months <pause dur="2.1"/> so it had an effect <pause dur="0.5"/> one shouldn't underestimate its effect <pause dur="0.7"/> but <pause dur="0.8"/> it didn't mean that you were going to survive <pause dur="0.9"/> for <pause dur="0.2"/> a long period of time and have a natural lifespan <pause dur="1.4"/> okay i want to talk <pause dur="0.8"/> a little bit about <pause dur="0.4"/> the division of these different <pause dur="0.6"/> # stages of the disease <pause dur="0.8"/> by symptomology <pause dur="1.6"/> and <pause dur="0.3"/> this really <pause dur="2.3"/> deals with the <pause dur="0.3"/> the clinical pattern of disease <pause dur="0.9"/> okay <pause dur="1.3"/> and i want to <pause dur="0.3"/><kinesic desc="indicates slide" iterated="n"/> keep referring back to this as i talk about the clinical pattern of disease <pause dur="0.4"/> okay <pause dur="1.7"/> now of course once <pause dur="0.6"/> people started to diagnose H-I-V it became important <pause dur="0.5"/> to have available to clinicians <pause dur="0.4"/> some sort of definition <pause dur="0.9"/> of what stage of this process <pause dur="0.4"/> a particular patient that might present to them <pause dur="0.5"/> was at <pause dur="0.7"/> okay <pause dur="0.8"/> and <pause dur="0.4"/> two systems grew up <pause dur="0.7"/> quite quickly <pause dur="0.6"/> one was proposed by the C-D-C

the Centre for Disease Control remember the place in Atlanta i said that is the sort of <pause dur="0.3"/> American equivalent of the P-H-L-S <pause dur="1.1"/> okay <pause dur="1.3"/> and the other grew up <pause dur="1.2"/> through <pause dur="0.5"/> a major <pause dur="0.2"/> hospital in the United States in Washington called the Walter Reed Hospital now the Walter Reed Hospital has a very long history of dealing with tropical diseases <pause dur="1.4"/> okay <pause dur="0.9"/> and these two <pause dur="0.8"/> # organizations proposed a staging <pause dur="0.9"/> system <pause dur="0.4"/> to allow clinicians to <pause dur="1.0"/> define when a patient presented to them what stage of disease that patient was in <pause dur="1.5"/> the C-D-C system <pause dur="2.1"/> defined people <pause dur="0.7"/> as being in stage one <pause dur="0.6"/><kinesic desc="writes on board" iterated="y" dur="3"/> through <pause dur="0.2"/> to four <pause dur="1.3"/> and this was romanic one through to romanic four <pause dur="4.2"/> the Walter Reed system <pause dur="0.7"/> allowed you to divide <kinesic desc="writes on board" iterated="y" dur="2"/> people <pause dur="0.3"/> in a stages zero to six <pause dur="6.9"/> now it's important of course <pause dur="0.4"/> when a new disease comes along <pause dur="0.2"/> to have some sort of system of clinically defining the disease <pause dur="0.5"/> why is that <vocal desc="belch" iterated="n"/> important excuse me <pause dur="0.7"/> well it allows you to do surveillance studies that's the

first thing it allows you to do it allows you to actually survey the disease <pause dur="0.8"/> particularly when you've got a disease that you know is going to <pause dur="0.6"/> is going to develop over a long period of time <pause dur="0.9"/> it allows you to survey its development <pause dur="0.5"/> it allows you to do epidemiological studies what is the incidence of infection <pause dur="1.5"/> and of course it will if you've got some sort of therapeutic intervention <trunc>metha</trunc> <trunc>measur</trunc> measure method <pause dur="0.4"/> it will allow you to measure how how good that therapeutic intervention is <pause dur="2.0"/> now these two schemes the C-D-C scheme <pause dur="1.6"/><kinesic desc="writes on board" iterated="y" dur="7"/> and the Walter Reed scheme <pause dur="1.6"/> when they were first proposed <pause dur="1.0"/> in the middle nineteen-eighties they were both used <pause dur="3.1"/> they each have advantages and disadvantages <pause dur="1.8"/> the C-D-C system <pause dur="0.9"/> is largely based on clinical observation of the patient <pause dur="3.0"/> so basic simple clinical observation of the patient <pause dur="1.1"/> weight <pause dur="1.1"/> # symptomology <pause dur="1.1"/> okay <pause dur="0.5"/> very little lab very little involvement of lab indicators

