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Ringo
01-18-2000, 08:23 PM
I realize it's hard to generalize when you consider the number of parameters that can vary, but I was wondering what the current take is on the expected continued lifespan of a person who is HIV+ but not sick these days.

I do have a friend who is + and has been for at least four years now - I spent Christmas day with him and he's healthy as can be. I know other people who are over two years since testing positive and are OK, including a couple of guys that are, well, just plain ol' fuckups who are not very good at doing what the doc tells'em to do.

OTOH, several years ago I had two friends die within a year, i.e., they developed AIDS very quickly.

The reason this came up is that someone close to me had serious need of a transfusion but absolutely refused to be transfused, for fear of contracting HIV or hepatitis. My argument to her (she yielded, she was on her third transfusion when I left the hospital this afternoon) was that these days a person identified early as being HIV+ can live 10 years or so, and dying of AIDS 10 years from now beats dying this afternoon or even this week. I later told her doctor what I'd said and he said, "Wish I'd thought of that." BTW, I didn't convince her, one of her friends did.

So, what's the scoop? Was I really way off base?

01-19-2000, 12:45 AM
It's a bit of a crap shoot...

IF you (hypothetical "you" here) are infected by a virus strain which has already mutated to become resistant to several of the current anti-retroviral agents, your life expectancy wouldn't be too much better than the 5-10 year average just before AZT first became available.

If you, for one reason or another, cannot tolerate the most effective meds, you may also have relatively fast progression of immunodeficiency. While treatment strategies for opportunistic infections have improved over the years, these are delaying tactics. Ultimately, the HIV infection will win.

No one knows how long people can maintain low or very low viral titers on anti-retroviral agents. We hope that new drugs are discovered faster than new resistance emerges. But that is asking a lot.

HIV+ individuals are starting families, hoping against hope that they will not infect their babies(the drugs really do reduce this risk), and that they will live to see their kids grow up.

I would not want to be HIV+. But I can think of several other medical conditions I would want less.



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Sue from El Paso

Experience is what you get when you didn't get what you wanted.

ubermensch
01-19-2000, 05:59 AM
the thing that struck me while reading this was that the friend was afraid of contracting HIV or hepatitis.

they do test blood for that you know. at least that's what i've always heard. sure people got HIV in the early days before they tested for it....but isn't it pretty safe now?

AWB
01-19-2000, 06:22 AM
Blood donations are tested for HIV, Hepatitis, and other disease indicators like ALT.

Plus, every donor is screened with a battery of questions, quite personal. ([For men] "Have you even once, since 1977, had sex with another man?", "Have you, in the last 12 months, had sex with someone who has had sex for drugs or money?")

Finally, before donating, they give you two barcode stickers, one for yes and one for no. They leave you alone, and if you didn't (or couldn't) answer a question correctly, or you think your blood is otherwise not suitable, you place the "no" sticker on your blood collection paraphenalia. (Perhaps your family went en masse to donate blood for a family friend, but you hadn't come out of the closet. This lets you disallow your blood for transfusion use discreteley. [They may have some other use for your blood, or they may simply destroy it.])

Since the practice of giving money for drugs has been abolished, AFAIK, donors for the most part have given blood altruistically.

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I looked in the mirror today/My eyes just didn't seem so bright
I've lost a few more hairs/I think I'm going bald - Rush

AWB
01-19-2000, 06:23 AM
ARGH.

I meant "giving money for blood" in my last post. :rolleyes:

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I looked in the mirror today/My eyes just didn't seem so bright
I've lost a few more hairs/I think I'm going bald - Rush

egkelly
01-19-2000, 07:07 AM
Since HIV has been with us now for 30+ years, shouldn't we start to see people who are immune to it? Most diseases follow a course of being very virulent at first (like measles or chicken pox millenia ago) then as the host population develops antibodies, become less deadly. (Hardly anybody dies of mumps today).
When do epidemiologists expect AIDS/HIV to start being less deadly?

Earl Snake-Hips Tucker
01-19-2000, 08:41 AM
Here's what I understand:

There seems to be a wide variation from time of HIV infection to the time symptoms start showing.

Look at Magic Johnson, for example. He was diagnosed HIV+ in 1991. He still looks pretty healthy to me.

They have some better ideas on life span as it relates to once symptoms start showing. Although, I have no idea what it is.

This is a little different, but I had the same encounter with dealing with an infected cat.

Cats can get an immunodeficiency virus, that attacks them pretty much the same as AIDS. Once symptoms start showing, the kitty goes downhill faster and faster--but, it may be years and years before that happens, or it may happen in weeks.

I get the same idea about HIV, that it sometimes takes many years before it starts showing symptoms.

I look at it as three stages, although I don't know how the medical types do it:

Point of infection
Time symptoms start showing
Time it's considered AIDS (I think that you have to have a certain number of symptoms before it's considered AIDS)
Time of death.

I think info exists on the second two time frames. It's the first that's a wild card.

I've always been interested in this question, myself, so anyone with any info--feel free to set me straight.

SqrlCub
01-19-2000, 09:16 AM
I have a friend who lives in the Suburbs of San Francisco who has full blown AIDS and has had it for about the last 20 years. He doesn't take any medication for several reasons (they are expensive and he has no health insurance plus they make him feel bad). I know his case is atypical becuase unmedicated people usually die within 10 years from opportunistic infections. Typically someone is considered to have AIDS as opposed to HIV when the opportunistic infections start occuring regularly within their bodies.

The current ideas of survival amongst those with HIV who are medicated on the coctail or whatever the current meds are is "an average lifespan" (minus a few years because the medicine that they are taking is caustic). A really good friend in Texas has been positive for about 6 years now but since the coctail he has had no discernable viral infection at all. As I said earlier, the doctors tell him that he can plan to live out a relatively normal life but he can't ever stop taking his medicine because they fear that the virus will come back if he does. When I was doing volunteer work at an AIDS hospice this wasn't the case because the coctail had just come out and they were not sure about its effectiveness.

I can answer a lot of questions regarding HIV if anyone has anymore as can most of the other gay people on the board.

HUGS!
Sqrl

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Gasoline: As an accompaniement to cereal it made a refreshing change. Glen Baxter

lvick
01-19-2000, 11:55 AM
I would not want to be HIV+. But I can think of several other medical conditions I would want less.
Well said Sue


Since the practice of giving money for drugs has been abolished,
I must have missed 60 Minutes ;) ;) ;) ;)


Since HIV has been with us now for 30+ years, shouldn't we start to see people who are immune to it?
Not necessarily, rabies and polio are both viral killers been with us for thousands of years with no sign of letting up. True we have vaccinations for them, but they are still devastating to the unprotected human.


What I'd like to know, and maybe Sue or Tubadiva can tell me is what happened to that transport enzyme they were looking into a few years ago? I remember reading, in a medical or nursing journal, that they had identified an enzyme deficiency in individuals known to have had repeated exposure without converting to HIV +. They believed that the enzyme was being used by the virus for transport across the cell membrane. Theoretically, an enzyme inhibiting drug might be able to halt the progression of the disease and our own immune system might then be able to beat it. Probably would've heard by now if they hadn't run into a brick wall, but I'm curious.

Larry,RN

torq
01-19-2000, 01:06 PM
Most of the current research I'm aware of is looking at inhibiting the HIV protease enzyme, the structure of which is pretty well known (it's shaped like a big... well, big on a molecular scale... donut). I don't _think_ this is what you're talking about, though.

Ike Witt
01-19-2000, 02:58 PM
Originally posted by egkelly:
Since HIV has been with us now for 30+ years, shouldn't we start to see people who are immune to it? Most diseases follow a course of being very virulent at first (like measles or chicken pox millenia ago) then as the host population develops antibodies, become less deadly. (Hardly anybody dies of mumps today).
When do epidemiologists expect AIDS/HIV to start being less deadly?

There are some people who are immune to some strains of HIV, I want to say that prostitutes in Kenya have been repeatedly exposed but remain uninfected. It also needs to be made clear that there are several (at least 8) different versions of HIV.

Also, I assume that in you meant Small Pox and not Chicken Pox.

lvick
01-19-2000, 04:13 PM
Actually, small pox was eradicated by an aggresive vaccination program, to the best of my knowledge there was no decrease in virulence,
Larry

Markxxx
01-19-2000, 08:04 PM
PBS did a special on this. One of gents was exposed in 1978 (or76) anyway he is still well alive and even had HIV negative kids. He takes no meds

Also they have another that was immune to AIDS. Basically they said he has a defect in his gene that prohibits the HIV from attaching itself to the cells.

But the first guy seems to have a natural immunity they haven't figured out yet.

JillGat
01-20-2000, 11:17 AM
I'm not a doctor, but I'm in the HIV/AIDS field. We've seen death rates from HIV disease all over the country drop drastically (40% and more) since the introduction of effective medical therapies in 1995/1996. Nobody knows how long this trend will continue and some drug-resistance is being seen - especially with those who have difficulty being compliant with their drug regimes - but the majority of people with HIV are doing extraordinarily well in this new era of effective therapies. We still don't have a cure, but many infected individuals have viral load laboratory tests showing undetectable levels.

