The difficulty of curing HIV, the profitability of cures, the need for research.....

“Do you ever suppose that you will see a mainstream study of a non-patentable herb that actually shows much benefit for HIV/AIDS?”

You know, I’m a pretty optimistic person, but on the other hand, I’m a realistic, so I’m torn. The reason I (and most HIV patients I know who are “long term survivors”) are cynical when it comes to natural “cures” for HIV/AIDS is that most of them haven’t worked! I don’t know how many of you remember the pre-HAART era (most of you probably don’t), but those were very desperate times: people were dying all around, and there was little mainstream medicine had to offer us (nucleoside analogues existed, but they were toxic, and didn’t seem to work very well on their own). Back in those days, HIVers had “buyers clubs” (which actually still exist in many cities), which were like co-ops where people who were HIV-positive could buy remedies that weren’t FDA-approved (from other countries, underground labs, healers, wherever! Remember, all you young’uns, this was pre-internet too!). Every other week (ok, maybe not quite that often!), there was some new “cure” offered, many of them natural, and the natural ones never seemed to work. Activists pushed for research on the few things that did seem to offer some benefit (in the lab or in people), and it was often disappointing. A lot of us also saw natural healers on our own, outside of the buyers clubs, who promised various immune boosters and other remedies. After HAART came out, a lot of us who were still alive said “screw you” to the natural healers who had been screwing us over for so many years (of course, many HIVers still do take supplements for some things, but I don’t know many people who see them as “cures”. Most people I know take multivitamins, and many smoke pot, and take various supplements for symptom relief. But very, very few, if any, still hold much belief in the ability of natural remedies to “cure” the condition. The history simply doesn’t bear it out.)

If you trace the history of HIV activism (I’m not sure whether you’re interested in this; I also doubt that there is a decent book on the subject, since the history is so recent and dynamic), you would see that there have been some shifts over the years in terms of focus (HIV activists aren’t a homogenous group in terms of goals and priorities, but you can definitely ascertain trends. There is also a tiny number of people who call themselves “HIV activists” whom 99.99% of HIVers would say do not serve our interests or represent us well, so I am not including them in this discussion). The extent to which activists have pushed for a “cure” (as opposed to focusing efforts on other goals) has definitely tending to swing back and forth. There are periods of hopefulness about cures, periods of cynicism, periods where it’s put on hold because other goals seem more immediate... But we are currently in a hot time for eradication/cure talk. There is a real interest these days, but the hunger is for serious research. HIVers have been down the alternative health claims road before. Neither I, nor any other HIV+ activists or researchers I know, would rule out the possibility that a cure will be found in some plant or other alternative protocol. However, alternative health practitioners have been promising cures (backed up with testimonials from people who may or may not have existed) for years and nobody has actually seen them deliver. On the contrary, those of us who are long-term survivors have seen many people die who were supposed to have been “cured” (I won’t get into all of the problems that HIVers have had with mainstream medicine – I suspect that I am more familiar with the specifics of them than most on this site are – but one thing that they never did was claim that antiviral drugs were a “cure”). You can therefore understand our reluctance to accept new cure claims until we have actually seen evidence of them. I can tell you that the behavior of many of those who make alternative health claims for HIV (shouting down those who ask questions; name-calling; accusing anyone who takes antiviral drugs of being a shill for big pharma) does little for their credibility and does not inspire trust.