or immune system indicators <pause dur="1.2"/> by contrast the Walter Reed system <pause dur="0.7"/> is <trunc>ba</trunc> is mainly based <pause dur="0.4"/> on laboratory diagnostic assays <pause dur="6.3"/> now on a global scale <pause dur="0.6"/> the C-D-C system <pause dur="0.7"/> took over relatively quickly <pause dur="0.9"/> from the Walter Reed system and the main reason for that <pause dur="0.2"/> was because <pause dur="0.6"/> the disease grew rapidly <pause dur="0.4"/> in countries that were not well set up <pause dur="0.5"/> to do the laboratory diagnostic assays that could easily be done in the United States <pause dur="1.5"/> and so the C-D-C system is the system that you will most often hear about today and is the system that's broadly used <pause dur="0.4"/> to define what stage someone is in <pause dur="3.7"/> so <pause dur="0.3"/> in this system then stage one <pause dur="4.0"/><kinesic desc="writes on board" iterated="y" dur="1"/> is the acute <pause dur="0.4"/> phase of infection <pause dur="6.6"/> and this acute primary infection <pause dur="0.6"/><kinesic desc="indicates point on slide" iterated="n"/> period <pause dur="1.3"/> is most usually asymptomatic <pause dur="2.2"/> so the person is infected <pause dur="1.6"/> but most commonly they have no idea that they are infected they they exhibit no symptomology <pause dur="1.0"/> if they do <trunc>exhibtib</trunc> # exhibit symptomology <pause dur="0.7"/> it's basically a flu-like syndrome <pause dur="2.1"/> they might get some fever they might get a bit of nausea they might

be a little bit lethargic perhaps a little bit of diarrhoea <pause dur="0.4"/> a sore throat et cetera <pause dur="0.8"/> but nothing that's very specific i mean there are lots of things that would cause that <pause dur="0.8"/> you know a bad night on the bevvy would cause most of those symptoms <pause dur="0.3"/> okay so <pause dur="0.6"/> in the acute phase there really # <trunc>ev</trunc> if there's any symptomology at all <pause dur="0.8"/> it's nothing that you can kind of put your finger on and say ah you know i know this person is probably infected with H-I-V because they've got this symptom <pause dur="1.1"/> okay <pause dur="3.1"/> the only lab indicators you get in this acute phase <pause dur="0.3"/> are a transient leukopenia and <trunc>lympha</trunc> <pause dur="0.2"/> lymphopenia <pause dur="1.2"/> so a transient drop <trunc>leukope</trunc> penia <pause dur="0.5"/> means drop basically <pause dur="1.0"/> so a transient drop in leukocyte numbers and lymphocyte numbers <pause dur="5.7"/> you might get an inversion <pause dur="0.9"/> of the ratio of C-D-four to C-D-eight cells in the bloodstream <pause dur="2.7"/> but it's important to realize that at this stage in the <trunc>fect</trunc> infection that is not due to a drop in C-D-four cells it's due actually to an increase in C-D-eight cells <pause dur="6.9"/> okay <pause dur="1.7"/> you may