Until recently, many experts advised that people start on therapies as soon as possible after infection, the theory being that maybe aggressive treatment early on would knock the virus out of commission for good, or at least keep it from replicating. A new report is coming out soon in one of the medical journals with revised recommendations, though. I'll see if I can find the email I got about this the other day to be sure what I'm about to say is accurate... If I recall correctly, new studies have shown that the side effects of these drugs can get worse over time and maybe even be life-threatening, and with the threat of developing eventual drug resistance, it's better to wait awhile - until viral loads start to go up or symptoms appear - before introducing aggressive therapy. But let me get back to you to confirm that this is what it really said.

It's true that some diseases become less virulent over time (syphilis for example), but I don't think it's because of the population developing antibodies like egkelly said. It seems more likely that the reason would be that the less virulent strains wouldn't kill their hosts so fast, so would have more time to spread to others. The most virulent strains might burn out quickly. I don't think anything like this is happening with HIV, though there is a less virulent type - HIV II - that's found mostly in parts of Africa. It's from a completely different lineage than HIV-I, not an evolutionary form of it. There are substrains of HIV-I which have variances in virulence, preferred modes of transmission, etc., but I'm in over my head if I start talking about that.

No one in our field, that I have seen, is predicting life spans for people with HIV nowadays... even for people who are or have been symptomatic. It's a completely new era, even for some of those who were on their deathbeds a few years ago. I'll tell you one thing - we practically never get reports of people with diseases like pneumocystis carinii pneumonia anymore, unless they are people who haven't been on therapy.

There are specific "opportunistic diseases" that are rare or never occur in people with normal immune systems that, along with a confirmed HIV + test, give one an AIDS diagnosis. Another criterion for an "AIDS diagnosis" is a CD4 cell count under 200. Many of these "opportunistic diseases" that give one an AIDS diagnosis have become rare again - mostly I think because of the effective protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and antiretroviral therapies allowing the immune system to keep them in check and partly because of the specifically effective prophylaxis now available against these diseases.

Some good websites for accurate information about HIV and AIDS are: www.cdc.gov (http://www.cdc.gov) and http:\\hivinsite.ucsf.edu.

JillGat
01-20-2000, 11:20 AM
Just wanted to give you another site about treatment for HIV: http://www.hivatis.org/atisnew.html

JillGat
01-20-2000, 11:48 AM
Originally posted by Markxxx:
PBS did a special on this. One of gents was exposed in 1978 (or76) anyway he is still well alive and even had HIV negative kids. He takes no meds

Also they have another that was immune to AIDS. Basically they said he has a defect in his gene that prohibits the HIV from attaching itself to the cells.

But the first guy seems to have a natural immunity they haven't figured out yet.


The guy having "HIV negative kids" doesn't mean anything, really.

Some small percentage of European-ancestored people seems to be genetically resistant to infection with HIV. It may be related to a gene these people carry that allowed their ancestors to survive some other, unrelated epidemic in Europe a long time ago. The fact is that the vast majority of human beings are susceptible to infection with HIV and there is no cure for it. Individual, rare events make good stories because they are that: rare.

JillGat
01-20-2000, 11:50 AM
Originally posted by lvick:
Actually, small pox was eradicated by an aggresive vaccination program, to the best of my knowledge there was no decrease in virulence,
Larry

Correct.

Ike Witt
01-20-2000, 01:53 PM
I understand that small pox never lost its virulence, but was chicken pox ever a mass killer?

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If I was discussing Lucy Lawless but I wrote Lucy Topless, would that be a Freudian typo?

RobRoy
01-20-2000, 03:40 PM
Individual, rare events make good stories because they are that: rare.

Scientific American - Sept. 1997, "In Search of AIDS Resistant Genes"

18 percent of Europeans have at least one resistant allele to HIV. This is more prevalent in Russia, PLoand, and Scandanavia.
+++++++++++++++++++++++++++
The problem is that all projections of progression to HIV omit the vast untested population. While a deadly disease, and one that does some in quite quickly, the statistics for time to morbitity and mortality are always working from an unrepresented total population of infected persons.

It seems that the virus is getting nastier, as 16% of new infections are already resistant to drugs (die to infection from people taking these drugs).

Ironically, some early infected individuals may have the least nasty strains, and have been subjected to overly pessimistic projections. Now a days a rosy picture is psinted, but again it may not be accurate. Recent infections, if from resistant, and evolving strains may pose a worse threat.

The early cases may have been people who were infected for many years previously, and studies going back to the mid seventies on hepatitis and venereal diseases amung gay men support this. Unfortunately the common lifestyle in the areas heavily impacted by HIV were very much in line with 70's party and drug behavior, which is a strong predictor of progression as well.

To the OP - as someone else said - it's a crap shoot. A good example of those aspects of life which are both in our control and not. It is important not to "second guess" fate and do waht one can to preserve health. Because treatments are being developed all the time, it may be a situation like diabetes. Before insulin, people died all the time from it. Then one day, there was insulin. The day before it came out - anyone who said diabetes was fatal would be right. The day after, they would be wrong. If they had predictd or anticipated the death of a friend with diabetes the day before insulin was available, they would have done them a diservice - essentially "playing god".

Your advice to your friend was good. Balance known risks of no transfusion with a minimum baseline risk of a bad transfusion.

JillGat
01-20-2000, 05:41 PM
[[The problem is that all projections of progression to HIV omit the vast untested population. While a deadly disease, and one that does some in quite quickly, the statistics for time to morbitity and mortality are always working from an unrepresented total population of infected persons.]]

I don't understand this paragraph. Are you talking about the progression from HIV to AIDS? What do you mean by "time to morbidity and mortality"? The statistics of course mostly reflect those who have tested, but we also do have a pretty good idea - at least in certain populations - of how many infected persons there are, from seroprevalence studies.

I think the data we have about HIV and progression to AIDS are actually quite good. For example, as this poster alluded to, we have a good idea of when the virus showed up in various parts of the world by looking at blood samples collected over time for other reasons (the Hepatitis B studies of gay men in California, for example). All the evidence I've seen supports the idea that this virus showed up in the US no earlier than the 70s. Where do you get the idea that "party and drug behavior" are good predictors of progression?

JillGat
01-21-2000, 12:12 AM
One more try: http://hivinsite.ucsf.edu/

RobRoy
01-21-2000, 01:57 AM
I was unclear Jill, I meant progression to AIDS (once infected), not progression to HIV, as stated.

Time to morbitity and mortality refers in this case, to average time from HIV infection to AIDS (morbitity) and death from AIDS (mortality). This is common terminology used around all kinds of disease progression estimates. The problem even with seroprevalence studies, is that the total time a person has been infected can only be determined with accuracy, if they have been tested regularly from before infection, such as the MACS study referred to above, and a single cohort (group of people) is followed. These studies have been of gay men and IVDUs in urban centers. Any broad based sero-prevalence study of the general population must have the same characteristcs (following a group over time) to effectively estimate a true figure of seroprevalance in society. Simply looking at new HIV+ test result recipients does not accomplish this - we do not know how long a person has been infected by the time they take their first test. I know of no such study of a cohort that is assembled to represent the population in general, if you do please refer me to it, I am interested in following this up. I think it is an important thing to do, but it has not been done as far as I know.

The problem with estimating the potential deadliness of the virus over the total infected population comes in when people who are outside of these traditional long-term study cohorts (closeted or married gay men, people who do not identify their own risk factors, partners of infected individuals who are kept in the dark) become sick or die of the disease. Their mortality figures up the total death figure, yet they are often not counted in the studies that follow HIV positive individuals, thus skewing the numbers of progressors to total infected.

Drug use is correlated with sero-conversion. Not all drug users convert, that is not implied by the above statement. However, seroconversion is highest in populations that exhibit high drug use, especially hard drugs, from both needle sharing and unsafe sex. This is why many interventions are targeted at these high risk groups.

As far as the progression to AIDS among HIV pos. populations in the early stages of the epidemic, these were gay urban centers where drug use and promiscuity were a cultural norm. Yes this was the late 70's, and when we begin to see HIV in blood samples. Many of these people (IMO) may have progressed quickly to AIDS by the early 80's when it was still called GRID, for several reasons that are separate from the virulence of HIV (which may have been less so at that time).

Poor health habits related to drug use

Exposure to multiple STDs that weakened the immune system

Psychological despair from lack of a treatment, and social ostracism

JillGat
01-21-2000, 07:12 PM
[[Time to morbitity and mortality refers in this case, to average time from HIV infection to AIDS (morbitity) and death from AIDS (mortality). This is common terminology used around all kinds of disease progression estimates.]]

Then you would be referring to time from morbiDity to mortality? Yeah, I've heard that terminology.

JillGat
01-21-2000, 07:19 PM
[[Drug use is correlated with sero-conversion. Not all drug users convert, that is not implied by the above statement. However, seroconversion is highest in populations that exhibit high drug use, especially hard drugs, from both needle sharing and unsafe sex.]]

