Understanding HIV: Past, Present, and Future - UCSF Mini Medical School

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Heat. Heat. [Music] I'd like to um welcome all of you to the

UCSF U mini medical school. The topic being HIV past um present and future. Um my name is Diane Havler and I am

professor of medicine at UCSF and I run the HIV AIDS program at San Francisco General Hospital. Um I wanted to start

out um with a couple of thank yous. First of all, I want to thank all of you for signing up for this um course. I'd

like to thank UCSF for allowing us to feature HIV in the mini medical school. I'd like to thank our uh technical

folks, Kyle and John, who are at the back of the room. And if I'm waving like this, it's because they're giving me

signals. And I'd also like to give start out by giving a big round of applause to the physician who has organized this

program, who's going to be our first speaker for this evening, Dr. Monica Gandhi. So, a big round of appl applause

for Dr. [Applause] Gandhi. So, we're a little biased in in

in the HIV AIDS field, but AIDS is like no really other story in modern medicine. Um, AIDS HIV is a story of

despair. It's a story of discovery. It's a story of fear. It's a story of courage. It's a story of medical triumph

and a little bit sadly for me to say right now, it's also a story right now of complacency. And I'm really delighted

to see all of you here because HIV AIDS still is a global public health emergency. And there's 34 million people

living with this disease and over two million new infections every year. And somehow it's fallen a little bit off the

public radar screen. But there's so much work to be done. And we here in San Francisco are very unfortunate are very

fortunate to have the cutting edge leaders from all around the world who are you're going to hear about um in

this course. So this evening we have a two-part program. The in the first part of our program we are going to um hear a

lecture on um Monica Gandhi is going to tell us about the origin of HIV and the entry into human populations. This is

something that people always ask, how did HIV start? Where did it come from? And to be honest, there's lots of myths

about that, but our mythbuster Monica Gandhi is going to set the record straight this evening. So, one of the

goals um that we have in our mini medical school course that after you leave this evening, you feel like you

have a firm understanding of really the origin of HIV. So, um our first speaker, as I

said, is Dr. Monica Monica Gandhi. Um Dr. Gandhi is um hails uh from Utah. She went to the University of Utah and then

she went to Harvard Medical School. Um somewhere in between she got a degree in British literature from Cambridge which

we always find very interesting about Monica and fortunately she came over to the west coast where she specialized

infectious disease and then she uh has been a faculty in the HIV AIDS division. Interestingly, her brother also works in

infectious disease and HIV in the other institution, Harvard. Um, but we have Monica here and uh it's it's really a

delight. She is truly one of our premier educators in our program and you'll see why u when you hear her lecture this

evening. So, [Applause] Monica, thank you so much for that

introduction and thank you all so much for being here. I look forward to spending the next six weeks with you. Um

so I want to talk about um where HIV could have entered human populations and when and um we think we have a good idea

of this but um but I think this often generates a lot of questions so I look forward to those at the end. Um so you

know the history of HIV is that one of the first reports of this ever described from Africa was published in kind of a

premier medical journal that I'll be talking about further um in this talk called the Lancet. And at that point um

I want to read you a quote which was that it all started as a rumor. Then we found out we were we were dealing with a

disease. Then we realized that it was an epidemic and now we have accepted it as a tragedy. And that was the chief

epidemiologist in Kala Uganda speaking in 1992. And the description of the disease at the time uh because people

were so wasted from it was called slim disease. The first reports in this country, and

we're going to have a lot more on this history later in the course, but the first reports um of this epidemic that

was called uh AIDS uh were in the what's called the MMWR, one of our um journals um around surveillance in this country.

And these were both published in June and then one followup in July. And these are well known to us. Um we commemorated

uh a couple years ago the 30-year anniversary of these two reports and one described an outbreak of pneumstus

pneumonia among uh gay men in LA and then the second described um in other cities around the country um caposi

saroma another infection associated with advanced AIDS um and these were the first reports in this country and thus

the first um clinical reports um of of this cluster. So I want to take a step back and say okay how do infectious

diseases enter human populations when we talk about HIV? How does this happen with all pathogens? So I'm going to use

the word pathogen um and micro. So microbe being a tiny little organism, a virus, a bacteria, a fungus, a parasite

that comes into human populations. And I'm going to use that word microbe and pathogen um sort of interchangeably. And

most mostly in the world actually because uh organisms have to live microbes are sitting happily in the

organism um and and living very well within that organism. So for instance we have um a number of different organisms

that are incorporated and even into our very fabric of our DNA are all over our body are our our lining our gut and most

microbes live in harmony with their hosts. And in fact there's um well-known examples of commensal relationships.

This is an example of a crab in a coral and they live very happily together and the crab eats the mucus that's secreted

off the coral and all the detritis that comes into the coral and then the crab protects the coral from predators. So

this is an example of a commensal relationship. But what happens is that when coexisting microbes in your body

can evolve and can become more virilent or can start causing hum disease in the human body or a new pathogen from the

environment can come into and enter the human host and these are the two ways that uh emerging diseases occur that a

new disease is observed in human populations and it's actually human I'll put activities in quotes um but human

sort of interference with the environment that can lead to the emergence of new diseases in humans. So

for instance, global warming is a good example that as the earth warms up um microbes that previously could only

exist in one environment can now exist in another environment and then they're exposed to new hosts and can go crazy

with those new hosts. We'll be talking about this second one which is interaction with animals. Um either

hunting or eating or keeping animals as pets. This process by which microbes or pathogens go from a nonhuman to a human

host is called zunosis. And HIV we think is a zunotic uh illness. There's also changes in agricultural patterns. So as

you farm new crops that attracts new pests that can infect a farming community. Um, as we encroach on animal

habitats, animals are crowded more densely together and animals that shouldn't be so close together are very

close together and they can mix u microbes and new microbes can emerge. Um, and also if we go into habitats that

we've never been together, we are exposed to new u microbes. As urbanization occurs, of course um humans

are crowded into small spaces and that's um delightful for uh contagious diseases. And then modern transport of