see some atypical lymphocytes in blood smears but you may not <pause dur="1.7"/> okay <pause dur="0.3"/> so the picture i'm painting then of stage one <pause dur="0.6"/> is somebody who's infected <pause dur="2.1"/> probably has no idea they're infected has no symptomology <pause dur="1.7"/> okay <pause dur="1.4"/> and will take <pause dur="0.5"/> somewhere between <pause dur="1.6"/> a few days <pause dur="1.2"/> and as long as three months <pause dur="1.4"/> to seroconvert <pause dur="2.9"/> now you remember i said to you that when people are diagnosed as being H-I-V positive <pause dur="0.8"/> the main form of diagnosis is seroconversion the production of antibodies against one of the structural proteins of the virus <pause dur="2.1"/> so in the period up to three months <pause dur="0.8"/> after the person has been infected <pause dur="1.5"/> there are probably no indicators either to that individual <pause dur="1.7"/> through symptomology or indeed <pause dur="0.5"/> to the health authorities <pause dur="0.6"/> through some sort of diagnostic assay <pause dur="0.2"/> that they've actually been infected <pause dur="2.8"/> unless <pause dur="0.6"/> the diagnosis is looking specifically for virus <pause dur="1.8"/> the reason for that is as you can see <pause dur="0.5"/><kinesic desc="indicates point on slide" iterated="n"/> from the virus count here in the blue line <pause dur="0.7"/> it is

during this period <pause dur="1.4"/> that virus titres in the bloodstream <pause dur="0.7"/> are probably at their highest level until you get right to the terminal stages of disease <pause dur="3.3"/> okay <pause dur="1.2"/> so what does that tell you about this individual <pause dur="0.8"/> in terms of <pause dur="0.4"/> societal risk </u><pause dur="2.5"/> <u who="sm0613" trans="pause"> they're at their most infectious </u><pause dur="0.3"/> <u who="nm0607" trans="pause"> yeah and </u><pause dur="0.8"/> <u who="sm0613" trans="pause"> they don't know </u><pause dur="0.4"/> <u who="nm0607" trans="pause"> and what does that mean for society </u><pause dur="0.5"/> <u who="sm0613" trans="pause"> that <pause dur="0.2"/> you're going to get a lot of spread </u><pause dur="0.4"/> <u who="nm0607" trans="pause"> exactly <pause dur="1.3"/> it's people in this phase here <pause dur="1.0"/> that as far as society is concerned <pause dur="0.3"/> are the greatest danger to society <pause dur="1.5"/> okay <pause dur="0.9"/> because these people <pause dur="0.9"/> don't know they're ill <pause dur="1.3"/> don't know that they've become infected <pause dur="0.9"/> are probably <trunc>con</trunc> going to continue in the lifestyle that they had <pause dur="0.3"/> prior to getting infected <pause dur="1.0"/> and so are probably going to continue to do <pause dur="0.8"/> the very acts that resulted in

them being infected and so are very much more likely <pause dur="0.5"/> to infect other people and they're particularly likely to infect other people <pause dur="0.4"/> because they have the highest level of virus <pause dur="0.3"/> in their bloodstream so they have the greatest chance <kinesic desc="indicates point on slide" iterated="n"/> at this point <pause dur="0.4"/> of passing on the infection <pause dur="2.5"/> okay <pause dur="5.9"/> as far as seroconversion is concerned okay <pause dur="0.8"/> what is the first antibody you would expect to detect after a seroconversion <pause dur="3.3"/> what are the main classes of antibody that you get in the bloodstream <pause dur="2.5"/> there are three <pause dur="2.9"/> huh </u><pause dur="0.9"/> <u who="sf0614" trans="pause"> <unclear>I-G-G</unclear> </u><pause dur="0.5"/> <u who="nm0607" trans="pause"> I-G-G's one </u><pause dur="0.9"/> <u who="sm0615" trans="pause"> I-G-M </u><pause dur="0.3"/> <u who="nm0607" trans="pause"> I-G-M's two <pause dur="2.6"/> what's the third one </u><pause dur="1.6"/> <u who="sm0616" trans="pause"> I-G-N </u><pause dur="0.5"/> <u who="nm0607" trans="pause"> I-G </u><u who="sm0616" trans="latching"> N </u><u who="nm0607" trans="latching"> okay so which out of these three then <pause dur="0.5"/> are you most likely to detect <pause dur="0.7"/> first <pause dur="1.8"/> after