Regarding Mr. Swanepoel’s dissertation, you asked me not to comment on it anymore on these forums, which I respected, but it’s being discussed a lot and I’m being specifically asked about it. If he wants to be taken seriously (among scientists, clinicians, and/or people with HIV), he really must publish it in a peer-reviewed journal. This is entirely possible (the data itself is publishable, although he will have to add a comment about the randomization; most people would have re-randomized in these circumstances, but since it worked in his favor, it doesn’t invalidate the results). However, the paper as a whole is not. But it can be fixed! I just now wrote him a letter responding to his reply to me, and explaining what would have to be done for the paper to be publishable (and also, why this is necessary if the Sutherlandia/Oleander mix is to attract any serious scientific interest in the United States or Europe, or among significant numbers of HIV+ people here). He needs to do some statistical tests (I tried to explain the use of the t-test in a clearer way this time. Incidentally, this would take 15 minutes max to do BY HAND. If he needs help [the real difficulty for most people is selecting the appropriate test, not running it], I will help him), the literature review needs to be shortened, appropriately sourced, and probably narrower in scope (since this will be an article reporting clinical trial results, not a review article). It’s not that difficult to get clinical trial results on an herbal compound published (it won’t be in JAMA or The Lancet, but that’s not necessarily because it’s herbal). Can I send you the comments so you can pass them on? If he believes the Sutherlandia/Oleander mix represents a viable cure, this really is what he must do if the majority of people with HIV are to consider the compound credible.

“Of of any substance that actually cures HIV/AIDS? The same for cancer”.

Eventually? Absolutely. In my lifetime? Not sure.

I’m a lot more hopeful for cancer than for HIV/AIDS (“cancer” is obviously an umbrella term. I absolutely believe that certain cancers will be cured in my lifetime. ALL cancer? Less likely. But this is really just trying to read tea-leaves!). I still doubt there will be one immune-based cure that is successful for the hundreds of different types of cancer (since anything that could cure EVERY type of cancer would probably be too likely to trigger unwanted autoimmunity), but I met a few weeks ago just for fun with an immunologist acquaintance who’s a cancer researcher (academic, not clinical; her time is spent with mice and cell lines, not humans), and the stuff they’re coming up with in the way of targeted immunotherapy is pretty incredible. It’ll always be difficult to target immune therapies at unique tumor antigens as opposed to shared ones (they just aren’t very immunogenic), but they’re now working on ways to take pieces of your own tumor, take your own immune cells (dendritic cells, the most presenters of antigen), stimulate these immune cells with the pieces of the tumor (so your immune cell recognizes it as a foreign antigen), and put the dendritic cells back inside you so that it will activate T-cells and macrophages to kill off that tumor and that tumor only. Totally drug-free. But it’s still fairly labor-intensive (still, way cheaper than chemo, radiation, or surgery! New techniques are often very labor intensive but become less so as they are improved and streamlined over the years). And that’s one of the more basic things!