You seem to be pretty knowledgeable and to have thought a lot about this. But you are also misusing the term "seroconversion" here. Seroconversion refers to the point at which an infected person's blood will show evidence of the infection - it usually does not refer to when the person becomes symptomatic.

One would assume that people who use hard drugs and party a lot would become symptomatic earlier than those who take care of themselves, but I haven't seen any studies that demonstrate that this is so. Have you? And from what I've seen (admittedly a limited sample), it isn't so.
Jill

JillGat
01-21-2000, 07:23 PM
[QUOTE]Time to morbitity and mortality refers in this case, to average time from HIV infection to AIDS (morbitity) and death from AIDS (mortality). This is common terminology used around all kinds of disease progression estimates.{/QUOTE]

Okay, I think I see what you're trying to say. You're talking about time from infection to becoming symptomatic and, separately, time from becoming symptomatic to an AIDS diagnosis. I (and I think most who work in the HIV/AIDS field) consider "morbidity" to include all those who are HIV infected. The disease is a continuum. The AIDS definition is a somewhat arbitrary term, and is becoming less and less meaningful.

RobRoy
01-21-2000, 08:42 PM
Jill, did you have any information on any study that follows a cohort meant to be representative of the general population (men women, gay bi straight, etc.) over time to determine with as much accuracy general infection rates - much like the smaller specific risk group studies?

I'd be curious - as I see the lack of any study like this (I may just be ignorant of it) as a stumbling block to a true global picture on progression rates.

Thanks.

JillGat
01-21-2000, 10:42 PM
[[Jill, did you have any information on any study that follows a cohort meant to be representative of the general population (men women, gay bi straight, etc.) over time to determine with as much accuracy general infection rates - much like the smaller specific risk group studies?]]

No, but I'm not sure exactly what the point would be. Seroprevalence studies repeated several times give us an idea of how many in certain populations are infected, and whether that number is growing. We've conducted such studies on injection drug users, patrons in gay bars, heterosexual clients in STD clinics, and youth coming through the juvenile detention center. Studies like this are conducted all over the US, along with many studies of those known to be HIV+. It would not make sense - and it would be very expensive with probable low yield - to conduct such studies on low risk populations.. if there were infections in those groups, those people would be getting sick, and they're not.

One of the largest HIV studies of any population - recently stopped for political reasons - was a blinded study testing blood collected from newborn babies (hospitals collect a drop of blood from babies when they're born to test for metabolic disorders, and some of this blood was tested for HIV without identifying the child or mother, but only collecting data on the region they were from and some demographics). Babies of HIV infected mothers will carry maternal antibodies to the virus whether the babies are infected or not. So the purpose of the study was really to find out how many women of childbearing age were infected with HIV, not how many babies were. This was an extremely useful study, and it was conducted all over the US. In this way, we had an early warning system to discover how and where the virus was spreading among heterosexuals. This information could be used to beef up testing and counseling in those areas, and public education, particularly among pregnant women (who can prevent a large percentage of perinatal transmissions by going on therapy during pregnancy).

Some people don't understand the purpose or idea of seroprevalence studies that are blinded, though, and threatened to unblind it. So the CDC stopped it before that could happen.

Anyway, it would be really pointless and unethical(in the same way the Tuskeegee syphilis experiment was) to study infected persons to see how long it takes them to progress to AIDS. We have medical treatments that are pretty effective at stopping (or slowing quite a bit) that progression now.

JillGat
01-21-2000, 10:47 PM
Here's the article I was referring to in my first post about new recommendations for when to initiate therapy in HIV infected individuals. It came out in the Journal of the American Medical Association (JAMA) day before yesterday:
[urlhttp://jama.ama-assn.org/issues/v283n3/full/jst90023.html[/url]

Jill

JillGat
01-21-2000, 11:32 PM
Sheesh, I sure have problems with links on this thread.
http://jama.ama-assn.org/issues/v283n3/full/jst90023.html
Jill

01-22-2000, 12:58 AM
RobRoy asks:

Jill, did you have any information on any study that follows a cohort meant to be representative of the general population (men women, gay bi straight, etc.) over time to determine with as much accuracy general infection rates - much like the smaller specific risk group studies?
I'd be curious - as I see the lack of any study like this (I may just be ignorant of it) as a stumbling block to a true global picture on progression rates.
Thanks.


I can't answer that question, but I can tell you where much of the early data on HIV seropositivity came from, as well as the then-heretical idea of heterosexual transmission.

The US Army (DoD, actually, but the key researchers were Army docs) initiated mass screening of all AD servicemen & women. They followed every soldier who was found to become HIV+ & developed the first "staging" system. (NB: regarding the ethics of simply observing the progression of HIV infections, that was all that was possible at the time - this was pre-AZT). Their initial findings that a high percentage of men were getting their infections from prostitutes was initially rejected by the scientific community, but later accepted. Female -> Male transmission was not thought to exist at the time. They screened family members & reported fairly high rates of infected spouses (mostly wives). They raised all kinds of red flags about HIV in women when they screened applicants & found equal rates of HIV infection in male & female 18-20 year olds from high-prevalence areas.



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Sue from El Paso

Experience is what you get when you didn't get what you wanted.

RobRoy
01-22-2000, 09:40 PM
Thanks for the info MajorMD - I can take your info with more than a grain of slat judging by your handle.

With all due respect, I'd still be sceptical about the data. No doubt the women could be infected from husbands who were self identified as exclusively heterosexual, untested and indenial about their behavior. These men are unlikely to report same sex encounters - I mean loose your health care due to a dishonorable discharge - just when you find out you have a potentially terminal disease? The study to determine risk factors should have been handled by outside scientific consultants, with assurance of anonymity.

Female to male transmission does occur, but social stigmas against reporting homosexual acts (esp. in the military) skews a study. The almost equal female and male infection rates does raise a question. Were most (or nearly all of the females) partnered to male service men who were positive? Hmmm. To find a cohort with equal numbers of male and female infected is unusual. Tell me, where did the women report their infection came from? (men, women, or IVDU?).

This is interesting stuff.

I think the need for large double blind studies is still needed to really teaseout the ambiguities, as the military cannot expect to get accurate self reported information, especially from men.

As a gay man who sees the "other side": married men, closeted military men and such, I realize that information reported outside the "gay ghetto" can be innaccurate.

RobRoy
01-22-2000, 09:43 PM
Oh another note. The almost equal infection rates in Africa for men and women are thought not to be just from heterosexual sex (or unreported homosexual sex) but from tainted blood, and innoculations which are widespread in Africa. This mechanism does not exist to such a great degree in the US.

JillGat
01-22-2000, 11:22 PM
Originally posted by RobRoy:
Oh another note. The almost equal infection rates in Africa for men and women are thought not to be just from heterosexual sex (or unreported homosexual sex) but from tainted blood, and innoculations which are widespread in Africa. This mechanism does not exist to such a great degree in the US.

Could be, to some extent, but it is also theorized that some of the substrains of HIV prevalent in Africa (and rare in the US) spread more easily heterosexually than the substrains here do. Add that to high rates of untreated, sexually transmitted genital ulcerative diseases and it seems more plausible that HIV would hit females and males equally. BTW, in New Jersey, about 30% of the cases are female. They attribute it mostly to injection drug use, though.

The comprehensive double-blind tests you're advocating, Rob, would be very expensive and there would be political opposition to them anyway. Why would they tell us more than we're learning from the targeted studies being done now, RobRoy? There are some small communities/populations I know of who claim to have a much higher rate of seropositivity than I believe to be true. They don't trust the epidemiological data that say it isn't so, and are fighting for more services and prevention programs in their communities. I think that in some cases they are motivated by the dollars available for HIV/AIDS programs. I don't doubt, however, that many of them believe it and are concerned about their people. If there were all these unknown cases in populations not generally accepted to be at high risk, wouldn't we be seeing some illness in these groups? Wouldn't they be showing up in hospitals with pneumocystis carinii pneumonia?
Jill

RobRoy
01-23-2000, 12:27 AM
It's not so much that there are vast numbers of undiagnosed HIV people out there - just that current studies are limited to pre-targeted groups and estimates of the average progression to AIDS in these groups may be an artifact of these groups. People with HIV AND NOT AIDS are undercounted compared to people with HIV AND AIDS, thus I think possibly skewing our general conception of total (or general) average time to progression.

I think the groups mentioned, in Africa, large numbers of people with untreated STD's and poor health care, the NJ women who are IVDU's, gay men who are out of the closet and part of a gay urban culture, all of these may be groups that not only contract HIV more, but also progress faster than those who do not enter the "epidemiological landscape" until they have a surprise diagnosis (through denial or honest ignorance) of AIDS.

This is speculation on my part I know, but an area that has not been investigated. Current studies have been made on the basis of some untested ideas. That "gay men" are the only ones engaging in homosexual sex. A recent Gay Men's Health Crisis poster in NY omitted the word gay and was targeted at Latino and Black men. Result - phones off the hook. Good work, but it points out that studies that look at high risk groups tell us just about the disease in those groups, not the diseae in general or the disease itself.