infection </u><pause dur="0.5"/> <u who="sf0617" trans="pause"> I-G-M </u><u who="sm0618" trans="overlap"> I-G-M </u><pause dur="0.9"/> <u who="nm0607" trans="pause"> are we sure about that </u><pause dur="0.3"/> <u who="sm0618" trans="pause"> <gap reason="inaudible" extent="1 sec"/></u><pause dur="0.9"/> <u who="nm0607" trans="pause"> yeah </u><pause dur="0.5"/> <u who="sf0617" trans="pause"> yeah </u><pause dur="1.5"/> <u who="nm0607" trans="pause"> well you're right what happens with I-G-M remember <pause dur="0.5"/> is I-G-M is the antibody that's initially produced to an infection <pause dur="0.5"/> it rises very rapidly <pause dur="1.0"/> you can often detect an I-G-M response <pause dur="0.3"/> in <pause dur="0.3"/> a few days <pause dur="0.7"/> in the case of H-I-V you may <trunc>un</trunc> <pause dur="0.2"/> you may <trunc>intec</trunc> detect an I-G-M response in as little as five days post-infection <pause dur="0.6"/> if you go looking for it <pause dur="2.2"/> it peaks <pause dur="0.6"/> at about twenty-four days <pause dur="0.3"/> plus or minus seventeen <pause dur="2.4"/> and it disappears it goes back down again remember I-G-M drops away again <pause dur="0.8"/> and it disappears by day eighty-one <pause dur="0.2"/> plus or minus twenty-seven days <pause dur="4.0"/> so <pause dur="0.6"/> if you go looking for I-G-M <pause dur="0.3"/> to H-I-V <pause dur="0.3"/> four months after infection you won't find it right <pause dur="0.5"/> it's gone <pause dur="2.1"/> I-G-G <pause dur="1.7"/> can be <pause dur="0.3"/> most early detected about eleven days <pause dur="0.6"/> so <pause dur="0.4"/> almost two weeks after initial infection <pause dur="1.8"/> it doesn't peak <pause dur="0.7"/> to a hundred-and-thirty-three days plus or minus sixty-three days <pause dur="7.9"/> so it's about three months <pause dur="0.7"/> after the person's infected <pause dur="0.9"/> that I-G-G the stable

long term antibody response that you will see in a human <pause dur="1.4"/> peaks <pause dur="1.3"/> okay <pause dur="1.1"/> so that's all i'm going to going to <sic corr="say">stay</sic> about stage one <pause dur="1.5"/> other than to say that <pause dur="1.7"/> you must <pause dur="0.3"/> notice <pause dur="0.3"/> that what happens at the end of stage one as far as the virus titre is concerned <pause dur="1.0"/> is that it drops <pause dur="2.1"/> and you should remember that this <kinesic desc="indicates point on slide" iterated="n"/> graph over here <pause dur="0.6"/> the virus titre is a log scale <pause dur="1.9"/> so it's a it's <pause dur="0.2"/> it's a little bit misleading to look at this graph and think oh well it doesn't actually go down very much <pause dur="1.9"/> it drops about a hundredfold <pause dur="2.1"/> to a thousandfold in terms of titre <pause dur="0.9"/> that means that at the end of the acute phase <pause dur="0.6"/> the person is going to be <pause dur="0.2"/> a hundred to a thousand times less likely <pause dur="0.7"/> to transmit the virus <pause dur="0.7"/> than they are at the peak of the acute phase <pause dur="2.2"/><kinesic desc="indicates point on slide" iterated="n"/> this drop in virus <pause dur="0.5"/> is as a response of the <trunc>immu</trunc> is is <pause dur="0.8"/> comes from the immune response <pause dur="0.8"/> that has been activated against the virus both a <pause dur="0.3"/> humoral and cell-mediated immune response <pause dur="0.7"/> that is able to some degree to get the virus under