course that jet travel makes it so that organisms can go in a day from one place on the earth to other uh to the other

even when someone feels quite well um or ships can of course carry unintended passengers in the forms of microbes. And

then of course there's war and famine and all the other human activities that can contribute to disease. So let's talk

about HIV then specifically once we've have a larger framework of how diseases enter populations. HIV itself is a um

type of virus called a lenta virus and that is a subgroup of viruses called retroviruses. So I'll explain what retro

and what lenta is. Retro means that um these viruses use RNA as their genetic material. And eventually that RNA we

have DNA as our genetic material. Um but that RNA eventually has to convert to DNA once this virus enters the human

host to cause more mischief. Lentiva virus that lenta part means slow and that means and this is very clever of

this virus but that means that there's a long interval between the initial infection and the time that someone gets

sick and that long interval is the time in which a person can spread the disease even though they feel quite well. And so

the lenta viruses um are a subclass of retroviruses. And were there ever anything in in in the animal kingdom

that we knew about that uh was comparable to the lenta virus of HIV in human populations? Well indeed there's a

a completely almost analogous um bunch of viruses that live in primates and these are called uh these lentiva

viruses that live in primates just like human immuno deficiency virus spells out HIV these are called Simeon immuno

deficiency viruses SIV strains and there are many many um SIV strains that live very happily with their primate hosts.

So again, I told you that there are many microbes that live happily with their hosts. And it's only when a microbe like

SIV gets away from its host that it's living commensely and fine with to a host that it's not supposed to be in

like humans that disease can occur. So many of these primates um for centuries have lived with their SIV strains and

not um gotten sick. And there are SIV strains found in chimpanzees, gorillas, monkeys, African green monkeys, baboons,

sudi mangabes, Sykes monkeys, u many many primate species. So let's think about first I'm going to tell you about

which strains of SIV most look like our strain of HIV and then we'll speculate on how um that crossover from the

primate to the human occurred. So let's um do a little bit more background about what are the types of

HIV that are found in human populations. It's pretty easy. There are actually just two major types of HIV strains in

the world. HIV1 and HIV 2. It does get a little more complicated because from there there are some groups um of HIV1.

There are four different groups um group M, N, O, and P. And then group M HIV is that pandemic strain. So that is the

strain that causes over 90% of all human infections. HIV1 group M. And group M has a number of different subtypes that

we actually call clades. And just I'll point out there are different clades. There's not an E, but A B C D F G and so

on. And cate B is the strain um that's found in the US. So this map below is kind of small but you can see that B is

the strain that's predominantly found in the US. So when we think about HIV and which strains are homologous to SIV

strains, let's just focus on HIV1 and HIV 2. So it if you just look at and I'm not

talking about how the crossover occurred but if you just look at what strain looks like the other HIV1 the major SIV

strain that closely most closely resembles SIV uh most closely resembles HIV1 is the particular SIV strain found

in the common chimpanzeee and this um subspecies is called pant troades trogodities and there's an example in

the San Francisco zoo and poor guy he's all by himself um but He often sits up on a tree and he um I have to go to the

zoo a lot because I have these children. Um but but he this is this SIV strain looks like if you sequence it, if you

actually look in a laboratory and look at what it looks like, it looks most like HIV1, the one in the common

chimpanzeee. HIV2, its SIV strain that it most closely looks like is an SIV strain found in Sudi mangabes. And this

illustration is from a really nice paper and I've included the um papers if you want more information down at the

bottom. Um but this illustration shows a group of researchers that went to East Cameroon and they would collect fecal

samples from all the different primate species that lived in East Cameroon and they could see which SIV strain from

these samples looked most like HIV1. So it's actually quite simple then. So HIV1, group N, M, and O all look most

like the SIV from the common chimpanzeee. Group P, and this is a very rare strain and was first reported out

of Europe, but it was an immigrant from West Africa. Um, group P actually is a is a strain that most looks like an SIV

uh that is found in gorillas. And then HIV2, as I told you, looks most like um the SIV strain from Sudi mangabes. So

that just tells you what the strains look like. That doesn't tell you how this jump was made from primate to

human. So how did we get the viruses from these primates, these SIV viruses that are living in these primates? How

did they jump into human populations? Well, one of the first theories that was um propounded on this

was um published um in u by a um journalist named Edward Hooper. And this publication was called the river, a

journey to the source of HIV AIDS. And the backstory here was that um in the late 50s there was a competition for the

um vaccines that were going to be used um globally. So there was the oral vaccine that had been designed uh by

Sabin um and then there was a um injectable vaccine that was designed by SulkQ. And um there was a Polish

scientist named Hillary Kapowski who was actually competing with Sabin for the development of the first oral polio

vaccine. And the National Institutes of Health in the late 50s held a special committee to say okay which one's more

effective which one's the most safe and Sabin won out as the developer of the oral vaccine. Um but Krowski um who was

in um affiliated with Belgium at the time um went on um despite this recommendation to administer his vaccine

to a million people in um in uh territories that were controlled by Belgium at the time. So um at the time

this was called the Belgian Congo now called the Democratic Republic of Congo, Rwanda and Burundi. And so a hund

million or more of these oral vaccines were given. And um the theory was and this theory was uh propounded by Edward