HIV/AIDS is a much more difficult case than cancer. If people know that they have been exposed to the virus, and start treatment immediately, it is usually easy to “cure” (high success rate, although “cure” is still probably the wrong term. It’s called “post-exposure prophylaxis” – it’s not really a cure because the infection was never really established. Just 4 weeks of antiviral drugs prevents the virus from establishing itself [integrating] into your DNA, stops replication, and the virus dies off and is gone! This works in most, but not all, cases). Once the infection has been established (integrated into your DNA), it is much more difficult to get rid of. The virus is in your DNA. Now, if the virus is actively replicating, it’s not so hard to eliminate that T-cell with the integrated virus (activated T-cells have a finite lifespan – when an activated T-cell is infected by HIV, it usually dies in a couple days; also, other cells, such as cytotoxic lyphocytes [CTLs; CD8+ T-cells] or Natural Killer cells will kill them off by apoptosis – i.e. programmed cell death, basically giving them the ‘death signal’ and then they commit suicide). The difficulty is that HIV can hide in “resting” T-cells or “memory” T-cells, and these T-cells stay around a LOOOONG time, perhaps forever! T-cells are part of the adaptive immune system. The adaptive immune system is antigen-specific, which means that each T-cell (or B-cell, the cells responsible for making antibodies) recognize one specific antigen (in general; there are exceptions to every rule, but this is the general rule). You make millions of new T and B cells every day, most of them will die without being activated because they never meet their antigen (a T-cell specific to an antigen on the flu will die of neglect if you don’t get the flu in the near future), a few of them will encounter their antigens. When a T-cell encounters its antigen, it starts to proliferate, and makes many copies of itself (so if you have a strep infection, you now have millions of copies of the T and B cells that you need to fight off the infection that you DO have. You can see the logic of this: why should your immune system waste energy activating immune responses to all the infections you DON’T have right now? Instead, it has a potential response to millions of infections, but does not activate them until the infection is actually there. You also have an innate immune system which is not antigen-specific – i.e. it is the same response for whatever infection you get, there is no memory – but for most serious infections, you do need the adaptive responses). Most of these T-cells will become “effector cells” – they fight off infections right now; they are activated. A few of them will become “memory cells” – they are your guardians for the future: if you have strep throat, they will “remember” the strep antigen, and the next time you get a strep infection, the response will be better, faster, and stronger (this is why allergies get worse over time; this is why you often don’t get the exact same infection twice; this is how vaccines work). So, you have a naive (resting) T-cell, it meets antigen and is activated, which results in a proliferation and differentiation; after differentiation you (eventually) have 2 groups: effector cells, which remain activated, and memory cells, which revert to a resting state. Resting T-cells (naive and memory cells) have low metabolic activity and they cannot support HIV replication (which requires certain host transcr*iption factors). HIV generally infects activated T-cells, but during that period between when a memory cell is activated, and it reverts back to a resting state, it can be infected (and they are). So you have memory T-cells where HIV is integrated into the genome, but the HIV is not replicating, and this memory pool appears to be permanent. To the immune system, these cells appear indistinguishable from other memory cells. The difficulty in eradicating HIV is in the difficulty of eradicating latent reservoirs (by the way, memory T-cells are probably not the only latent reservoir). The problem with having HIV in memory cells is that they can “re-activate” (this is, after all, why memory cells exist! If you have had an immune response to Hepatitis B virus, when you are exposed to Hepatitis B again, you want your memory cells to reactivate and mount a rapid, strong response so that the infection is gone before you even know you had it! Memory responses to pathogens are far faster, stronger and better than primary responses) – even if you have eliminated all virus from the bloodstream and tissues, the reactivation of a single memory cell can bring the disease back.
There has been a lot of research on a way to eradicate these resting memory pools. It is a real challenge! The challenge is that: (1) they look no different than any other memory cell in terms of morphology, expression of surface receptors, etc. Other than killing off every memory cell in the body (which is itself extremely difficult, by the way), there is no known way to kill off those memory cells which are HIV infected. There is no known way to target the killing of these cells with a drug, monoclonal antibody, or to stimulate the immune system to kill them (this is different than with a tumor; tumors are often very clearly “altered self”, with different morphology, over-expressed cell cycle proteins... An immune response can be elicited that can recognize tumor antigens as “foreign”, even though tumors are often very good at evading these). Since it’s very tough to kill them, so far most of the research has been on activating them: if you activate an HIV-infected memory cell, one hopes that it will simply die off or be killed. However, thus far, there is the same difficulty with activating memory cells as there is with killing them: there is no good way to target this at those that are HIV-infected! It is not all that difficult to globally activate memory T-cells (e.g. IL-2 seems to do it, although nobody knows whether EVERY memory T-cell is actually being activated): activating every memory T-cell in your body is risky, and the agents that do this therefore have significant toxicity (it can even be fatal). It also doesn’t really seem to have worked so far in reducing memory reserves (activated memory cells may also revert back to memory cells; if there is not complete viral suppression, activating latent reserves can allow for infection of new T-cells, the creation of more latently infected T-cells, etc.). There was a lot of excitement a few years ago after a report that valproic acid might be able to flush HIV out of its hiding places, but this hasn’t seemed to panned out very well. Nobody has given up hope here (actually, there’s quite a bit of research and excitement and grant money along these lines – look it up if you don’t believe me), but it’s important to recognize that the challenges are not fabricated. If HIV were easily cured, an enterprising graduate student would have done it years ago.

Anyone who believes that research for a cure has not been taking place has simply not been paying attention. Last December, there was a conference of 125 scientists and researchers just to discuss the challenge of HIV eradication and new strategies for taking it on. AmFAR (the American Foundation for AIDS Research) has given out millions of dollars in grants to scientists for research on potential eradication (“cures”), and is continuing to fund such work (and is not the only one doing so). Has enough been done? From a social or political perspective, I would say “No! Enough is never being done!” However, from a scientific perspective, I would say that the progress we have made on this disease is incredible, given its complexity and the fact that it has not been with us for very long. Even drug companies do cure-based research (Merck has a lab devoted entirely to eradication; Tibotec [an interesting Belgian company that has focused on drugs that there is actually a strong NEED for, rather than me-too drugs, and has made an appreciated effort to price their drugs reasonably, within the context of the salvage drug market] has been working on gene-therapy cures).

