The HIV Vaccine... Success

Comments

1
"It was definitely took an odd approach."
2
Thank you, anonymous copyeditor. I've made the correction.
3
Dear John -
Is it possible that this was just a statistical anomaly? No immune response? Seriously?
Bless you and your immense brain! :)
4
"The men and women ages 18 to 30 were recruited from two provinces southeast of the capital, Bangkok, from the general population RATHER THAN from high-risk groups like drug injectors or sex workers. "
5
@3 That’s what I was thinking. Statistical significance does not equal statistical certainty. Every so often you are going to get results that suggest an affect even though no affect has occurred. No different from how in polling you sometimes get crazy results.
6
@4: Thank. Corrected.

@3: It's possible, but there is less than a one in twenty chance (the typical standard used in scientific research) that this was due to a statistical anomaly.

There was an immune response, just not one that resulted in anti-virus antibodies. Instead, the likely response was probably from killer (CD8) T-cells destroying infected cells before they could spew out virus.

Most immune responses result in what are called neutralizing antibodies, capable of stopping the function of the free-floating virus as it travels between cells in the body. Given the extreme antigenic variation of the HIV surface proteins, this simply might not be possible for HIV. This vaccine combo worked--perhaps, speculating here--because it didn't try to contain the HIV with antibodies.
7
So, time to figure out why it protected some and not others. Personalized medicine is the next big thing, after all.
8
"And this vaccine did not lower the viral loads of people who were vaccinated but caught the virus anyway, which was baffling because even mismatched vaccines usually do that."

Because it didn't work.

The difference of only 23 among 16,000 subjects is more likely due to variations in risky behavior engaged in or different skill levels using condoms etc. All it would take is a half dozen especially careless or unlucky people in either group to throw the results off statistically.
9
Jonathan,
I haven't crunched the numbers, but very roughly this is looking to me like what you might in the business call a "two-sigma effect", meaning, the evidence ain't that great. Scientists tend to throw around the term "statistically significant" fairly loosely, and it gets the media, sometimes even the science media, all excited. If you have twenty different studies going on around the world on methods to reduce HIV risk (and you know there are more that!) then even if all twenty were totally useless, you'd expect about one of them to observe a two-sigma effect, just on the basis of randomness. So then that one group out of twenty publishes their "statistically significant" result, and the NYT's Science guy, who doesn't know better, and Stanger's Science guy, who ought to know better, get all excited. I don't know any biology, but you do, Jonathan, and reading between the lines of your post, I'm guessing that if it weren't for the "statistical significance" of the results, you'd think the mixed-drug innoculation is a crazy idea. I think your initial gut reaction, alas, was almost surely the correct one.
10
Jonathan @6: your comment came up while I was typing my comment, but I think my comment @9
anticipates and rebuts your "less than one in twenty chance [of] anomaly" assertion.
11
@9,10: Indeed. It's a two sigma effect. In biological research--particularly human clinical trials--that's about as good as it gets.

This entire field of science is more horseshoes and hand grenades than physics, sadly.

Now I'm tempted to put up a stats lesson on slog! More charts! Bernoulli distribution!
12
It's been a little while since stats class, but with a population as large as 16,000, it wouldn't take a large difference between the two groups to reach statistical significance. So I believe that the results are indeed statistically significant.

Skeptics will likely have the chance to be proven right soon, as I'd imagine this study will be highly influential and others will try to recreate or improve upon the results.
13
They also received counselling to use safer sex practices (condoms). I wonder if some of the uninfected were protected more by latex than the actual vaccination. But the placebo group received the same counseling and still got infected, so I guess it wasn't that.
14
what does "Herd immunity takes care of the rest of the risk, eventually" mean?
15
@11 It's a disservice to clinical trials to argue that the borderline level of statistical significance observed in this HIV vaccine is as good as human biological research gets.
16
@15:

Put yourself back in time, when this study was just getting started. It was a long shot. The goal was to figure out if this combo of vaccines would have any measurable effect--let alone a clinically significant effect--on HIV transmission rates or viral loads post seroconversion.

It was powered sufficiently to detect at the broadly accepted p value of 0.05 about a 1/3 reduction in risk--at the expected serocoversion rate in this population.

If anything is marginal in this study, it's the reduction in risk, not the statistical significance. Yes, with a larger study--comprised of more volunteers at extravagant cost--the statistics could've been tighter. And if the goal of this study was to definitively define a clinically successful vaccine regimen for HIV, it would be a valid critique at this point. But that wasn't the goal here.

In this sense, I think this was good human subjects research. It was done ethically, exposing the minimum number of people needed to get the answer.
17
So ... what we can say from this is that people with a genetic and environmental similarity to said Thai sex-workers might respond favorably.

Could be that people with a high-fat high-beef diet might not respond, or people with a European ancenstry might not have the correct gene segment to have the vaccine work.