Hooper and then actually published um uh by the Rolling Stone which gave it um the magazine which gave it some

popularity um was that Kapowski was responsible for this. Um the I'm sorry that these slides are cut off. A lot of

them are. But um there was a lot of reasons why this theory didn't actually hold up. Um, one is that the culture

median that Kapowski used to make these oral vaccines actually were not um in um cells from chimpanzees. And we again

know that HIV1M is most closely related to chimpanzeee cells. They were um using African green kidney monkey cells. Two,

and I'm going to talk about that the timing didn't fit of 1957 uh to 1960 was the time that he was

administering these vaccines. didn't fit for later on when when we think that HIV entered human populations. So, Kapowski

sued Rolling Stones for defamation and he got a dollar in um damages. So, what was that crossover

event? And I would make a request um that these slides are cut off by the way they're formatted, but if you guys are

okay with it, I'm just going to proceed. Um but there are going to be a lot of cut offs here. But what was the what was

the crossover event? You know, the most common prevailing theory, and I'm going to give a little bit more evidence about

this, is that um is that um the possibility of crossover was frequent contact between humans and non-human

primates that really occurred um at the beginning of the 20th century, sort of late in the 19th century, and that was

through the medium of the bushmeat trade. Um the wish trade actually refers to hunting wildlife uh not just primates

um for food um or for exotic purposes um but a lot of the focus has been on the hunting of um primates and um a lot of

this theory came I'll refer you to a popular author and a scientist named Nathan Wolf who looked at um uh these

hunters um and all the h all the SIV strains that they're exposed to. So if you take one of these push meat hunters

and look at their DNA, it's actually littered with all these SIV strains that they probably were exposed to from

different primates um that they were hunting um from the blood exposure to those primates. And so that was the

crossover event and the spread was probably something to do as I'm going to talk about more with social disruption,

colonization, the sex trade and history. Um, so this is an example of a nice article that summarizes the bush meat

market and um, this unappetizing um, look at the bush meat market in West and Central Africa with again not just

primates. And um, the reason that this trade grew up so much more uh, at the turn of the century was really access to

modern firearms. There were logging rows that that were created between forests and cities. And um, really at this point

the extinction of some primates are really threatened. And this is an example of um Nathan

Wolf's work that I um indicated to you before, but this is for example um the percentage of HIV positive persons. This

is a paper in rural villages in Cameroon who report contact with wild animals as represented by the dark lines here. And

contact with non-human primates is represented by the whiter bars. And you can see that a very high proportion of

um people um eat wild species or eat um non-human primates. A large proportion up to 80% um butcher um wild species or

butcher um non-human primates. Up to 60% hunt. And then also there's some keeping of um non-human primates as

pets. And this is a little bit technical and there's no reason to understand this fully. I want to just get give you the

gist of this is that if you look at the same 14 rural villages in Cameroon, HIV infected people in those

villages not only have the common strain that spread from human to human um in that region, but they're also have again

in their um in their genomes or in their very fabric of their DNA, which um HIV we know likes to knit itself into our

DNA and we'll talk about that um more um in a weeks when we talk about therapies. Um, HIV these these villagers who are

exposed to non-human primates at such a high rate not only have a predominant strain but have many many many other

strains that resemble SIV strains in different non-human primates including some that we've never even identified.

Um, so the message is really that HIV genetic diversity is common place in villages with frequent contact with

non-human primates. And this is at this point at this point the prevailing theory of how HIV um crossed over. So

the next question then becomes when did HIV cross over? When did it get to human populations? And I told you that the

first description in the United States was in the uh MMWR on June 5th 1981. Um there hadn't been previous reports from

the region of origin. And if we think the region of origin is namely uh specifically West Africa, there had not

been previous to 1981 outbreaks of diseases that we usually um think are associated with having advanced imino

deficiency. But this is difficult to describe in an area where there may be a number of other competing diseases and

tropical diseases and and a number of other outbreaks of other things. Um and so that may not be um the focus. There

was a case report um that created quite a bit of controversy um that was published in again one of these um big

medical journals called the Lancet in 1959 of a 25-year-old man in uh the UK who was a naval seaman um and he came in

severely emaciated. They use these sorts of terms in 1959. So remorseless uh anal lesion um an ulcer eating into the his

upper lip which is illustrated here and the post-mortem in 1959. This case report revealed in his lungs pumacystus

um and cytogallo virus two uh a virus and a fungi that are uh um that are associated with um HIV or advanced

immuno deficiency and later in 1983 the pathologists from the Manchester Royal Infirmary um took his specimens because

he had postmortems available and claimed that they were positive on on what's called plymer's chain reaction for HIV

and that created a lot of controversy um because uh they didn't report their methods well and um and they wouldn't

release any of his specimens for anyone to verify that. So that's still um very very debatable and Edward Hooper, the

same writer who gave us the river did call publicly for an apology to the family and his fiance um for this

report. So, a lot of these are cut off, but um I but I want to um I want to to to go to the next um idea of where we

got this idea of when HIV could have entered human populations. Well, the only way to truly know is to have in

time human specimens. So, if we had um uh human specimens from West Africa from the 1800s, then we could understand if

HIV had been present in human populations in the 1800s. But there are no human specimens. They're not plasma

specimens. They're not lymph node specimens. They're not tissue samples sitting around from which you can

identify HIV that go back very far. Um, some of the oldest known stored specimens from Africa uh were 1,200

plasma specimens that were stored at the University of Washington in Seattle that had been collected in 1959

um from uh what was uh then called the Belgian Congo, now called of course the Democratic Republic of Congo in the city

of Kenshasa. um Leopoldville at the time. And uh these specimens have been collected for an entirely different

purpose. They had been collected for um uh to look at the relationship um between um something called G6P

deficiency and the development of malaria. But they went back to those specimens collected in 1959 and analyzed

all of 1213 for HIV. And HIV was found in one patient in 1959. And this ZIR 59 strain that it was thus called was

intensively studied. And um uh and essentially the way that they could study the Zyr 59 strain is a couple of

ways. They could look at it, sequence it and say how much it differed from the chimpanzeee SIV strain which we think

HIV1 came from. And then also you could look at ZR ZR59 and say how much did it differ from the modern HIV strains that

were in human populations at the time of this um paper which was in the year 2000. A and you you can see by the

illustration that Zyra 59 is there and it closely resembled some of the strains that we find at clades that we find in

human populations BDNF and they did these kind of complex what's called phoggenetic analysis and said you know

Zyra 59 is so close to BDNF it probably could not have entered human populations much uh much before this 1959 and so the

estimated date at this point as of 2000 when this paper was published in your slides the full slide will be published.