control and eliminate it <pause dur="1.5"/> but the crucial thing is it's to some degree <pause dur="1.7"/> like all persistent virus infections <pause dur="0.4"/> the immune response in this case is not able to completely eliminate the virus <pause dur="2.9"/> it gets it under control but it doesn't eliminate it <pause dur="3.1"/> okay <pause dur="0.4"/> so that takes us from stage one then <pause dur="0.5"/> into stage two <pause dur="2.8"/><kinesic desc="writes on board" iterated="y" dur="1"/> now stage two of infection <pause dur="0.7"/> is this period of what is usually referred to as clinical latency <pause dur="5.8"/> now what you can see in clinical latency <pause dur="1.8"/> is that first of all it can be very long <pause dur="2.1"/> okay <pause dur="1.2"/> it can also be relatively short <pause dur="3.0"/> so of course when it was realized <pause dur="1.2"/> that this period <pause dur="1.1"/> was of variable <pause dur="1.2"/> and somewhat indeterminate length <pause dur="1.1"/> the first thing that people started looking for <pause dur="0.6"/> were prognostic indicators <pause dur="2.0"/> was there any indicator during this period <pause dur="0.7"/> that would tell you how long it's going to last <pause dur="2.8"/> and why would that be important well it would be important because <pause dur="0.4"/> during <kinesic desc="indicates point on slide" iterated="n"/> this period <pause dur="0.5"/> the people are well <pause dur="2.0"/> they're not <trunc>a</trunc> they're not exhibiting any disease symptoms <pause dur="0.3"/> they are

well <pause dur="1.2"/> okay <pause dur="0.8"/> if you acquire the infection <pause dur="0.6"/> at twenty years of age <pause dur="1.0"/> and somebody <sic corr="tells">sells</sic> you well according to your prognostic indicator <pause dur="0.4"/> you're not likely to go out of this <pause dur="0.2"/> period of clinical latency for fifty years <pause dur="0.9"/> you're not going to worry about it too much right 'cause you're probably going to be killed by something else before you get to seventy <pause dur="0.6"/> yeah <pause dur="0.7"/> but if somebody says to you <pause dur="0.4"/> according to your <trunc>prostic</trunc> prognostic indicators your clinical <trunc>peri</trunc> period of clinical latency is going to be two years <pause dur="1.2"/> then you're going to start <pause dur="0.2"/> you know living life and spending money pretty quick because <shift feature="voice" new="laugh"/>in<shift feature="voice" new="normal"/> five years you're going to be dead <pause dur="0.4"/> probably in four years you're going to be dead <pause dur="0.6"/> okay <pause dur="1.5"/> i i've i've laid it out in a in a dramatic fashion <pause dur="0.3"/> so that you realize that there was an enormous amount of pressure in the mid-eighties <pause dur="0.4"/> to try and come up with prognostic indicators because that's what people were worried about <pause dur="1.0"/> i am sick doctor you know <pause dur="0.3"/> i am

infected with something doctor when am i going to get sick is the question that was being asked <pause dur="0.7"/> okay <pause dur="1.9"/> now what you can see that is going on during this period <pause dur="1.1"/> is <pause dur="0.6"/> there is a very slow but almost imperceptible rise <pause dur="0.6"/> in the viral load <pause dur="2.7"/> the level of virus in the bloodstream <pause dur="1.4"/> okay <pause dur="3.4"/> but at the same time there is a clear drop going on <pause dur="1.1"/> in the level of C-D-four-positive lymphocytes <pause dur="1.3"/> in the bloodstream <pause dur="4.8"/> and in fact the <pause dur="0.4"/> the first sort of indicator <pause dur="1.3"/> that people started to use <pause dur="4.3"/> were <pause dur="2.9"/> this level of C-D-four count <pause dur="0.9"/> i should just back up a second and just <pause dur="0.3"/> tell you a little bit about in the in the epidemic in the United States which was the <trunc>e</trunc> area where the long <trunc>ter</trunc> first long term studies were done <pause dur="1.6"/> they started by looking at <pause dur="0.6"/> about seven-thousand homosexuals <pause dur="0.6"/> over a ten year period <pause dur="0.9"/> yeah <pause dur="0.4"/> so the first ten years from the <pause dur="0.7"/> from the <pause dur="0.3"/> early nineteen-eighties through to the early nineteen-nineties <pause dur="0.6"/> and in that ten year period <pause dur="2.3"/> thirty-six per cent of them <pause dur="0.3"/> thirty-six per cent of