I’m not sure how you decided that an HIV cure would not be profitable for a drug company. I think for most pharmaceutical companies, it would be EXTREMELY profitable! While HIV meds have been very profitable in recent years for a few drug companies (Abbot would be a very good example of this, with Kaletra and Norvir [they’ve been particularly evil and monopolistic on the Norvir pricing! HIV activists, doctors and patients despise them for it!]; Gilead is also doing very well with Truvada – I don’t know what percentage of their profits these drugs make up, but I would imagine its very high, especially for Gilead, since it’s a small company), but for many other pharmaceutical companies, HIV meds are not really very lucrative, and they would do much better if they suddenly had a cure. Pfizer would be a good example of this: they have three HIV meds: Rescr*iptor, Viracept (with Roche), and Selzentry. Rescr*iptor never has been and never will be used more than extremely rarely (there is broad cross-resistance between first-generation NNRTIs, so it’s a one-shot deal, and nearly everyone considers Rescr*iptor the worst choice for most people), Viracept was briefly popular (when there weren’t any good options) but quickly became obsolete (less potent than alternatives, can’t be boosted, more nauseating than other PIs) and is just about never used, Selzentry is new, was never intended for drug-naive patients, and the response to it has been very ho-hum (partly due to worries about blocking CCR5 that don’t seem to have panned out; partly due to the fact that it only works on CCR5-tropic virus, requires an expensive tropism assay, and those with advanced, drug-resistant virus who need the drug most are those who are least likely to be able to use it; and perhaps mostly because it came out during the wrong year [07-8], when too many “better” drugs were just around the corner. It’s amazingly non-toxic, but I predict that it won’t pan out as a big profit-maker. For one thing, the salvage market isn’t humongous, there will probably be some me-too drugs that do the exact same thing out soon – probably vicriviroc – that it will have to compete with, and a few years after that, they may all just be replaced by monoclonal antibodies that only have to be taken once a month or every two months). Roche is also not doing very well: it had ddC (not on the market anymore), Invirase/Fortovase (2 versions of the same drug saquinavir, the first PI released, only rarely used today), Viracept (with Pfizer, practically never used), and Fuzeon (the most complicated drug ever made, so expensive to make that despite its high price, it’s not very profitable. Plus people are leaving it in droves for Isentress, which just came out, because the injections are painful, so it will truly be the drug of last resort). So, as you can you (but just a couple examples – I could have given more!), there are a “winners” in the HIV drug market, and all of the pharmaceutical companies would like to be them, but only a few have struck it lucky. Those who are the winners may not want to jeopardize that status by finding a cure (although, if a cure is inevitable, they would rather it be them than one of their competitors). But most drug companies have not been huge winners when it comes to HIV meds. If a drug company could develop a cure, a one-time cure, that would be a HUGE windfall for them – they would literally have a monopoly, could charge any price they wanted (in the first-world at least, which is, after all, where their profits are made), and most people would pay it, because it would be cheaper than antivirals for life (not to mention the benefit of not having to take antivirals for life)! There is very little that would be more profitable for a drug company than a cure for HIV. Moreover, once HIV was cured and they made their fortune (which would be enormous, larger than any profit ever made in the history of pharmaceuticals. Incidentally, this would be far more profitable for them than continuing to let people buy antivirals, because the patents they currently hold on antiviral drugs will soon run out [a couple already have, but they are on NRTIs, and you can’t build a cocktail on NRTIs alone; also, these are not those NRTIs that anyone in the first world would take]: 10-15 years from now, there will be completely generic HAART cocktails; also, the HIV drug market in the Western world [which is where the profits are actually made] is quite finicky [which is to say fickle!]: a drug which today is “a rising star” may be dropped like a hot potato tomorrow if something more effective, or with fewer side effects comes along. Drug companies really have no way of predicting whether their antivirals will be successful or profitable [Aptivus, a protease inhibitor for PI-resistant viruses came along in 2006. It was cool on a molecular level, and it had been in development for years. Its makers obviously thought it would be successful. It probably would have been, if Prezista had not followed right on its heels and turned out to be more effective in most people with fewer side effects]. Unlike antivirals, which are a gamble, and which are very competitive, a cure would be an 100% guaranteed success (and a monopoly). They would have HIVers by the balls (so to speak), and would wring us for every penny they could get (as they’ve done in the past). If they knew how to do this, it would be the most brilliant profit-making scheme ever. That is why they are working on it! Actually, some drug companies have complained to activists (who are on their asses to develop better meds) that developing HIV meds is too time-consuming, financially risky, and expensive and that they would be better off (from a business perspective) making simpler drugs for conditions that more people in the Western world want treatments for (allergies, depression, erectile dysfunction...). Most pharmaceutical companies would LOVE to get their hands on a cure: it would make them a ton of money and put a few of their competitors (those that currently rely on antiviral drugs for profits) out of business. The only problem is the inherent difficulty of curing HIV.