Um, at this point we thought HIV entered human populations around 1930 and then another specimen was found

because again that's really the only way to know when HIV was in human populations and a lymph node was found

from an adult female who had um lymphoma in Kenshasa um and it was embedded in paraffin and this was found from 1960

and this strain she she had HIV and this strain was called DRC60. So they thought okay DRC60 is

going to look a lot like Zy 59 because SIV crossed over into humans around 1930. This is now 1960. It had about 30

years um to evolve in the human host. So it shouldn't look too they shouldn't look too different from each other. And

then 1960 to the year 2008 which is when DRC60 was found. Um we know that evolution occurs at a certain um rate in

the human host. So we thought that that this would just verify the hypothesis, but in fact DRC60 actually looked a lot

different than Zy 59 and they were different enough that it looked like there was probably probably a longer

time for HIV to be evolving and growing and mutating in the human host. And so the estimate from this new sample that

was found is that it looked like the ancestor of HIV1M crossed into human populations probably around the turn of

the 20th century. Anywhere between 1884 and 1924 is their estimate and 1908 was their median. So that's when they think

uh by this latest data that HIV entered human populations and then everything that occurred from there was history was

West African history was the history of colonization and of social disruption of what um western countries did in in West

Africa um that disrupted West Africa so uh much to create um uh the growth of this disease. So if we think that HIV

entered around the turn of the century, if you look at now a map of Western Africa at the time, there was no city in

the region, no city in the region at the time that had a population before 1910 of greater than 10,000 people. enter

colonization, enter Belgium, enter um all that was happening in the setting of uh colonialism, including um this uh

establishment of the sex trade and um and and creation of larger cities and uh and um and cities in which um trade was

occurring. And so at that point um once uh colonization uh colonialism occurred in Africa cities became larger and by

the second half of the uh of the n of the 20th century you can see that populations were growing in size and by

about 1960 kinshasa had reached uh greater than 100,000 in population. So the idea here was that it's possible

that HIV was percolating in human populations around the turn of the century and the first half of the 20th

century relatively undetected. There were people were far apart. Uh there was not big cities. There was not people

crowded together. And importantly there wasn't a sex trade uh that was established by um uh by colonists who uh

came and established this. And so um and so probably what happened was it was the super imposition of that history on top

of a low-grade percolating um uh virus in the community that led to the spread of

HIV. And uh I will refer you to this article because it's a nice article if you want to sort of understand all of

this. Um this was published again in the Lancet in 2011. But um if you look at the chimpanzeee on the right again we

think that the pant trogodities trogloid strain passed over into human populations in the 1900s um the gorilla

strain um which was a group P probably passed over in the 1920s um the sudi mangabe strain probably passed over in

the 1930s and then evolution occurred within the human host as it spread within human populations and then all

you have to do is then look at western African history and then go to eastern African and southern African history um

to understand uh what happened from there. I do want to bring up one tiny point um because I don't want to dwell

on this. This is uh this is provocative. Um but I do want to refer you to an interesting paper um that Dr. Havler

actually sent my way in December. It was just published in December 2012. Um but this this was a study which looked at

needs to be replicated. uh only group that's ever looked at this but looked at specifically the Byaka western pygmies

in West Africa. Um and this particular population is exposed most to this common chimpanzeee and specifically that

that that chimpanzeee uh the pan uh trogodolates trudes um that uh has the SIV strain most closely related to our

HIV strain and when they looked at the genome or the genetic structure of this particular subop bya western pygmies

they had evolved genes within the human genome that were protective against HIV. um

they had genes in their genome that are only seen in for instance u um western European populations that were possibly

evolved protection from HIV of HIV uh as a happy accident to evolving protection from smallpox. They had genes in their

genome that we not would not have expected in Western Africa, but they were all associated with being protected

from HIV infection. And this is I'm going to leave you with that. The their ideas that HIV am may have crossed over

into human populations, at least human populations with a lot of exposure to this particular primate a long time ago

and may have even led to changes in the human genome in this particularly isolated population. Leave you with

that. So um so let's go back to history. So what happened from western Africa. So um if I if we think that um that I told

you the kinshas started uh essentially burgeoned in around 1960 to a large population size. There was still long

distances between cities in western Africa, difficulty in travel. Um there was insecurity and violence at the time

um as as as colonialism was being fought and um but what needed to happen for this virus to spread successfully was

that it was carried from western to eastern Africa probably in the 70s and at that point the spread was rapid. Um

if you look at for instance the five countries that border Lake Victoria in East Africa, Uganda, Rwanda, Burundi,

Tanzan Tanzania and Kenya um we know by the mid 80s that the epidemic had reached um really uh frightening

proportions uh already um by the mid 80s at that at at in in those countries. So um there were lots of factors that led

to this. There was labor migration and by 1988 35% of truck drivers in Uganda were positive for HIV. There's a high

ratio of men in the urban centers in East Africa in these countries at the time. Um there was a relatively low

status of women. Circumcision seems to be uh protective and there were low rates of circumcision in the region.

There was a high rate of sex trade and the sexually transmitted infections and um uh by 1986 85% of sex workers in

Nairobi were infected with the virus. And then the virus had to just travel down to South Africa by the Tanzan road.