the people had developed AIDS within that ten year period <pause dur="4.2"/> forty-four per cent of them <pause dur="1.0"/> were showing symptoms of going into AIDS by the end of the ten year period <pause dur="0.7"/> so these were people who were recruited early they were already infected early in the <pause dur="1.1"/> epidemic <pause dur="0.5"/> and followed over ten years <pause dur="1.4"/> so by the end of that ten years <pause dur="0.5"/> somewhere close to eighty per cent of them <pause dur="0.9"/> were already showing symptoms of going into disease <pause dur="2.7"/> but twenty per cent of them one in five <pause dur="0.4"/> were completely asymptomatic at the end of a ten year period <pause dur="1.0"/> and this is in the period where there was really virtually no <pause dur="1.1"/> # antiviral <trunc>immuno</trunc> # antiviral therapy going on <pause dur="2.0"/> okay <pause dur="3.2"/> now <pause dur="0.3"/> prognostic indicator <pause dur="1.3"/> C-D-four counts <pause dur="3.4"/> people in the early phase <pause dur="1.5"/> of <pause dur="0.7"/> the next stage stage three <pause dur="2.0"/><kinesic desc="writes on board" iterated="y" dur="2"/> now stage three if you look at the recent literature <pause dur="0.4"/> stage three has kind of fallen into disrepute <pause dur="1.2"/> it used to be a period where <pause dur="0.5"/> people were said to have what's called either ARC <pause dur="0.5"/> AIDS Related Complex <pause dur="1.9"/> or P-G-L Progressive

Generalized <sic corr="Lymphadenopathy">Lymphoadenopathy</sic> <pause dur="3.2"/> and in a sense what it was measuring was people starting to <pause dur="0.4"/> tip over into AIDS <pause dur="5.6"/> and <pause dur="0.9"/> one study for example <pause dur="0.6"/> looking at homosexual men who were already in P-G-L <pause dur="0.5"/> so were already at the end of stage two beginning of stage three <pause dur="1.3"/> followed them over twenty months so only two-and-a-half years <pause dur="1.2"/> and if their C-D-four count at the beginning of that twenty months was less than two-hundred <pause dur="1.1"/><kinesic desc="writes on board" iterated="y" dur="2"/> per ml <pause dur="1.9"/> by the end of the twenty month period sixty per cent of them had progressed to AIDS <pause dur="3.7"/> by contrast <pause dur="0.8"/> if their <pause dur="1.5"/><kinesic desc="writes on board" iterated="y" dur="5"/> C-D-four count was greater than three-hundred-and-fifty <pause dur="1.8"/> per ml <pause dur="2.0"/> only ten per cent of them <pause dur="0.7"/> were in full-blown AIDS </u><pause dur="2.3"/> <u who="sm0619" trans="pause"> sorry what was the percentage of the first one </u><u who="nm0607" trans="latching"> sixty <pause dur="0.2"/> sixty per cent of the people after twenty months <pause dur="0.4"/> were in full-blown AIDS if their C-D-four count at the beginning was <kinesic desc="indicates point on board" iterated="n"/> this level <pause dur="1.8"/> and <pause dur="1.0"/> only ten per cent if it was <kinesic desc="indicates point on board" iterated="n"/> this level <pause dur="1.9"/>