As a personal observation, much of the gay subculture (I'm gunna get flamed for this, but I am gay, so it's not homophobia) is centered around a bar culture and it there, in bath houses and gay magazines that cater to a bar going public that advertising and recruitement for studies cheifly occurs. I think this demographic represents a sub-culture that is multiply impacted, with HIV AND alcohol AND drug use. Same for the IVDU population.

Projections of progression to AIDS and death may be skewed in these populations. As opposed to those who - because they are not identified as gay, do not become part of the picture until they are sick with full blown AIDS, and are then ironically counted in a risk group.

It is a hallmark of alcoholism and addiction (sexual as well) that people under report the extent of their problem - that is generally true and has an influence on any estimate of the factors that are actually contributing to poor health in those studied. I've been amazed to see friends who were on meds and still drank alcohol, in spite of complications.

RobRoy
01-23-2000, 12:36 AM
I know this is a complicated point so i will try to sum it up more clearly.

We need a comprehensive, general population study to determine the REAL time to progression of AIDS - why?

Populations that are routinely followed, IVDU's, out gay men in urban centers, etc., may also be multiply impacted with other factors that negatively influence health and progression time to AIDS. (Result - overly pessimistic projections of progresion time)

AND

Populations that do not generally enroll in studies may only show up in statistics at the time of death from AIDS. This inflates the number of deaths from AIDS to the total pop. infected with HIV. (result - overly pessimistic projections of number of deaths per number of estimated HIV pos. individuals).

01-23-2000, 02:25 AM
The reason to not attempt such a study, Rob, is pretty simple.

In order to start such a study now, you would need to enroll a large cohort of newly infected patients. You would need to have several options for management (observation, early one-drug suppression, early cocktail suppression) AND not deviate from those tracks while you followed the enrollees for 10-20 years or more.

This is NOT going to happen because:

The HIV+ community is extremely well-educated on treatment options, and very insistant upon deciding for themselves what they would like to do based on the best available data. They are very likely to use alternative treatments in addition to their standard treatments & may or may not share that info with their docs. Some get several different standard treatments from different docs without telling the docs involved. I do not see them committing themselves to limiting their options to those allowed within the study.

The second big problem is that the available treatments are changing so rapidly, that no one can study them long enough to know what the long-term effects are. Realize that 10 years ago, an AZT trial was stopped prematurely because researchers found that those receiving treatment did so much better than those receiving placebo that it was unethical to continue to observe the placebo group off treatment. That's right. 10 years ago, we had NO anti-retroviral drugs. How things have changed. And remember, 10 years is the minimum length of time you could observe people now & draw meaningful conclusions. What new options will become available in the next 10 years? I don't know, but if past history is any predictor, there will be an exponential growth in the treatments available (unless a single successful cure is discovered, of course).

Actually, since I was at Walter Reed Army Medical Center from 1996-91, I can attest to the fact that the service members being interviewed as to how they might have acquired their HIV were NOT facing discharge for homosexual activity. Soldiers were NOT discharged for being HIV+; they were kept on active duty, and when the disease progressed to the point where they couldn't work, they were medically retired from active duty with full medical benefits.

I am not not expecting anyone to accept this solely on my say-so, but the Army felt gathering information on how soldiers (and all Americans) were spreading HIV was more important than keeping gays out of the ranks. The one soldier caught en flagrante in his hospital bed with another man was an exception to this open-mindedness, but that was just the last straw in a series of problems for this individual (beginning with a 45 day AWOL period).

The female=male rates of HIV+ were not for soldiers, but for applicants to active duty from high prevalence areas like NYC & NJ. On questioning, past IV drug abuse and a high number of sexual partners were found to both be present in a large number of these applicants.

If you do a MEDline search of HIV articles from the 80s & early 90s, you will see the name Robert Redfield as an author on many of these. He was the senior researcher of the Walter Reed HIV project, and an Active duty Army Colonel.

While the miltary is not a perfect cross-section of the American population, it was the first population with serial HIV testing done on a regular basis so that typically, the time an infection was acquired could be pinpointed pretty easily. A lot of the points you raise are valid concerns; however, the scientific community has recognized the value of this data, and the fact that they are unlikely to get any better data in the near future for the reasons listed above.


------------------
Sue from El Paso

Experience is what you get when you didn't get what you wanted.

JillGat
01-23-2000, 01:40 PM
[]

Rob, I am an HIV/AIDS epidemiologist for a living. It may be that I am misunderstanding you here, though. Let's see if I'm getting this right.

I am assuming that you are not suggesting that we find people who are newly infected and follow [i]them without treating them to see how long until they develop end-stage illness. Not only incredibly unethical, but pointless, as we have medications to stop that progression.

It sounds like - and I could be wrong - you are concerned that people are still thinking this is a "gay disease" and that there may be many other cases in other populations that we don't know about. The only way to get at incidence (new cases) as opposed to prevalence (how many cases there are in the population all together) is to do seroprevalence studies, and repeat them over time. This IS being done. It's also being done in emergency rooms in some places where there are a lot of cases, to see how many cases there may be out there that we don't necessarily know about. Again, it is not cost effective to do a study on the entire population. We have extremely good - the best in the world - surveillance of HIV in the United States, and there is strong evidence that our data reflect what is really going on. There are different patterns to this epidemic on the east and west coasts, in the south, and where I am, in the Rocky Mountain west. Epidemiologists do smaller studies in different areas. If there is something new and shocking that comes out of those studies, they are replicated elsewhere.

[[We need a comprehensive, general population study to determine the REAL time to progression of AIDS]]

This is an outdated concept, I think, because again, we have good therapies now. From what I have seen - and this is anecdotal, not statistical - from having personally interviewed over 200 people with an in-depth survey that asks about behavior and health, there is no obvious relationship between drug use, partying and progression to ill-health. Some of the heroin users were in great health, and some of the wealthy, educated, health-conscious gay white men progressed quickly to death. There may be studies to support or counter this observation. Again, it's just what I've seen. I would say, however, that nowadays with the importance of strictly following what may be a complicated regimen of drugs, those who have addiction or depression problems may not do this, and may indeed develop resistance to drugs and progress more quickly.

handy
01-23-2000, 02:35 PM
Annuity companies used to insure HIV people. people would actually invest their money in them. However with the new drugs, HIV people are living much longer & the investors are a bit miffed at not getting paid.

JillGat
01-23-2000, 07:39 PM
Originally posted by handy:
Annuity companies used to insure HIV people. people would actually invest their money in them. However with the new drugs, HIV people are living much longer & the investors are a bit miffed at not getting paid.

Yeah, they're called "viatical settlements," if that's what you're talking about. These companies buy life insurance policies (at less than thier value) from HIV+ people, and get the money when they pay off. I still see them advertised in magazines for HIV positive people, but it seems like a less profitable business nowadays. Fortunately.

JillGat
01-23-2000, 07:47 PM
[[In order to start such a study now, you would need to enroll a large
cohort of newly infected patients. You would need to have several
options for management (observation, early one-drug suppression, early
cocktail suppression) AND not deviate from those tracks while you
followed the enrollees for 10-20 years or more.

This is NOT going to happen because:...]]

I don't think you stated clearly enough the main reason this is NOT going to happen, Sue. It's because it would be horrifically unethical (and illegal, of course) to conduct such a study in which therapies that are known to be effective are withheld to "see what happens." I think the U.S. Public Health Service finally kind of got that message after the Tuskegee Syphilis Experiment finally ended in 1972.
Jill

01-23-2000, 08:05 PM
Actually, Jill, observation is NOT unethical as long as the observation arm included provisions for treatment once CD4 counts dropped below a certain level. More & more, docs & patients alike are questioning the wisdom of starting drugs as soon as an infection is documented.

From pre-AZT data, we know that the time from infection to opportunisitic infections averaged about 5-10 years. If patients were closely followed & drugs started as soon as CD4 counts dropped, fewer people would be on drugs, lowering costs & slowing the development of resistance. What is unknown is whether this would result in any overall decrease (or increase) in longevity of patients managed this way.

The major stumbling block is researchers inability to design a study today that is flexible enough to accomodate new developments over the next 5-10 years, and to attract HIV+ patients willing to accept randomization, blinding, and non-deviation from the assigned treatment arm.

------------------
Sue from El Paso

Experience is what you get when you didn't get what you wanted.

RobRoy
01-23-2000, 11:32 PM
I'm talking more about a purely epidemiological study. The only ethical consideration is pre and post test counseling, disclosing a positive or negative result (if that's what the person wants) and referral to medical programs.

If you wanted to use a general population cross section, you could also give people the option of not getting tested at all, yet following them over time. This would create a picture of the general population, including people who ask not to be tested.

RobRoy
01-23-2000, 11:36 PM
To clarify, there would be no arm of the study that:
1)tested
2)got a positive result
3)and withheld that information involuntarily - or forced the patient to go with out treatment

It would be a merely observational study, and not tied to testing a drug. Those do require putting patients on treatments tht work better and discontinuing ones that don't.