“Mainstream medicine and pharmaceuticals are multi-trillion dollar for profit enterprises whose only marketplace is our bodies.”

The fact that the pharmaceutical industry is a for-profit enterprise is so indisputable it barely bares worth mentioning (since it’s something that everybody knows). I’m just not sure how that translates into cures not being profitable (or sought out). Furthermore, the vast majority of scientific research in this country is not conducted by people with ties to pharmaceutical companies.

“That is why over 75% of oncologists surveyed said they would not take chemo if they had cancer - because it is ineffectiveand the side effects are horrendous. And yet 75% of their patient are prescribed chemo. Why the discrepency? Because oncologists get to mark up their chemo drugs and 75% of their income comes from the profit of selling their patients chemo.”

I tried to find this survey. I found quite a few secondary sources (mostly altmed or ‘the secret about cancer’ pages that referred to it, but none of them carried a reference or link) quoting this, but I could not find a primary source. Do you have the primary source (i.e. the actual survey)? The recent surveys I was actually able to find were quite a bit different from this.


http://www.ncbi.nlm.nih.gov/pubmed/2379006?ordinalpos=1&itool=EntrezSystem2.P...
(patients w/ solid-tumor cancers, healthy control group, radiotherapists, oncologists, general practitioners, and cancer nurses were surveyed, asked similar questions to last one [what % chance of cure, prolonging life, or palliation of symptoms required to make treatment worthwhile with two hypothetical chemo treatments, one mild, one with severe toxicity]. Patients would take the toxic regimen if it offered a 1% chance of cure, an extra year of life, or 10% chance of symptom relief. Doctors and nurses (both those involved in cancer and those who weren’t) required much higher benefits before they would accept toxic chemo: 10-50% chance of cure, 12-24 months of life, 50-75% chance of symptom relief). However, healthy controls required a higher benefit than the doctors! 50% chance of prolonging life, 24-60 extra months, and 75% of symptom relief. This has been replicated here:


http://www.ncbi.nlm.nih.gov/pubmed/8928131?ordinalpos=77&itool=EntrezSystem2....

If that survey showing 75% of oncologists would not have chemotherapy exists (like I said, I could not find it; I tend to think that if it exists, it would be a lot more nuanced than the soundbite, i.e. “75% of oncologists would not have chemotherapy if it offered less than a 10% chance of it prolonging survival by at least 12 months”, or some other hypothetical that does not necessarily generalize to all situations), the difference, based on the surveys that I HAVE been able to find, appears to have more to do with the difference in decision-making between those who do have cancer vs. those who do not have cancer than the profit motive of oncologists. Cancer patients are apparently willing to do desperate things. In the hypothetical, they were told that the chemotherapy was toxic and had a lot of side effects. They were still willing to take it if it offered only a 1% chance of cure! This is something that is difficult for those of us without cancer to understand (although I do find it slightly infuriating when people who have never been on their deathbed with AIDS and who do not remember AIDS patients dropping like flies before the days of effective antiviral treatment question my use of antiviral drugs).