it's important to point out to you that in these early studies there was a lot of controversy <pause dur="0.6"/> because people were not used to measuring <pause dur="0.5"/> C-D-four counts in humans <pause dur="0.7"/> and it took a little while to realize that actually your C-D <pause dur="0.2"/> your C-D-four count <pause dur="0.5"/> actually has a daily rhythm <pause dur="0.9"/> it goes up and down each day <pause dur="0.7"/> so of course if you were <trunc>mea</trunc> # <trunc>d</trunc> the count you were getting would depend on when in the day you measured it so there was quite a lot of confusion in the literature <pause dur="0.5"/> 'cause people were quoting different figures because they were measuring the counts at different times of the day <pause dur="1.0"/> okay <pause dur="1.1"/> once that was figured out once the diurnal rhythm <pause dur="0.5"/> of C-D-four counts were was figured out of course they started measuring at the same time each day <pause dur="0.3"/> so they could get comparative data <pause dur="4.4"/> so what about <pause dur="1.1"/> so that's stages <pause dur="0.2"/> one two and three and as i've said to you <pause dur="0.6"/> three <pause dur="0.5"/> has largely fallen into disrepute <pause dur="2.6"/><kinesic desc="writes on board" iterated="y" dur="2"/> that takes us on to stage four <pause dur="2.1"/> stage four <pause dur="1.4"/> is <pause dur="0.4"/> what is now

commonly referred to <pause dur="1.2"/> as full-blown AIDS <pause dur="6.5"/> how do you define the entry into stage four <pause dur="0.8"/> well three main criteria <pause dur="3.1"/> have been used <pause dur="1.3"/> the first is <pause dur="1.1"/> fever for <pause dur="0.3"/> persisting for more than a month <pause dur="6.8"/> involuntary weight loss <pause dur="0.2"/> at greater than ten per cent of baseline <pause dur="2.3"/> so this is not somebody going on a diet and managing to lose one stone in ten <pause dur="0.7"/> because they're on a diet this is somebody losing <pause dur="0.2"/> one stone in ten without trying <pause dur="2.2"/> okay <pause dur="1.5"/> and diarrhoea for more than a month <pause dur="4.1"/> and you've got to have <pause dur="1.6"/> all of these symptoms <pause dur="1.6"/> without any other <pause dur="0.4"/> concurrent reason other than the fact that you're infected with H-I-V <pause dur="3.8"/> so it's not just that you've <pause dur="0.3"/> kept on going to the same Indian restaurant and eaten you know a pretty <pause dur="0.3"/> nasty meal that's been giving you a <pause dur="0.2"/> you know <pause dur="0.8"/> bad diarrhoea for a month and you've not learned you know you'd better change your restaurant i mean it's it's <pause dur="0.4"/> you haven't got any other reason why this is happening to you other than that you're infected with H-I-V <pause dur="4.0"/> okay let's ask

something about then the viral dynamics that are going on during these different phases <pause dur="4.3"/><kinesic desc="changes slide" iterated="n"/> if we look at the virus what's going on in in # <pause dur="0.3"/> the primary infection phase <pause dur="3.4"/> is the virus is growing flat out <pause dur="0.2"/> there's no immune response there of <trunc>a</trunc> of any <trunc>s</trunc> consequence <pause dur="0.5"/> the virus is just growing in a completely unrestricted fashion <pause dur="0.5"/> it has a doubling time of about ten hours <pause dur="1.4"/> peak viraemia will occur at about three weeks <pause dur="1.4"/> and each infected cell is going to <pause dur="0.9"/> seed roughly twenty <pause dur="1.8"/> new cells <pause dur="0.8"/> to become infected <pause dur="2.3"/> but the last sentence is quite important <pause dur="0.4"/> the virus load starts to drop rapidly <pause dur="0.5"/> as the immune response is activated <pause dur="0.8"/> so you should not <pause dur="0.4"/> be under the impression that <pause dur="0.5"/> the immune response that we amount to H-I-V is completely useless <pause dur="0.2"/> it's not <pause dur="1.2"/> it does a pretty good job <pause dur="0.5"/> at controlling the initial acute infection <pause dur="1.6"/> it reduces the viral load between a hundred and a thousandfold <pause dur="1.2"/> okay <pause dur="0.8"/> the only problem is it doesn't completely eliminate the virus <pause dur="2.1"/> during the