Awaiting further positive study results, but it's taken a long time for trials in many other infectious diseases to get to such a promising stage.
18
(ancestry)
19
17 they weren't sex workers
20
@12: 16,000 people, the number of people in the trial, is indeed a big number. But the numbers you should compare are actually much smaller -- 74 vs 51, which are, repectively, the number of people in the placebo group and the number of people in the vaccinated group who converted to HIV positive during the five-year test period. The argument is that 51 is a smaller number than 74, and thus the vaccine works, a little -- "31.2% effective", according to one of the sillier quotes from the NYT article. Problem is this: suppose the vaccine doesn't work at all, and that the average number of people out a random sample of 8000 Thai people in five years should be 62. What you will find is that if you were to do the experiment with no vaccine at all, but with TWO placebos, call them placebo A and placebo B, then about 5% of the time you'd find that one of the placebo groups at 23 fewer cases of HIV than the other one. (Just like, in this case, the vaccine group got 23 fewer HIV conversions.)
Jonathan's error arises from his being trained as a biologist, and not as a science writer. Science writers should be able to take a broader overview than scientists, just like newspaper reporters on the weed beat should take a broader perspective than the DEA agent busting the weed smoker.
If you are a scientist studying AIDS. and you see a two-sigma beneficial effect, you write a paper. If you didn't, you wouldn't be doing your job. But if you are a journalist covering AIDS research, you should write your story like this:
"Suppose all around the world there were groups of scientists working on the hypothesis that eating a lot of a particular kind of fruit prevents AIDS. One group does a study in which they their test subjects eat two apples every day for a year. One group does the same with oranges, and so on. In all, there are twenty groups, with twenty different kinds of fruit.
At the end of the year, one group reports there amazing, two-sigma result that kiwis reduce AIDS. It's not that the scientists screwed up. It's that if you take a step back, and ask yourself how likely it is a priori that eating two pieces of fruit a day prevents AIDS, and look at all the studies, you realize that on the whole, the result is not 95% likely to be right. It is instead certainly bogus."
There's a formal way of incorporating your prior estimate that eating fruit is not going to squash the AIDS bug, called Bayesian statistics, but in cases like this, you hardly need to go to that effort.
Jonathan @16: My critique is not of the study, but of the media coverage. I think yours is a touch on the naive side, although still way way better (I venture to say more than two sigma better) than the average. If you think about what I've said, you'll realize this result is likely to be no more significant than the hypothetical kiwi study. There really are 20 groups around the world "testing different fruits." It would be different if they had had this result with a vaccine which had already shown positive results. And, sure it would be different if they can getthis result again. Just as it would be different if the kiwi result were later to reproduce.
If your estimate right now is that the vaccine is 95% likelt to have a good effect, you're nuts, to use a good statistical term.
21
A Pearson chi-squared test on these numbers gives P=0.96. Obviously, that does exceed the cannonical P=0.95 significance threshold. But equally obviously...

* It barely does. This is not a knock-your-socks-off, many-sigma result.

* It is one of a long line of studies. Do 40 studies of treatments that do nothing, and you expect 1 to pass this significance threshold.

* The infection numbers are very small, so it only takes a very small not-controlled-for effect to nullify the result.
22
@19 - they were when the French ambassador paid them $5 to sleep with him.
23
and I'd settle for two independent studies with different human population groups, @21. we've had interesting differences in Asian groups and between Europeans and Ashkenazi Jewish groups in terms of specific reactions and risk factors. Sample size of say 512 control and 512 infected with age matching, no twins, and data cleaning to remove any multi-sample repeats from people who participate in more than one trial (desperate people do things like that).
24
Just to hammer home my point @21 and Eric's point @20 above: suppose just two of the Placebo infections were due to some unaccounted for, non-random asymmetry between the treatment and control groups. (Slightly more sex partners than the treatment group, a criminal attack by a deranged sociopath, whatever.) Just moving the placebo infection count from 74 down to 72 reduces the significance to 0.94, below the cannonical 0.95 publication threshold.
25
I'm glad you brought this study up Jonathan. But what I really wish you -- or some other super-geek -- would address is whether doing vaccine research into HIV makes any sense at all from a purely public health perspective (thus, ignoring the question of its scientific interest).

With the exception of blood product contamination and vertical transmission (both virtually non-existent in the west and declining in the rest), HIV/AIDS is a behaviorally driven epidemic. If a fraction of the money that has been spent on vaccine research was diverted into actual prevention, would that be a better use of those dollars? My gut tells me yes, but I'd love to see some parsing of numbers.
27
Oo stats lesson! Do it!
(Oh god. What have I become?)
28

THE CURE for HIV/AIDS.......AMBUSH

THE IDEA that AMBUSH cures AIDS
is being proven by the more than 400 individuals who have taken a dose of 60 ml three times daily for 21 days. The result is that AMBUSH 'KILLS' the virus by causing the protein envelope to rupture and the viral particles are discarded by the white blood cells. AMBUSH is able to 'KILL' the virus that are 'hiding' in the lymph system by its 'natural radioactive' properties. This process allows the body to 'return to normal health' with a corresponding immunity to that or those strains of the virus.