It may be another string, but studies sponsored by drug companies carry their own biases...

JillGat
01-24-2000, 09:19 AM
[[Actually, Jill, observation is NOT unethical as long as the observation arm included provisions for treatment once CD4 counts dropped below a certain level. More & more, docs & patients alike are questioning the wisdom of starting drugs as soon as an infection is documented]]

Offering mono-therapy instead of combined therapy is not the standard of care, and would be unethical in my opinion.

JillGat
01-24-2000, 09:20 AM
[[More & more, docs & patients alike are questioning the wisdom of starting drugs as soon as an infection is documented.]]

ps -- Yes, I included a link to the latest article about this and discussed it in an earlier post.

JillGat
01-24-2000, 09:29 AM
Rob: []

You are [i]not describing a "purely epidemiological study. To get an unbiased "section of the population," it would have to be a blinded study, without people having the ability to decline testing. As soon as we know persons are infected, it is unethical not to follow a protocol of therapy that is the latest standard. I still don't understand, at all, what you're trying to learn from this study. If it's to learn how different groups vary in how they progress with the disease, you could find those already in therapy and simply compare their outcomes. My guess is that it would be more tied to socio-economics than anything, and I'm not sure what important information this would give you.

[[If you wanted to use a general population cross section, you could also give people the option of not getting tested at all, yet following them over time. This would create a picture of the general population, including people who ask not to be tested.]]

This doesn't make any sense at all to me.

[[It would be a merely observational study, and not tied to testing a drug. Those do require putting patients on treatments tht work better and discontinuing ones that don't.]]

What are you suggesting? I still can't figure it out. I think you might want to go to www.cdc.gov (http://www.cdc.gov) and do a search. I believe you'll find that there are a multitude of studies that have been are are being conducted all over the world to get at the questions you have. There is simply not a big mystery about who is becoming infected with HIV and how. If you are concerned about "biases," then there are others I'd point the finger at way before I'd be concerned about epidemiologists.

RobRoy
01-25-2000, 09:52 PM
Chill, Jill.

Studies that focus on people who are in treatment or based on a pre-defined risk group, may be biased. Not in a hatefully political way (no finger pointing here - jeesh) but biased in a scientific way.

There is no mystery how transmission occurs, that is not the point, never was, never will be in my mind. It is about the subtle statistical biases that can creep into any study if a rigorous double blind scenario is not followed. Using sick people ready to take therapy, or only pre-defined risk groups (urban out gay men and IVDU's) is hardly an accurate picture. While making up most of the infected in the US, they are not all. Closeted gay men, non-IVDU, non-gay-identified men, etc. are not routinely followed in any way. Until they enter treatment, and are then counted as being in a risk group (or often innacurately outside of it). But in either case their lack of prophylactic treatment, early intervention etc. makes another HIV+ statistic appear on the "radar" not long before another death from HIV does. For example, I know of an African American closeted gay male (a minister), who did not get tested, finally got sick (years from HIV to AIDS totally UNKNOWN in this case - exactly my point), died 3 months later. His previous "demographic" (pos and healthy), never entered the national statistics until shortly before his death also did, same year.

To create an extreme continuum, with reality lying somewhere in between, if ALL HIV people were untracked until severe illness, the statistical figure for time from HIV+ infection to death by AIDS would be considered incredibly (innacurately) short. If on the other end, an entire cohort, representing a cross section of the population (still hard to do) was followed from ) rate of infection (let's say we start with a cohort of 16 year olds, where the infection rate (while not zero is low for the general pop.) and follow them, tracking infection rates and progression to AIDS we would have a more accurate picture for a cross section of the population over race and gender for that age cohort.

In the MACS study on Hep B the study itself was not responsible for administering treatment. People were educated and referred to treatment. It was neither withheld, nor supplied.

Thanks for the reference - check out:
http://www.cdc.gov/hiv/pubs/hivser92.pdf

This highlights a national study - using various methods. (Unfortunately I cannot cut and paste from Adobe PDF documents - please do read for yourself, there are several interesting issues raised)

Sources:
Blood sampling from mothers who are giving birth, Federal job core applicants, runaway shelters, accident victims, etc.

All attempted to cancel out "skewing factors" - I will quote here - "Previous studies in many settings suggest that those who know or suspect they may be infected with HIV or at risk for infection may be less likely to participate in HIV studies, possibly causing the sero-prevalence to decrease". The CDC sought to overcome that SCIENTIFIC BIAS in their studies. Apparently they agree with my anaylsis of the problem.

I found the study I was looking for - I'm glad they are doing it - it's a good thing. Good but not perfect. Read on. (You don't have to believe me, just check the reference)

Interestingly enough, the samples that were sent to the CDC were anonymous - to cancel the bias against people who are afraid to be tested. I'm not sure if they were asked for a general waver for "a national blood survey" etc.

People were not given treatment.

People were not told their status.

Testing was done on "discarded blood".
Some demographic information was unavailable to the testing agency, although the general profile of the clinic from which it came was.

One arm of the study used emergency room and general hospital visit discarded blood for their sample - hmmm, that wouldn't bias a higher seropositivity profile from IVDU's and people with OIs related to AIDS would it?

In the case of some arms of the study, independent ("unlinked") HIV testing and counseling was offered. Just like the MACS study - unlike double blind drug studies.

There is a ton of material in this study admitting (like any good one does) sources of potential bias. They unlike Jill do not call addessing a possibility of scientific bias "finger pointing", I'll repeat "jeeesh!". Issues of reticense to test in certain populations normally in studies, untracked behavior, and how the relative age of a cohort, even when accrurately assayed, can confuse rates of infection within a given time period, and rates of total infection over time ("attrition").

This study conscientiously address the scientific hurdles to an accurate study as outlined in my original posts - and then some. The number crunching required to randomize the data must be Herculean, but I commend them for their work. I do not confuse the results with a totally accurate picture of real HIV infection rates and time to progression to AIDS, for the general US population. In fact, more acurate than previous studies, they themselves admit possible biases.

In reply to another post -
The tuskegee experiment involuntarily withheld test results and treatment - highly unethical.

lvick
01-25-2000, 11:13 PM
probably you meant the Tuskegee experiment voluntarily witheld test results and treatment.

In fact they deliberately misled the participants about the test results and treatment options, falsely claiming to be treating them when in fact all they were doing was cataloging their slow death.

A dark chapter in in american medicine.

RobRoy
01-26-2000, 12:00 AM
Tuskegee - Involuntary to the participants.

Unlike the AIDS study cited above, at those locations where HIV tests were given (adolescent health centers, etc.) testing was offerred with conseling and referrals.

In the sites noted above which were at hospitals and the like the use of "discarded" blood was all involuntary, anonymous, and did not attempt to inform patients of their status, although I am sure that some were tested in the course of medical treatment and possibly informed under the rules governing that.

I wonder if some of the fine print on admission is a legal release of things like lost blood, removed organs etc.?

JillGat
01-26-2000, 11:01 PM
[[In the sites noted above which were at hospitals and the like the use of "discarded" blood was all involuntary, anonymous, and did not attempt to inform patients of their status, although I am sure that some were tested in the course of medical treatment and possibly informed under the rules governing that.
I wonder if some of the fine print on admission is a legal release of things like lost blood, removed organs etc.?]]

No. In blinded sero-prevalence studies (which - again - are being done in many populations, including some "general population" sites such as emergency rooms in areas of high HIV prevalence), persons are not identified, so their rights are not being violated. There is no reason to ask for permission, and the bias caused by voluntary testing is removed. If you only collect information on the results of voluntary testing programs, as Rob said, you only learn about HIV prevalence in certain populations who do not delay or avoid testing, and that doesn't give us the whole picture.

JillGat
01-26-2000, 11:04 PM
I see I misunderstood Rob's point. He was questioning whether hospitals ask patients to sign releases for discarded blood or organs. I don't believe they do, but my last post wasn't really addressing that. Sorry.

01-27-2000, 12:17 AM
Rob, while all of the study groups you mention do avoid either positive selection bias(I'm worried so I'll this study and maybe free drugs for while), or negative avoidance bias(I'm worried I won't get a job if there's a record anywhere of my being HIV+ so I won't get tested), none of them provide cross-sections of American society.

Also, while they give us some information about prevalence, they give no hint towards answering the some of the questions you raised earlier about whether widespread drug therapy & resistance is impacting the length of infection before immunocompromise occurs, because the studies do not identify individuals, or track them longitudinally.

You are right in suggesting that current longitudinal studies may underestimate (or overestimate - bias can work both ways) the denominator for calculating complication & death rates. BUT the sero-prevalence studies you cite provide NO information about numerators.

And Jill, the various study arms I suggested were off the top of my head and meant to be examples; this was not a formal proposal for a study. However, I'm not sure that the long term effects of initial therapy with one drug which is not part of the standard cocktail are well enough established to make it unethical to formally study this & prove or disprove that concept.

------------------
Sue from El Paso

Does being married to another poster make me part of a clique?

Experience is what you get when you didn't get what you wanted.