asymptomatic phase <pause dur="3.3"/> you have something like ten-to-the-ten virus particles being made every day <pause dur="3.2"/> and you have something like ten-to-the-nine <pause dur="0.4"/> C-D-four-positive lymphocytes <pause dur="0.5"/> being made and eliminated every day <pause dur="1.5"/> so you can see that virus replication <pause dur="1.2"/> and elimination because remember if a C-D-four is cell is eliminated you're going to eliminate the virus that's replicating in that cell <pause dur="1.3"/> you have a rough balance here <pause dur="0.9"/> and this is sometimes referred to as the steady state <pause dur="4.3"/> what that means is that <pause dur="2.0"/> the whole infection <pause dur="0.7"/> is actually being sustained by only about ten-to-the-six to ten-to-the-seven <trunc>ce</trunc> T-cells in the body <pause dur="2.3"/> these are productively infected activated T-cells <pause dur="4.2"/> the <trunc>si</trunc> the size of the latent H-I-V reservoir <pause dur="2.1"/> okay <pause dur="1.1"/> is mostly in resting T-cells <pause dur="0.8"/> and it's about similar in size <pause dur="8.8"/> it's important to point out to you <pause dur="0.2"/> just to remind you <pause dur="0.9"/> that when somebody goes into stage four <pause dur="1.4"/> the immune system loses control of the virus replication again <pause dur="0.8"/> and virus replication takes off <pause dur="2.8"/> and so

in <pause dur="0.4"/> stage four <pause dur="0.5"/> there's again a <trunc>s</trunc> <pause dur="0.2"/> the <trunc>previo</trunc> one of the previous slides showed you <pause dur="0.4"/> a viraemia a strong viraemia <pause dur="1.8"/> okay <pause dur="1.4"/> a lot of virus in the bloodstream <pause dur="1.4"/> a high chance <pause dur="1.0"/> of <pause dur="0.2"/> potential virus spread <pause dur="0.9"/> if <pause dur="1.6"/> the individual was indulging in activities that would be likely to spread the virus <pause dur="2.0"/> but remember there's a big contrast <pause dur="0.7"/> between somebody who's in the acute phase <pause dur="0.5"/> and somebody who's in the symptomatic end phase <pause dur="1.2"/> this is essentially a sexually transmitted disease <pause dur="0.7"/> if you don't know you're infected <pause dur="0.5"/> as will be the case in the acute phase <pause dur="0.6"/> you will be undertaking your normal sexual activity be it <pause dur="0.3"/> you know once a day once a week once a month once a year <pause dur="0.6"/> okay <pause dur="1.0"/> if you're in late stage AIDS <pause dur="1.1"/> you're not interested in sex i mean sex is the last thing you've got on your mind you

know <pause dur="0.4"/> you've got on your mind coping with the symptomology <pause dur="0.4"/> that you're suffering from <pause dur="0.5"/> rapid weight loss <pause dur="0.6"/> you've got diarrhoea you've got fever <pause dur="0.4"/> as i explained to you on the first lecture you might have an <trunc>opportusisti</trunc> <pause dur="0.2"/> opportunistic infection like athlete's foot up to the knee <pause dur="0.4"/> it's <trunc>sym</trunc> in symptom terms <pause dur="0.3"/> it's a very unpleasant # end stage infection <pause dur="0.9"/> and so actually people in full-blown AIDS <pause dur="0.3"/> are not a major risk <pause dur="0.7"/> to society <pause dur="1.3"/> they might be a risk to the people who are actually treating them <pause dur="0.6"/> and the people who are treating them have to be careful <pause dur="0.4"/> that they don't come into contact with blood <pause dur="0.9"/> remember these people may be bleeding from a number of orifices <pause dur="1.0"/> but they they don't pose a large risk to society <pause dur="1.5"/> okay my time's up i'll stop there and continue next <pause dur="0.8"/> Tuesday </u><pause dur="0.2"/> <u who="sf0620" trans="pause"> mm-hmm </u><pause dur="0.2"/> <u who="nm0607" trans="pause"> <trunc>tuesd</trunc> Tuesday i think it is <pause dur="2.5"/> okay