“You will see no cancer or HIV cures from mainstream medicine - and you will not see any acceptance of natural alternatives that provide cures or provide better, safer and more effective results than the hugely profitable anti-virals.”

Well, I don’t know if there ARE natural alternatives that are effective for HIV. I certainly don’t know if they are safer, better, or more effective than antivirals – that all remains to be proven I think you define “mainstream medicine” too broadly in casting your “nobody will ever accept natural therapies for HIV” critique. It is true that pharmaceutical companies will likely not ever study natural remedies that they can not patent (and actually, they could not study some of these even if they wanted to, since others have already patented them [although, if these remedies really were ‘ancient cures’, the patents could be challenged on “obviousness” grounds, but it still wouldn’t be worth their while to do so]), and they may not want others to accept them, but doctors and patients, who actually make the decisions about what treatments to use, WOULD accept them. The reason why the currently do not is: (1) they have not been proven as effective, much less more effective, than antivirals (2) nobody knows their safety profile or therapeutic index (3) it is unclear in many cases how they may interact with other drugs or herbs. This is stuff that their proponents have to show, or at least garner enough interest and data that scientists and activists will take over and show the rest (a word of honest advice: scientists and activists do not like being preached at [despite the fact that activists have a bit of a knack for preaching themselves! ;-)]. You will not win their support by telling them that they are corrupt, uninterested, or shills, even if this is what you believe. If you believe you have a cure, some might say that you have a responsibility to do all that is in your power to prove its efficacy so that it wins the acceptance of the masses – this requires scientific research. Most people will not stumble upon your books or internet sites; they will go to their doctor and do what their doctors recommend. The vast majority of doctors will follow the research. Scientists, as a group, do not respond well to polemic – this is one of those “you attract more flies with honey than vinegar” arguments [sorry for the cliche!]. Funding for research comes from all sorts of sources – most scientists are not tied to pharmaceutical companies. AIDS activists have actually funded their own research on various stuff that they think is being ignored or under-studied. Perhaps this is simply a style issue, but I don’t think the tone you use really does you [or the people you’re trying to help, assuming that the treatments you’re promoting actually work] any favors in terms of attracting more people to the cause who were not already believers.

I think there will be a cure for HIV from mainstream medicine – I just don’t know if it will be in my lifetime. Tumor elimination, in many ways, is easier (people get rid of tumors all the time! Spontaneous remissions happen! Every oncologist has seen ‘miracles’! But nobody has actually been “cured” of HIV! Everytime there used to be a ‘miraculous recovery’ prior to HAART or without antivirals, scientists would rush in and study it, and it never actually panned out. Hydroxyurea is an example of this. There is a lot of study of those who seem to not progress to AIDS as quickly as the rest of us (they’re termed “long-term non-progressors), to see what makes them different – turns out to mostly be genetics, or an occasional defective virus, (ask if you want to know the specifics – some of them are people with defective CCR5 genes or certain protective HLA alleles, or viruses with defective nef sequences).

There are absolutely cures on the horizon from mainstream science. I don’t know if HIV will be one of them. I believe that the cures in the near future will most likely come from stem cells and/or gene therapy (they would likely be here sooner if our country didn’t have its shameful policy with regards to scientific research). “Cures” are already happening! Well, for the most part, they’re in the preliminary stages. But keep your eyes peeled. It's pretty exciting stuff.
Stem cells get type-1 diabetics off insulin:
http://jama.ama-assn.org/cgi/content/full/297/14/1568

stem cells for treatment-refractory lupus:
http://www.ncbi.nlm.nih.gov/pubmed/16449618?ordinalpos=1&itool=EntrezSystem2....

gene therapy for SCID (severe combined immune deficiency; remember the boy in the bubble? these kids used to DIE! gene therapy can cure them!)
http://www.sciencemag.org/cgi/content/abstract/sci;270/5235/475

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