JillGat
01-27-2000, 12:32 AM
Nother coupla points..

It's pretty simple: People who test early for HIV, access treatment and take it properly don't progress to AIDS, or do so very slowly. Those who are infected but delay or avoid testing and/or don't get treatment (combination therapies) progress more quickly to AIDS. There is abundant evidence that this is so.

Blinded seroprevalence studies tell us what the prevalence of cases is in a population, but they don't tell us when people got infected. You might be able to get at incidence (new infections) if you repeated studies over time in large groups, and some do that, but again, it's very expensive.

Stepping away from sero-surveillance and just looking at surveillance (cases that are reported to the Health Department), in states where AIDS cases are counted but HIV is not yet a reportable condition, you can get a really slanted view of the epidemic. As an example, you might see a trend in which AIDS cases among white men who have sex with men are dropping sharply and cases among black females are rising quickly. This does NOT necessarily mean that white gay males are not still being infected or are even being infected at a lower rate than black females (it could be true, too, but these numbers alone don't necessarily show that). It may simply mean that the white males are testing earlier and getting treatment and the black females aren't.

Some people will look at such "trends over time" and misinterpret them to mean that prevention programs are no longer needed in the gay community. This is one of many reasons that more and more states are adopting HIV reporting instead of just counting AIDS cases, which are outdated and almost meaningless data.

A majority of "new AIDS cases" that are reported to my office are people who never tested or got treated for their infection until they came into a hospital with a possibly preventable acute illness, giving them an HIV and AIDS diagnosis at the same time.

JillGat
01-27-2000, 12:46 AM
[[However, I'm not sure that the long term effects of initial therapy with one drug which is not part of the standard cocktail are well enough established to make it unethical to formally study this & prove or
disprove that concept.]]

According to the HIV doctors I work with, mono-therapy (treating an HIV patient with only one drug, be it an antiretroviral, a protease inhibitor, or one of the others) is generally considered to be substandard care. The exceptions would be possibly pregnant women (though I believe some are now getting combination therapy) and those who have developed resistance or contra-indications with all but one drug (pretty rare). I would say this - no one would ever get a study approved in which one group received combination therapy and the other, mono-therapy.

Sue, if you disagree with me, give Abraham Verghese a call and ask him.

01-27-2000, 01:29 AM
Jill, I absolutely agree that multi drug regimens are the standard of care right now. BUT, increasingly, whether it is optimal to start patients on these regimens as soon as HIV is diagnosed is coming into question because:

1) These regimens are extremely expensive, to the point of being totally cost-prohibitive for most patients in subSaharan Africa, where the highest disease burden exists.
2) Side effects are common, and can significantly impact quality of life.
3) Widespread use increases the likelihood of newly infected persons harboring resistant strains so that even if taking a multi-drug regimen, they are getting de facto monotherapy.

While to the best of my knowledge, it is still in the "I wonder if" stage, people are considering deferred multi-drug therapy. The simplest possible study would compare outcomes between persons started immediately on standard cocktails vs persons started on standard cocktails only after developing persistantly low CD4 counts. But if it is considered ethical to defer cocktail therapy at all, I think it would also be ethical to include an arm with montherapy initially, followed by standards cocktails when/if CD4 counts fall IF the monotherapy agent is not part of the standard cocktail(s), or so closely related that resistance to it would confer resistance to cocktail agents.

This arm might provide vitally important results for patients in places where standard cocktail regimens from the time infection is diagnosed are completely out-of-reach.

------------------
Sue from El Paso

Does being married to another poster make me part of a clique?

Experience is what you get when you didn't get what you wanted.

JillGat
01-27-2000, 01:56 AM
Sue, you didn't read my earlier post in which I also cited the recent JAMA article about changing recommendations for initiating therapy in newly diagnosed patients. I also included a link to this article.

Here's another one, "Rationale for Drug Combinations in Anti-HIV Drug Therapy" http://hivinsite.ucsf.edu/medical/case_studies/2098.256e.html

This article describes how HIV becomes resistant to even very aggressive drugs if they are used alone, as monotherapy. If several drugs are used together, there is improved suppression of replication and also more mutations will have to accumulate in an HIV strain before it becomes resistant.

Experts now believe that there must be at least three drugs in a patient's
anti-HIV treatment regimen, and some recommend many more (unless there are tolerance problems). A quote from this article, "Until 1995, a common recommendation for anti-HIV therapy was monotherapy (therapy with a single anti-HIV drug, e.g. with zidovudine or didanosine alone). However, because of the rate of replication of HIV and the observation that resistance emerges rapidly with currently available drugs used alone, monotherapy is no longer recommended."

With recommendations like these, based on many, many studies, I say it would be unethical and pointless to put any group on monotherapy.

Tons of studies have been done about all of this.
Jill

RobRoy
01-27-2000, 09:12 PM
I think MajorMD addressed and summed up my previous points well.

I did not think the study cited was ideal. It sems the ideal study may well be impossible for logistical and legal reasons. The study cited was better than those that use already infected people who are progressing and trying to access drugs etc..

The "ideal" study which would most accurately estimate the average time to progression accross all demographics, would be some sort of huge study that did not select people in any way EXCEPT to create a huge cross-section of America (or the planet - let's think globally). Cohorts would have to be started when nearly all members were neg. 16 year olds for example. This does mean that, the generation of long term data would take a long time. Not logistically possible. And not very fruitful.

My argument, Jill is not for such a study. I meant to draw attention to the fact that anything less is more or less accurate, depending on the scientific bias. Depending on the method of data gathering. All studies should be viewed with an educated, critical eye. This in now way disparages the scientists and clinicians involved.

The first scientific projections of time from exposure to death by HIV were given in MONTHS, and this time frame was projected from the data available at the time, which as I pointed out above, was mainly from people who appeared as pos in the demographics, shortly before death. Or, were parts of the demographics who were urged to test - so called risk groups. Yet many who were infected then, are still alive today, and modeling the disease has become more complex in response.

Jill stated in more than a few posts that she did not understand what I was saying, yet spent much effort in replying, she also took issue and called it "finger pointing" at the epidemiologists on my part(?).

She then provided a source for a report that proved my point about scientific bias. (Thanks)

Now she has taken to arguing her point via personal email - respectfully and without personal attack I might add in all truth (I do appreciate that Jill).

I would ask that you put aside whatever professional buttons my sincere scientific inquiry posed, read the study cited, re-read my and MajorMd's posts, and not address counter arguments to statements I have not made, i.e., the means of infection.

The point I am making is subtle, it is not conclusive. Like a hypothesis it could be used to model more accurate studies (as it has in the one cited).

Irishman
01-27-2000, 10:50 PM
Don't know if anybody is actually reading this thread, but wanted to chime in here on an early comment.

egkelly:
Since HIV has been with us now for 30+ years, shouldn't we start to see people who are immune to it? Most diseases follow a course of being very virulent at first (like measles or chicken pox millenia ago) then as the host population develops antibodies, become less deadly. (Hardly anybody dies of mumps today).

Nobody dies of them because of vaccination programs. Remember all those shots you got as a kid?

Also, I've had a doctor comment to me she doesn't think HIV can be transmitted through regular, healthy heterosexual contact. She claims the transmissions are due to undiagnosed STD's. Of course her experience is limited to poor women in a free service health clinics in Mexico and Texas, so she's got an observation bias working against her.

JillGat
01-27-2000, 10:55 PM
The main point I'm trying to make is that with the great therapies we have now, most people AREN'T progressing to AIDS. This is a good thing. And those "unknown" cases who aren't being tested and aren't being treated? They show up sick pretty quickly. So no "scientific bias" is going to miss them. It's hard to miss pneumocystis pneumonia. We're not seeing lots of surprises here.. we aren't seeing many cases outside the known transmission categories. When we do, we actively investigate them (such as occupational exposure or blood transfusion cases). This was the point I made to Rob in email - that I'd be happy to give him more details about how this is done. Also, the other point I've made repeatedly and I guess I should quit now, is that the studies Rob is proposing are already being done, in every single population imaginable, though maybe not in the numbers he'd like to see. I wish he'd peruse the literature and see what I mean.
Jill

TaleraRis
01-27-2000, 11:17 PM
There really isn't a limit you can place on the amount of time that a person lives with HIV. HIV is a retrovirus and it's common with many retroviruses to lie dormant in the person's body until something causes them to become active. So you could be HIV+, have the virus in your system, and it could take you years or decades to die or you could never die from that because it never became active.

------------------
When are you going to realize being normal isn't necessarily a good thing?

JillGat
01-27-2000, 11:58 PM
Originally posted by TaleraRis:
There really isn't a limit you can place on the amount of time that a person lives with HIV. HIV is a retrovirus and it's common with many retroviruses to lie dormant in the person's body until something causes them to become active. So you could be HIV+, have the virus in your system, and it could take you years or decades to die or you could never die from that because it never became active.



I think the latest evidence shows that HIV is mildly active continuously, replicating at a low level all the time. In other words, it doesn't really become dormant. Though it's true that people can be relatively symptom-free for years, so maybe that's just getting picky.