And by the mid and late 80s um subs Africa and South Africa um was really the focus of this pandemic. And I'm

going to show you a series of maps and then we're going to end um that that illustrate this um this this incredible

spread and this devastation. But this is the map from UN AIDS from 1985 where you can see the darker areas are showing

regions of high prevalence of HIV infection. So again, western and central Africa predominate. By uh 1995, we have

spread all over Africa, very um deep red areas in South Africa, subsaran Africa, and over in Southeast Asia. And then

this is 2005. Um really concentrated uh epidemics in subsaran Africa, spread to um uh the former Soviet Union u and

darker areas as you can see in South Asia um and over to the United States. And this is a um uh again from that same

article that I refer you to if you're interested in really exploring how each particular strain went from place to

place to place. But just to focus in on the United States, we think that um this clay be that's the most predominant

strain in the United States was introduced um from Haiti around 1972. And that's the circled area

there. And this is the current map that will come up again and again. um uh in throughout our course HIV past, present

and future because this is the total number of adults and children estimated to be living with HIV as of the end of

2011. 34.22 million people infected. And as Diane already told you, um 34 uh.2 million infected, but 2 million new

infections. Um I just want to present a teaser for what's going to be coming up in a couple of weeks when we focus on

HIV infection in women and children. But um if you look at the purple line here that represents the percentage of adults

uh worldwide who are living with HIV who are female and you can see the purple line globally the 50% mark was reached

um quite a number of years ago and we're now in 2010 uh you know definitely at a pandemic that affects men and women

equally and in fact in regions of the world where the epidemic is most concentrated like subsaran Africa which

is the green line um you can see that the epidemic is most pronounced in um women. In fact, with o up to almost 60%

of women being infected, 40% of men in densely affected regions. And one comment on children,

but we're going to go over this a lot more, but at this point, Africa has 15 millions AIDS orphans. And um and this

is defined as children who have lost one or more parents to AIDS. And um I do want to point out that there's a

character in the Sesame Street in South Africa who's designed he's tami is actually both an AIDS orphan and HIV

infected himself and um and he is literally present in the in the um South Africa takalini sesame which is the

Sesame Street equivalent to teach children about HIV. And when commi tried to come over to the United States, the

US Traditional Values Coalition in the Senate um said that that would he would encourage homosexuality, but I don't

think he's gay. I think he's just a little kid. Um so, stop AIDS, make the promise. So, thank you so much. And I'll

take questions now on the origin or when it entered human populations and then we'll move to our

panel. and please introduce yourself if you're okay with that when you ask a question. So the spread of the question

was that the spread of HIV did it start from the 1970s. So um the theory is that it entered human populations way before

that probably around um the early uh 1900s but that in 1970s is when cities and so that that HIV was probably

sitting there in human populations at a low rate in West Africa and central Africa um without causing major

outbreaks. Um it was really the the theory of history superimposed on top of the crossover is that it was when cities

developed that were large and concentrated in the setting of urbanization in the setting of social

disruption that occurred with colonization and in the setting of a an of the establishment of a sex trade

where HIV could be spread sexually that HIV started to spread more quickly and that at least in history um if you look

at Western Africa Africa and specifically at the Belgian Congo at the time, what it was called. Um, uh, that

mainly occurred in the 60s and the 70s. And then, as I showed you, as cities became bigger and as these sex trades

grew, it seemed like the spread again, the manifestation of the disease um, was more obvious in the in in the later

decades, 80s and 90s. But no, we think that HIV probably started and came into humans earlier, but it was it required a

certain population density to manifest. Yes. Sorry, I should have Yes. Yes. I should have explained this

better. What this means, what this is indicating of all HIV infected people in a

country, the percentage who are female seem to be 57% and the percentage are male in that region would be 43%. So of

that 30% who are actually infected, this is the breakdown by sex. So not of the entire population. Right. Right. But but

of the HIV infection. Now in this country, we're at about um and again this is this is limited by our

surveillance in this country. Um but in this country right now of all the people who are infected in the United States,

there's about 26% of them are female. So it really depends on the setting. So um I quoted you from 1986 that 85% of sex

workers in Nairobi were infected but there have been major um strides in prevention uh in in sex workers in a

number of different uh countries in Africa and and there have been great strides in India for example. So those

overall percentages have come down. Um, if anyone has an exact percentage in Nairobi at this point among sex workers,

I'd welcome input from any of the faculty, but I don't know where we are right now, but it it couldn't have

gotten worse than 85% and with prevention efforts, it's probably much better than that. And one important uh

point about that is is there are regions where there's what's called generalized epidemics and what's called concentrated

epidemics. So there are places in the world where we think HIV just seems to be in specific high-risisk groups. But

um in countries that are hardest hit, we call them generalized epidemics because the HIV rate may be higher in groups

that are at more risk like sex workers, but the HIV is spread to the general population and that's called a

generalized epidemic. and we can talk more about that after the So that is a great question and will be covered more

the last day of the course um when Peter Hunt talks about immunology of HIV and Jay Levy will probably approach this a

little bit next week. There are a number of reasons why some people um tend to progre take a longer time to to progress

to get sick and there are some people who can even control their their own virus and you're right it has to do with

their own immunity and their own host ability to do that and there's more details on that to come and I I would

refer you to those talks. Yeah, this is a great question. So the question is um uh I hope he everyone heard the question

because I want to explain it a little bit. So um in populations that are highly exposed like a bushmeat hunter

population they actually have probably multiple crossover events. So multiple strains because they have the bloodto

blood exposure. You're absolutely right. They are have cuts on their hands. They're um using uh knives. They're

exposed to the blood products as they uh butcher the animals. So there is absolutely blood to blood exposure like

you said and they can have host a number of different HIV strains but in the general population it's the strain

that's most efficiently transmitted from human to human that goes crazy that gets spread across the world and so somehow

HIV group M you know HIV1 group M is most efficiently transferred otherwise we'd have the gorilla strain everywhere

which is group P we'd have the N strain which is very rare everywhere the O strain So there's something about the M

strain and and there's different reasons for it that it just most efficiently transferred it spread from human to

human. So this is a great question and this is also around um sort of the life cycle

and the mechanism of HIV infection which will be most revealed when um we talk about treatment of HIV because to talk

about treatment of HIV and George Batty will be doing so we're going to talk about the life cycle of the virus and

you're absolutely right the virus enters and uncotates and makes itself into DNA and then eventually integrates into the

human uh chromosome but this aspect that you said that how can you get it out of the chromosome that question what you're

referring to the possibility of cure. He's going to be um is going to be talked about in the last day of the

course. So I would really encourage you to come and hear Steve De's dynamic talk. So I can't cover that that all

here. Um but there's he he's going to do a great job talking about the immunology and and and the possibility of

cure. Any other um and then I think we'll just take uh uh just two more. Okay. Right here please. Yeah. No, it's