What is AMBUSH ?
AMBUSH is a radioactive isotope of uranium that is found in the 'palm' plant of which there are more than 3000 species. When ingested, AMBUSH causes the body temperature in the trunk area to rise to about 102 degrees when the individual is sleeping. The preparation takes four hours per batch, which is then given to the individuals for consumption 60 ml three times daily for 21 days. AMBUSH is a herbal preparation in this form but it contains an active ingredient which is a 'NEW' crystalline substance, a drug from the 'palm plant' similarly to ASPIRIN originating from the willow tree bark

RESULTS:
After 21 days on AMBUSH, ALL the individuals experienced a decrease in viral load to undetectable, an increase in cd4, increase in RBC, an improvement in general health such as more color to the face, decrease in Buffalo hump, an increase in gluteal muscles, a decrease to having no joint pains whereby individuals can bend to touch their toes, and walk up steps are but a few examples. There is also a dramatic increase in their sexual appetite beginning after the first week of therapy

DISCUSSION:
In any plant concoction such as percolated 'tea', there are 30-40,000 compounds, whi ch would take the scientific community twenty years to isolate one particular ingredient if they knew what they were looking for. The LORD GOD has given me seven steps to isolate the active ingredient, which is soft and metallic in nature and has a carbon- uranium-sulfur-(classified)-phentolamine configuration or structure. This is similar to Federick Kekule and the discovery of the benzene ring where he dreamt the structure.

As an antiviral and 'natural radioactivity' producing agent, AMBUSH is also effective against leukemia, lupus and HPV. Here I am saying that I have 'GIVEN' AMBUSH in the same 'strength' and dosage to patients with leukemia, lupus and HPV. A 35 year old male with HIV found it difficult to impossible to urinate was put on 'green tea' and water while the doctors contemplated prostrate surgery. One of the doctors gave him my number , I sent him a supply of AMBUSH an d he has not been given any more ARV's, since taking AMBUSH 18 months ago, is in 'good' health and has expressed a willingness to be examined by HIV investigators like many others who have taken AMBUSH.

I have sent this 'IDEA' to most HIV research agencies, scientist of the field, universities, hospitals, clinics, politicians and news agencies to which it is REJECTED because the name of THE LORD GOD is mentioned. He has steered me scientifically through the processes such as which plant and how to produce the active ingredient. What are the odds of a Florida Pharmacist picking a plant would contain the CURE for HIV/AIDS ?
I have never charged any of the people for their supply of AMBUSH but a life saving has been spent on the project with NO renumeration from any sources because AMBUSH falls outside the walls of modern medicine and research.

PROPOSAL:

My proposal is that I PROVE that AMBUSH CURES HIV/AIDS by giving it to a number of END-STAGE or DRUG-RESISTANT people and the scientific community watches their recovery. This proposal addresses the problem in that I have already outlaid the results to be obtained.

This IDEA is unconventional in that the scientific community has rejected AMBUSH because I say it is GOD given. Secondly if I wrote it according to certain standards, then it might be peer reviewed. However, THE LORD GOD has also shown me that there are five enzyme systems associated with the virus, reverse transcriptase, protease, fusion and two more of which causes the virus to be AIRBOURNE. This means that without DIVINE intervention mankind and ALL warm- blooded mammals will be extinct in a number of years.

The PROOF of what I am saying is found in scientific papers wherein it is found that when the protease cuts the viral strands, it cuts it at DIFFERENT lengths EVERY time, to which it should always be a valine at the end but is a different amino acid every time. This is why it is IMPOSSIBLE to produce a VACCINE.

Since this is NOT a hypothesis but there are about 400 individuals who have taken AMBUSH, here lies a vast area in which to check, recheck and confirm that AMBUSH CURES AIDS. Let it be mentioned that during the HIV reproductive cycle, reverse transcriptase converts viral RNA into DNA compatible to human genetic materials. Thus the human DNA has been 'hijacked' and since each person has a DIFFERENT DNA, then the new viral copy is unique to that person which shows that each individual has a DIFFERENT STRAIN of the virus. Consider two HIV positive people swapping viral strains and increasing its complexity with multiple partners.
It can also be proposed that they be revisited as proof that the strain or strains that they had were 'killed' at the time of taking AMBUSH considering that a person can catch as many different strains as there are people who are infected by HIV.
I am also willing to work with the scientific community in identifying those individuals who took AMBUSH and wish to be identified with this process notwithstanding that some are stigmatized while others are jubilant,

Once AMBUSH is verified as being able to accomplish that which is aforementioned then the next stage might be the natural and artificial synthesis of the substance.

Finally, if this is accepted or not, believed or not, THE LORD GOD always wins and this is the heavenly truth to which AMBUSH was divinely given to mankind for the CURE of HIV/AIDS and it will be here forever. Apostle Shada Mishe.

apostleshadamishe@gmail.com

Here is a video taped presentation that I gave at t he Martin Luther King library in Washington

http://www.youtube.com/watch?v=8V53D1w__…
http://www.youtube.com/watch?v=vPwuwlVBO…
http://www.youtube.com/watch?v=ZejptOwMT…
http://www.youtube.com/watch?v=CqcTgIAhr…
http://www.youtube.com/watch?v=f7HPKcT_i…
http://www.youtube.com/watch?v=W9iQfgiYA…
http://www.youtube.com/watch?v=i3RzRS6tJ…