Rob, Sorry if I've sounded exasperated or defensive. Of course there is scientific bias and we constantly evaluate our surveillance methods to try to find and address any bias we can find. No one would deny that is there. But I often deal with others' political agendas around HIV issues, too. I may be unfairly lumping you into a group in which you do not belong. For example, I often hear people argue vociferously that there is a "hidden HIV epidemic" exploding in what are considered to be "low risk groups" such as teenage heterosexuals, elderly people or a certain ethnic group. None of our evidence: surveillance, seroprevalence studies, behavioral studies, etc. show this to be true (cases occur in those groups, but not at high rates), but certain people continue to misconstrue the data to make their point, or to spread mistrust about the data because the data do not support what they want to believe is happening. This is the kind of bias that drives me nuts. In some cases these are educators who are only interested in awfulizing sex for their students and want to use our data to scare them into delaying sexual activity (while denying that any of their students might be gay, too.. most of these "sex education" curriculums I've seen are completely heterosexually based). Sometimes teacher sound downright disappointed that there are so few HIV/AIDS cases among teens in our area.. I have to remind them that this is good news.

I suspect in some other cases the motives are to get more funding for organizations that cater to these low risk groups (taking funding away from groups who respond to the needs of populations that really are being heavily impacted by this epidemic). I'm not saying that such groups do not deserve attention and funding and that many of these people aren't sincere, but I think their efforts are sometimes misguided and they are not looking at the big picture. It's unfortunate that we end up in a funding situation in which different interest groups have to compete, but that's what ends up happening, and it can be sickening to watch. We have been doing seroprevalence studies in STD clinics and youth detention centers for years and years. If there were a whole lotta heterosexual or teen cases, we'd have found them there, I think. We've found practically none (none at ALL in the youth detention facility). We've done other studies in other populations, too, as have most areas of the country.

Another thing we used to see - but not so often any more - is gay activists who want to focus on possible hidden epidemics in these other groups to draw attention away from what has been portrayed as a "gay disease" because they are tired of feeling blamed for the epidemic. This backfires, because HIV is still spreading like mad among men who have sex with men (about 75% of the cases in my state fall into this group - new cases, too), and they continue to need prevention programs and services.

As I said before, you seem pretty knowledgeable and I appreciate the discussion. I'm sorry if I've unfairly assumed motives that weren't there.
Jill

01-28-2000, 02:17 AM
Originally posted by JillGat:
Sue, you didn't read my earlier post in which I also cited the recent JAMA article about changing recommendations for initiating therapy in newly diagnosed patients. I also included a link to this article.

Actually I did read it. It's a consensus paper in which no one dares to say anything controversial. They point out the same arguments I did above for deferring treatment, and advise docs & patients to decide this jointly on a case-by-case basis. Right. In the complete absence of any data on the risks vs. benefits of immediate & deferred treatment... :rolleyes:

Here's another one, "Rationale for Drug Combinations in Anti-HIV Drug Therapy" http://hivinsite.ucsf.edu/medical/case_studies/2098.256e.html

This article describes how HIV becomes resistant to even very aggressive drugs if they are used alone, as monotherapy. If several drugs are used together, there is improved suppression of replication and also more mutations will have to accumulate in an HIV strain before it becomes resistant.

Experts now believe that there must be at least three drugs in a patient's
anti-HIV treatment regimen, and some recommend many more (unless there are tolerance problems). A quote from this article, "Until 1995, a common recommendation for anti-HIV therapy was monotherapy (therapy with a single anti-HIV drug, e.g. with zidovudine or didanosine alone). However, because of the rate of replication of HIV and the observation that resistance emerges rapidly with currently available drugs used alone, monotherapy is no longer recommended."

With recommendations like these, based on many, many studies, I say it would be unethical and pointless to put any group on monotherapy.

Tons of studies have been done about all of this.

Jill, I nave never argued that when fullscale treatment is planned, that the multi-drug regimens are the way to go.

What I have been saying is that we have no idea if immediate treatment provides enough extra benefit over deferred treatment to offset the higher costs, higher side effects rates, and higher induced resistance rates caused by widespread use of these cocktails.

I absolutely grant you that multiple drugs are more effective than monotherapy at shutting down replication, and decreasing the opportunity for mutations and resistance to occur. BUT we have no studies that show if this benefit, especially if monotherapy is limited to the pre-CD4-suppression phase, outweighs the cardiotoxity, bone marrow suppression, hepatotoxicity, & financial costs that are more likely to occur with immediate multi-drug treatment.

It is perhaps true that no IRB would approve a study with a monotherapy arm in the US. But what about in Africa, where the available money to use per HIV infected person averages ~ $3.00/year in countries in which 25% of the 20-49 year old population is infected? Maybe there, the perceived risks & benefits would be vastly different IF an inexpensive monotherapy were available to partially suppress HIV replication and transmission in the early stages of disease.

::shaking head:: I'm not really sure why I'm arguing this vociferously for a treatment arm I threw out without a lot of thought for a study I introduced as one that will never be feasible, and will never be done... But while multi-drug treatment makes a great deal of theoretical sense, and certainly appears to afford seamingly indefinite delay of opportunistic infections in a great many patients taking them here in the US, the US "epidemic" is a drop in the bucket of worldwide catastrophe from this virus. What is best here (long-term multi-drug treatment allowing people to live their full life expectancy) may not be achieveable in Africa - maybe we have to settle for allowing couples to have kids with a low risk of perinatal transmission & keeping infected adults alive long enough to finish raising their kids into adulthood. And I do maintain that monotherapy may just have a role in achieving that.

------------------
Sue from El Paso

Does being married to another poster make me part of a clique?

Experience is what you get when you didn't get what you wanted.

JillGat
01-28-2000, 04:22 PM
[[It is perhaps true that no IRB would approve a study with a monotherapy arm in the US. But what about in Africa, where the available money to use per HIV infected person averages ~ $3.00/year in countries in which 25% of the 20-49 year old population is infected? Maybe there, the perceived risks & benefits would be vastly different IF an inexpensive monotherapy were available to partially suppress HIV replication and transmission in the early stages of disease.]]

Can't you just go back and look at the AZT days in the U.S. to find out that it doesn't work and resistance quickly occurs? Or were you thinking of drug, like a protease inhibitor or non-nucleoside reverse transcriptase inhibitor?

Not to keep dragging this out when we're probably the only ones reading it at this point.

01-28-2000, 09:54 PM
Originally posted by JillGat:
Can't you just go back and look at the AZT days in the U.S. to find out that it doesn't work and resistance quickly occurs? Or were you thinking of drug, like a protease inhibitor or non-nucleoside reverse transcriptase inhibitor?

Interesting that you should bring this up. I seem to recall that the AZT trials were stopped prematurely BECAUSE AZT worked so much better than nothing. And that is all I am talking about here. Using one drug in a situation where no drug is being considered...

Once CD4 counts fall, or HIV viral load is increasing, or a person is showing any signs of immunocompromise, there is no uncertainty that multi-drug regimens are the treatment of choice. But, there IS real uncertainty about whether immediate multidrug treatment is superior to, or at least offers a better benefit/risk ratio, than no treatment until the HIV infection begins showing some adverse effects on the immune system. Which, I would think, leaves open the question of whether any single drug therapy might a) prolong that infection-to-signs-of- infection period compared with no therapy, and b) cost less/have less SE's than cocktail therapy.

I believe I've mentioned that when I originally made the suggestion, I did so off the top of my head. So, no, I didn't really think about which specific single drug might be the best candidate. Important qualities would include:
* Low cost
* Good Side Effect profile and
* resistance to this agent would not make virus resistant to planned cocktail agents. This is the most important characteristic.

Not to keep dragging this out when we're probably the only ones reading it at this point.[/B]

Why not - looks like we're in a close race for post count & this is at least semi-productive... :p

I'll draw one analogy here, Jill, that might illustrate why I think the idea of initial monotherapy followed by multi-drug therapy if the HIV load increases might just be workable.

TB is another chronic infection with a long latent period before it becomes active, highly contagious, and potentially fatal. It develops resistance quickly to antibiotics.

When treating someone with active disease, standard of care in the US is to begin therapy with 4 drugs.

When treating someone with a positive skin reaction, however, the standard of care is to treat with no drugs (if the reaction is not known to be new, there is no known exposure, and the person is >35) OR with one drug (usually INH/isoniazid) if the reaction is new (within 2 years), the person has been exposed to persons with active TB, or the person is < 35. (Disclaimer: This is accurate as of 2-3 years ago; I don't do a lot of TB care since specializing in Endocrinology, so if you know that it has changed, I'll accept that).

So while multiple drugs are always needed for advanced disease, the loss of efficacy from treating early disease with one drug is considered acceptable in the face of decreased costs, decreased side effects, & increased compliance.

This is not a perfect analogy; TB does not inevitably progress to active disease and death if left untreated. Still, prophylactic treatment with the one-drug regimen is the single most effective public health tool we have for preventing wide(r) spread epidemics of TB from occurring.