an it's an excellent question and uh you know to give the most simplistic example, there's a um uh um they are

resistant partially to HIV because they have mutations in um a gate called the CCR5 receptor that allows HIV to enter

human cells. And if you have mutations in that gate or better yet, you don't make that gate at all, you can be

exposed to HIV as much as you want and you'll never get infected. And so that experiment that you're proposing to

bring that mutational gate into other humans to help them resist HIV infection is the very topic again of the last uh

day of the course where we're going to talk about cure and we're going to talk about those very ideas. So it's an

excellent thought to hold that question. Yeah, that's a really good question about natural hosts being getting sick

when exposed uh when they're infected with SIV because um for instance the macak is not supposed to have um the SIV

pseudangabe strain in it and so the actual model that we use in the laboratory the primate model for HIV2

infection is we've taken the SIV SMU put it in Macs and then uh the macak gets sick and that's the primate model but we

used to think that SIVs didn't make their primates sick. And there's some very very recent data that that may that

may not be true. Um and this was specifically in the um gorilla model, not model, but the gorilla um and it was

the SIV gorilla strain that if present in gorillas seem to sicken the gorillas more than um gorillas that don't have

that SIV strain. So the lenta virus is so slow that it's possible that it is actually affecting ultimately its own

primate, but there's so many competing diseases and so many competing illnesses that it may have been that other things

got to the primate before that occurred. And I'll definitely send you that reference if you um email me. I'm on the

global server and I'll send you that reference. Um that's true of HIV as well. It's in low level in human

populations. If and and in places where there are a lot of tropical diseases, you could be getting sick from other

things and dying from other things before HIV had a chance to make you sick. Um I think we should stop because

uh we have a very exciting panel. So I'm going to um allow Diane to come here. So thank you so much. I'm sorry about these

slides being kind of messed up, but I will email you these slides, the updated slides um later this week. Thank you.

So, thank you Monica for that terrific talk and thanks to the audience. Those were really excellent um questions. A

lot of them are going to be addressed um during the the course. So, now we're going to talk about the the history of

the AIDS epidemic. And I I don't think any community is ever quite ready for an epidemic. And that was certainly the

case in San Francisco in the neur the early 1980s when um HIV uh appeared apparently precipitously. Um I think the

city was on the the the heels of the the the Harvey Mil assassination and the George Mosone. Um there was a lot of uh

bursts of sexual freedom and there was a whole confluence of events that happened um that allowed HIV really to just um

erupt particularly in the MSM community in our city. Um I would refer you in terms of the early years of the HIV

epidemic to a book which is called And the Band Played On by Randy Schultz. Um, in fact, I was thinking at the end of

the course, always got extra copies of this. Maybe we'll raffle off a copy for those of you who make it to the end of

the course. It's really great reading and it goes into the very um early days of the HIV epidemic, particularly Los

Angeles, New York, and San Francisco. Um, on our uh uh curriculum, um we had Dr. Dr. Paul Vulbering who is featured

heavily in the band played on as a speaker for the second uh part of our mini medical school this evening. Um Dr.

Vuling sends his regrets and he was unfortunately unable to attend um this evening. However, in his place and I

hope you will not be disappointed. um we were all thinking well what is the best way for us to convey the history of the

HIV epidemic here in our own city and that's by asking people to talk about who we're here and who were experiencing

um the epidemic. So what we have done is we're going now to move to a panel discussion and I'd like to invite the

panelists to come up to the table and for this segment of the course um what we'll do is I'll ask the um panelists a

couple of questions and then um uh Dr. here is going to give us a brief overview of the

epidemiology currently in San Francisco and then we will open it up to a um panel discussion. So I am going to let

the panelists really share with you their story um and they will uh individually be introduced um as I ask

them questions as opposed to going through a lengthy introduction. So um I'm going to start um with asking a

question to our um first panelist Mr. um uh Lou uh Groso. One of the things that we do in medical school and in medical

education is we invite um patients to talk about their disease and their disease experience. And I have

colleagues who work in various different fields and they say, you know, how did you guys make so much progress in AIDS

and how did things go so quickly? And frankly, it's never been quickly enough for us. But I can tell you the key

secret ingredient is the community. And we in San Francisco have had a community of people affected with this disease. We

would never have made as much progress that we've made. and one of the individuals who really to me is

emblematic of giving their time talking to people about HIV, being a a really true crusader is Mr. um Lucroso. And I'd

like everyone really to give Lou a round of applause for joining with us this evening.

So, I thought we could start out by um asking Lou um just to share his story um about what happened um in the early

years of the HIV epidemic for Lou. Thank you. Um well, in I guess my story

started um I was born in No. Um, in

1986 I came back from a 2 and a half year stent in Germany. And while I was there,

um, I found out that the last person I had had sex with before going to leaving for Germany, so that would have been

June 1983, had died of AIDS while I was in Germany. He got sick and died. Of

course, I didn't know he had it. So I the first day I got I arrived back

home in San Francisco on January 1st and I had an appointment with my doctor on January

3rd and I was tested and kid came back that I was uh HIV positive and he sent me to a doctor who

was then the so-c calledled called expert um Dr. Robert Armstrong I think it was

his name. He was down in Loscatoos and um uh he determined that my tea cells

were really low. they were like around 200 or so and therefore by definition I had AIDS and that I probably had three

years to live and that there was really nothing much I could do just stay healthy, be safe, come in for

checkups. [Music] Um so of course being young um kind of

said yeah okay and went on with the rest of my life and um what I did experience uh one real

issue which I hadn't told anybody about. Um, I had a dentist appointment in late 1986 and um, I went into my my dentist

who I'd known a long time and I told him I had AIDS and he had a real hissy fit and threw me out of the hospital of his

office. I mean, literally yelling, screaming and just threw me out. And that was just yeah, well, okay, I

guess I can't be open about my HIV status anymore.

Um, so much for medical community helping you out, but [Music]

um after after that experience, um I tried keeping it all to myself, um as much as

I could. Um, didn't really tell anybody. Didn't go out. Um, 1989 came and well, I'm supposed to die, so I better get on

with the rest of my life. And I started uh I moved to San Francisco. Moved in with a couple.

[Music] Um, got a new job in a new industry. I became an office manager at a law

bookstore of all things. I was my profession before this was fasten your seat belts. I was in

bowling. I was a bowling center manager, a bowling center mechanic. I taught

bowling. I Yeah. Anything to do with bowling. So I moved to the city and got a job as an office manager at a law

bookstore and um start a new beginning because my life was supposed to end. So new beginnings.

Then um the partner my roommate um started getting sick. I found out he had HIV

um which but he wasn't sick with AIDS. Um, and he started having problems and I

helped him with legal issues and I started taking him to doctor's appointments and we became

close and uh, he got real sick in 1993. um November 3rd, I remember I took him to San Francisco

General and they did a bunch of tests and um they came back and said that he had cancer and probably had about six

months, but they really weren't sure. Their test was showing cancer, but they weren't couldn't be more specific on

that. So they admitted him to the hospital and six weeks later he was in the hospital for six weeks and he they

came back and said to him, um, we know you're sick. We know you've got cancer. We can't locate it. We don't know where

it is. Um, so we're going to say you have AIDS.

It was the the you just fell through the all the slots and the we can't figure it out so you must have AIDS. And they sent

us over to Ward 86 at San Francisco General the outpatient clinic and got in touch with the terrific doctor, Dr.

Donald Abrams and um who was also he was an AIDS doctor and an oncologist and we got

it all figured out and he did have cancer. He had Dan had KS in his colon and no markings of KS anywhere on

his body. It was all in his colon. And um uh I fell in love with with um Donald Abrams and he became my doctor

too. And um uh Dan died in June and um June of 94. and uh Donald and I I was his

patient for many many years until 2004 and that's when I met Brad and Brad became my doctor.

Um, and when I I was exposed to HIV, like I it could have been as early as 1979 or as late as that

June 1983 date. Um, uh, my the medicine I took um, at one point in 1989, I started taking

ACT. it. I didn't have any problems with the meds at all. I It didn't affect me. I didn't get sick from them. There was

no side effects. Um it did nothing for me as far as my numbers stayed the same. Um in

1998 I think it was I got started uh the um uh the new drugs. Um my tea cells went up a little

bit. They went from 200 to 300. Um I feel like I'm one of those people that

um there's something keeping me alive. I don't know what it is. Um, but something's doing it and uh I that's why

I participate in as many studies as I can um as often as I can because I want them

to figure out what's keeping me alive. So um that's about it. Great. Thank you.

[Applause] So our next panelist is um Dion Jones who is a nurse who was raised in France

um did Peace Corps in Togo and then made her way to San Francisco and she's going to tell us how actually she got that job

and uh what she's been doing since. But Dion, what I'd like you to do is to to to share with the with the the students,

um what it was like as a provider in the very very early days of the HIV epidemic, particularly in San Francisco

General Hospital. Okay. Thank you. Um I have some uh sister nurses out there and probably brother nurses, too. Um so, um

thanks a lot, Lou. Um, uh, Mark leaned over and said, "You dumped Donald Abrams for a younger man."

I'm so disappointed, Liv. So, um, so going back to uh, Monica's story and her timeline. So, think back

like, you know, early 1980s in San Francisco. And um in preparation for this uh panel yesterday, I got I uh

watched this new documentary that's called How to Survive a Plague, which is uh nominated for the Academy Awards in

the documentary section. And it's um really about the history of ACTUP primarily on the East Coast uh in New

York. Uh and uh it's an really interesting film for people who are interested in the history of HIV. some

very uh incredible and moving uh uh archival footage. Um, and I think that what it reminded me

of is that um, every community around the world has its story about HIV. And we have our story here in San Francisco.

And we've hosted at San Francisco General many visitors from all over the world that we've collaborated with on

research projects and um, and and travel back and forth. And they always I always ask them I I tend to be the person to

have to do the um uh who are our patients and why is our HIV epidemic so different here in San Francisco than it

is in Tanzania or South Africa or China or Japan. And every place has its story of how this epidemic evolved. in our

story really in the 1980s um started with with this epidemic and this virus really um uh locating itself and finding

a host within the gay community through in the United States in the major urban centers going back to Monica's point

particularly Los Angeles, San Francisco and New York and for those of you that are old enough to remember this was an

incredibly vibrant time in the gay rights movement coming after 30 years of a really growing and maturing civil

rights movement that started uh in the African-American community in the 1950s and then got picked up in the women's

rights movement and then its natural progression was it came upon the lesbians and gay men fighting for civil

rights. It was a straightup civil rights movement and in San Francisco we had a very mature it was a

very political city since since a long time and we had a very mature gay rights movement with institutions and as Diane

referenced we had elected uh our first openly gay elected official Harvey Mil. We had been through the tragedy of his

assassination and that of the mayor of our city. Um and uh it was a mature movement and um with a lot of people

coming from all over the world and all over the United States. In fact, in the early 1980s, the estimate of the number

of gay men living in San Francisco was close to 200,000 people. And then you have this uh this HIV virus. It's a

sexually transmitted disease. And um and just like the women's movement really took up the issue of women's rights and

the issue also of control over our sexuality, the issue of in the lesbian gay rights movement was taking up the

issue of sexuality and the right to have sex. And so here you have a sexually transmitted disease and this virus that

is ha entering in our city at a time when people are having a lot of sex and um and so very quickly it emerged these

patients these people were arriving very sick who had previously been well. They were very young for the most part and uh

our institutions our health institutions were really overrun. So I started working at San Francisco General in

1982. I just graduated from nursing school at City College and um and I was assigned to a medicine ward and um I

would say close to a third of the 34 patients were people living with living with AIDS and dying of AIDS. So back in

those days HIV disease was uh a combination of uh ex caring for extremely ill patients sort of intensive

care nursing and also caring for people who are dying. And so you had this two things that you were holding at the same

time of trying to keep people alive who are extremely sick and at the same time caring for people as they're dying and

really learning how to do that with a population where you're not expecting to be having to do end of life care with a