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Sue from El Paso

Experience is what you get when you didn't get what you wanted.

01-28-2000, 10:06 PM
Originally posted by Irishman:
Also, I've had a doctor comment to me she doesn't think HIV can be transmitted through regular, healthy heterosexual contact. She claims the transmissions are due to undiagnosed STD's.

I'm sorry I missed this last night.

Yes, some STD's are thought to increase the probability of viral transmission, because the inflammation associated with the STD makes the mucosal surfaces of the vagina, rectum, & urethra more permeable to virus particles, and increases blood flow just below the mucosal surface.

But anyone saying that STDs are necessary for viral transmission to occur is overly optimistic.

JillGat
01-28-2000, 10:14 PM
[[Interesting that you should bring this up. I seem to recall that the AZT trials were stopped prematurely BECAUSE AZT worked so much better than nothing.]]

But AZT stopped working in almost all who took it when they quickly developed resistance. I remember the AZT days. I lost over 20 friends and co-workers to AIDS from 1989-1992. I agree with the rest of what you said.

RobRoy
01-29-2000, 03:28 PM
The recent developments in this string bring up another issue. There are epidemiological models, and there is reality. That is a gross simplification of the arguments I made in the middle of this thread.

When it comes to treatment, because this field is rife with extrapolations about "long-term" when in certain cases a long term does not exist: average progression in the beginning of the epidemic, and noted immediately above, efficacy and "long-term" drug strategies with the recent and not so recent treatment options.

I have no question Jill that transmission is through certain behaviors (we might dispute specifics, ie oral, etc) but the main risk is unprotected passive anal sex, sharing needles, and infected blood (the last one depends more on the medical establishment of the place where you are treated - less a behavoir issue).

As far as the unprotected sex and drug use, the problem is that THE INDIVIDUALS who are doing these things are not easy to identify. The show up as a demographic, but not as individuals, for treatment, intervention or prevention, in many cases.

The poor survival rate of African Americans may be die as much to poor treatment, as no treatment and poorly targeted information.

People in general (all colors) can be a lot dumber than you think. In response to the standard, "I you are a practicing homosexual (gay) you need to do the following: blah blah" poster tacked up in a gay bar or in a bath-house, or in a magazine, has helped, but falls short in many ways.

The GMHC poster mentioned by me previously, which ommitted the word "gay" and got an in credible response. Brothers who percieve themselves as masculine and fit in to mainstream Black society, may have unsafe sex, they are not however "gay". In some communities that word has connotations that have nothing to do with the bedroom, but with a wardrobe, hand gestures and other sterotypes.

Infection rates of American teenagers are too high, due to our societal attitudes about condoms etc.

Infection rates of gey men are not declining fast enough due to the "good news" of new drugs (hardly good, but better - they are not a panacea or reason to throw out the condoms).

A prevention model that admits what we don't know, go far to investigate those "holes" in the model. Relying on gay health clinics, ads targeted at the gay community etc. neglect those who will only enter the demographics shortly before death. The current numbers for African Americans are grim testimony to this.

I think I know about this better than some epidemiologist do, I admit. Not the actual figures (my hypothesis is of an uninvestigated question - not the answers) but some of the stumbling blocks to a totally rigorous model that addresses real numbers, not those that show up from the standard methods of data collection.

Question, Jill - if you want to know how many self-identified heterosexual men are actually bi-sexual and possibly at risk, where do you look? Gay health programs? - no. Figures on infection rates of those tested? - no .Even bi men who ARE tested while being honest about being bi will lie about having a wife - so as to avoid embarrasment. There may be no provision at the facility for informing the wife, but constant political wrangling over creating such provisions scares these men, as well as the real possibility of prosecution for reckless endangerment in Illinois - if you are positive, technically you have to tell your partner, even if you do nothing to put them at risk , like being passive and requiring them to use a condom - or avoiding anal altogether.

Previous models were woefully inadequate in their sociological rigor. The term "bi-sexual sex" was actually used in some. Sex is either het- or homo-, unless it is a manage au trois, for crying outloud. Current models are better but still neglect groups that are not perceived as being high risk.

There are not vast numbers out there lurking. But the role of those outside the demographic is important in bringing infection numbers under control.

There is a strange dance that goes on behind closed doors in America. People percieve bi or "straight" men to be "safe" and both parties may get sloppy about safe sex. Any party that eschews the "gay" moniker may feel that messages do not apply to them. Teens have actually taken to anal sex, as one study reported, as you didn't ever need a condom to prevent pregnency in this act, there must not be an AIDS risk either.

AIDS is a societal roplem, not one of just individuals. Rigorous studies must team epidemiologists, sociologists, and even anthropologists in developing real effective models for determining not risk groups, BUT INDIVIDUALS AT RISK. Things have gotten better in the last 15 years and a lot of hard work has been done, but i do feel strongly from anacdotal evidence that people are slipping through the cracks.

And yes, anecdotal evidence is what is used to first posit questions, and then develop rogorous studies to then verify these hypotheses.

JillGat
01-29-2000, 11:37 PM
I agree with most of what you say, Rob.

[[Question, Jill - if you want to know how many self-identified heterosexual men are actually bi-sexual and possibly at risk, where do you look? Gay health programs? - no. Figures on infection rates of those tested? - no .Even bi men who ARE tested while being honest about being bi will lie about having a wife - so as to avoid embarrasment.]]

I know about this, too, as I worked in the anonymous testing sites for several years. I saw married men test positive and faced that quandry. This is why we use the term "men who have sex with men" instead of "gay," because there are, as you said, men who do not identify as gay who have sex with other men. These men are particularly at risk, too, because they are less likely to have a regular, intimate partner, but tend to have sex with strangers. Their wives often don't have a clue. We have intervention programs in anonymous sex venues, some of the prevention programs advertise in the personals, etc. But you are right. The prevention interventions fall far short. Until the stigma about being gay is eliminated - the major problem here, in my opinion - we're gonna have this problem.

And the guys who never test? They show up sick at some point, as you pointed out.

JillGat
01-30-2000, 03:15 AM
[[Rigorous studies must team epidemiologists, sociologists, and even anthropologists in developing real effective models for determining not risk groups, BUT INDIVIDUALS AT RISK.]]

Epidemiologists do not work in a vacuum. All studies I know of team the above groups as well as often including HIV/AIDS activists and those living with the disease to design the study protocol. We would not think of conducting a study or developing a program for injection drug users, for example, without eliciting the help of current or past injection drug users who know and have the trust of that community. Same with studies or prevention efforts in gay bars.

Use of the term "risk groups" is appropriate when discussing the epidemiology of a disease. It is less appropriate for prevention educators, because - as you alluded to - it can feel denial in those who don't want to identify with certain "risk group" behaviors or demographic attributes, and it can sound blaming.

[[i do feel strongly from anacdotal evidence that people are slipping through the
cracks.]]

So to speak.
Jill
(sorry about that, couldn't help it)

01-31-2000, 11:47 PM
I ran across this news story today. Since there seemed to be some difference of opinion about the risk of heterosexual transmission, I thought I'd share it. It would seem to contradict the widely held belief that female-to-male transmission is less likely than male-to-female...
http://www.msnbc.com/news/363534.asp?0m=N11N

Caveat: This was presented at a national AIDS meeting. It is not published yet (or peer-reviewed). There may be flaws in study design that make the conclusions debateable at best. Still... pretty interesting stuff.


------------------
Sue from El Paso

Experience is what you get when you didn't get what you wanted.

02-03-2000, 11:58 PM
Hey Jill, did you see this story?
http://www.msnbc.com/news/238328.asp

I am not saying that this supports monotherapy, but it certainly flies in the face of everything conventional wisdom would say to us about intermittant treatment of infections...

You have to question what you think you know every once in a while.

JillGat
02-04-2000, 07:46 PM
[[I am not saying that this supports monotherapy, but it certainly flies in the face of everything conventional wisdom would say to us about intermittant treatment of infections...]] No, it certainly doesn't support monotherapy. It's mostly about one single enigmatic case that has been fascinating for scientists to study. I don't know how much it tells us about the thousands of others, but hopefully something will come out of it that is useful.

02-04-2000, 08:35 PM
Originally posted by JillGat:
No, it certainly doesn't support monotherapy. It's mostly about one single enigmatic case that has been fascinating for scientists to study. I don't know how much it tells us about the thousands of others, but hopefully something will come out of it that is useful.

One? I don't think so.

from the article:
In another new trial, Lori and colleague Julianna Lisziewicz followed two groups of 10 patients whose virus levels had been controlled by drug therapy for at least two years. One group was taking the hydroxyurea/ddI combination, the others potent drug cocktails that included a protease inhibitor.
All the patients went on a drug holiday for eight weeks, with treatment resumed before then only if virus levels rebounded to unacceptable levels. The cycle was repeated several times.
The majority of the patients in the drug cocktail group had to resume therapy by week six, while none of those in the hydroxyurea/ddI group did.

Sounds like twenty to me. Not a basis for changing how patients are treated, but a basis for doing something non-conventional, something not standard-of-care, under study conditions.