21-year-old or a 22y old who just found out three months ago that they had this thing called AIDS which back in those

days we didn't even know what caused it. So by 1982 we knew we we knew what AIDS was. AIDS was defined. We weren't

calling it gay related immune deficiency anymore. We knew most likely that it was a sexually transmitted disease and also

bloodborne meaning we had to protect our blood supply and we had to understand how drug use was facilitating

um the transmission of this virus. But we still didn't know what caused it. And um in the city really, and this

is one of the wonderful things about this uh documentary, the how to survive a plague is that at that point in time,

you had these major building blocks of a city. So you needed the science and you needed the medicine and you needed the

policy people and particularly the public health policy people and you needed the politicians, you needed the

health care workers and most importantly what we had as Diane referred to is really what we had was this community of

activists some of whom were infected, many who were not, who were at the table demanding that the services be provided

and that we figure out how to do this, how to do it right and how to do it well. And I think that that was what was

so unique in in a place like San Francisco that that we could do that and many mistakes were made and there were

many many hard discussions where weighing the public health on the civil rights issues. For example, the whole

issue of closure of the bathous. These are extremely complicated issues. We face comparable issues today and and the

whole city was really involved and engaged in this. and our physicians and nurses who were by day taking care of

patients were at meetings at night with ACTUP or at the health commission or at public forums trying to answer the

questions about what is going on. And um and I think that that's one of the things that in San Francisco you

have to really appreciate is that um the strength of a response is really in direct proportion of the strength of

the institutions. And so one of the the unique things in San Francisco is that

people in San Francisco support their public health department. They do it every time a ballot measure is on the

ballot to rebuild Laguna Honda Hospital or rebuild San Francisco General where they're essentially voting against their

financial self-interest. We're agreeing to tax ourselves because we believe these institutions are really important.

We believe in the strength of community organizations and we also had to figure out how to have these conversations at

the table where scientists some of whom you're going to hear from in this course are for the first time sitting across

the table with patients and having to have these conversations about how to take care of this illness, how to do it

right and how to do it well. And um you know for me when I came to to San Francisco General in 1982 my goal in

life was to become a midwife. So here I am 30 years later and and I found myself, you know,

after the first 10 years of like, okay, how did I go from wanting to be a nurse taking care of women giving birth to

being a nurse where I'm primarily taking care of men who are dying, not exclusively men by then, but um but I

think there's something about for me as of all of these different um these different institutions and different

parts of society that have to come together to respond and to how to survive this plague. That was um that

was so compelling um that that I couldn't leave. And so here I am 30 years later and um and I

think some of those some of the reasons are the same now. And I think as the course goes on and we talk about HIV

today um and the reasons why we can be hopeful and we can be talking about a cure, the reasons why um somebody like

Lou is here with us tonight so that we can really celebrate um what his ongoing and continued contribution is to

continuing to figure out how to do this well and how to do it right. um is uh is a really compelling story and I I uh

congratulate you all for coming to this course and uh really I think you'll enjoy the speakers over the next few

weeks because it's an exciting uh uh and very compelling story. Um thank you Dion. you really uh

want to thank you personally for all you've done in the epidemic and you make the nursing profession proud. Diana is a

frequent speaker in NPR. She's she's often interviewed just about our clinic and what's happening there and uh which

has been really wonderful to have her. Our next um panelist um I wanted to ask to comment is Dr. Mark Jacobson. Dr.

Jacobson is a professor at UCSF uh an AIDS expert on our faculty who's been working in the epidemic and I'll share

with you from the very beginning. Mark, I was I I think we've heard a lot of positive and aspirational things that

we've done in San Francisco as a city, but myself being a provider going through these early dark days. Can you

comment a little bit on your experience but also what it was like and Lou alluded this to a little bit when we

were trying to get care for our patients early on often what a challenge it was when within our own profession where

people allegedly had a commitment to care sometimes that we had to overcome some obstacles.

Um I'm so yeah you can talk about your your early years and for example when we

would try to get procedures done and things like that some of the challenges that we had.

Um well I think I think at the beginning it I mean I graduated from medical school here in

1981 just before those um articles that Monica showed uh the CDC published and people had no idea what

was going on and um the the way that doctors handled it was a fullcourt press.

Um, and as it became apparent that this was an infectious disease for which there

was no effective treatment at all. Um, and it became more about just trying to make people comfortable. And when it

became apparent that people who took care of these patients were potentially at risk themselves from with exposure to

blood and doing procedures. Uh that's when um a lot of people pulled back. Not so

much in the Bay Area as other parts of this country. We're very fortunate here. Um but um it it happened here. Um and in

fact I remember um I I I finished medical school. I did a residency. I went to UCLA for two years to study

infectious diseases. And then I came back and I was hired in 1986 on the faculty here. And when I was hired here

um there was an orthopedist. There was the actually the head of orthopedics at San Francisco

General Hospital was a woman who absolutely refused to take care of or operate on people who had HIV.

And your name? Yes, it was a woman. Yes, Lorraine Day. Um, is Lorraine here tonight? No, she's

dead. Oh, I mean not good, she said, but uh but um and and things got very polarized. Uh there were surgeons were

at much greater risk, right? Because they were more likely to cut themselves than than we were. We were sticking

needles in people and sticking ourselves, especially when we were inexperienced. When I was an intern in

1981, I took care of a the first patient in the hospital I was training at who had

pneumysus and very very sick in the ICU u requiring dialysis and on a ventilator and either every other day for like

three or four weeks I had to put uh either a catheter in a deep vein in the neck or else um a tube into his abdomen

because we didn't have hemodiolysis. It was a different kind of diialysis and covered um with fluids and and I was an

intern and I was clumsy and I made mistakes, little mistakes but sometimes cut myself um

and and that kind of fear grew once we understood everybody understood that this was a virus. I mean at that point