Interim Review Found More Volunteers On Vaccine Became HIV+ Than Placebo

  • metta

    Posts: 54509

    Feb 09, 2020 6:48 AM GMT
    Interim Review Found More Volunteers On Vaccine Became HIV+ Than Placebo

    "The HVTN 702 study, begun in 2016, was being led by the National Institute of Allergy and Infectious Diseases (NIAID). Over 5,400 HIV-negative individuals whose ages ranged from 18-35 took part in the study across 15 sites in Africa.

    For the study, 2,694 individuals received the investigational vaccine regimen while 2,689 volunteers received a placebo.

    An interim review of the study by an independent data and safety monitoring board in January showed 129 HIV infections occurred among the vaccine recipients, and 123 HIV infections occurred among the placebo recipients."



    "While the HVTN 702 study will be halted, there are two other HIV vaccines – Imbokodo and Mosaico – currently in late-stage trials.

    Launched in 2017 in South Africa, human trials of Imbokodo (like Mosaico) attempt to invoke an immune response to a variety of HIV strains using a “mosaic” of immunogens via six injections over four sessions.

    Mosaico began trials in November of 2019 in South Africa as well but also across 57 sites in the United States, Latin America, and Europe."



    https://instinctmagazine.com/interim-review-found-more-volunteers-on-vaccine-became-hiv-than-placebo/
  • bro4bro

    Posts: 3904

    Feb 09, 2020 6:00 PM GMT
    I don't understand. Were these HIV- volunteers intentionally exposed to HIV? Or were they simply advised to engage in risky behavior with no protection? Unfortunately, the cited article gives no details at all on how the study was conducted.

    Without controlling their exposure to the virus it isn't a legitimate clinical trial. But either way, it sounds drastically unethical.
  • berimbolo

    Posts: 639

    Feb 10, 2020 1:04 PM GMT
    bro4bro saidI don't understand. Were these HIV- volunteers intentionally exposed to HIV? Or were they simply advised to engage in risky behavior with no protection? Unfortunately, the cited article gives no details at all on how the study was conducted.

    Without controlling their exposure to the virus it isn't a legitimate clinical trial. But either way, it sounds drastically unethical.


    The design of the study is a randomized controlled trial--that is, subjects were randomly assigned to receive either placebo or vaccine and then tested at standard time points later to see if they had become HIV+. The trial started in 2016, and recruited about 5400 people, requiring 6 injections over 18 months. At the time of interim analysis (which was planned), 60% of subjects were 18 months past their last injection. So that's a 4.7% infection rate in the vaccine group, and 4.6% rate in the placebo group.

    What usually happens in placebo controlled trials is that participants are told they have an X chance of getting the real treatment or the placebo one. It is highly unlikely participants were told to go out and become _more_ risky, because if the chances of being in one group vs the other was equal at 50%, you would be essentially endangering half of the participants.

    HIV incidence is much higher in Africa, with _prevalence_ rates, in some countries, in the 20% range. So, a 4-5% infection rate might not be unrealistically high for "unaltered practices", even though, that would be considered very high in North America and Europe today. Colonialism aside, this makes some African countries the best place to study HIV and related treatments/preventions, as even very small differences between treatments or between treatment and placebo detectable.

    Randomized controlled trials do not derive their power from ensuring "controlled rates of exposure", only that there is no bias in selecting individuals towards one group or the other. However, most of the time, they do result in similar proportions of risk factors between groups just from a statistical reality. The results of the study would need to be formally written up and published to know for sure and I'm hopeful that they do publish. But this isn't an unethical study, to the best of my knowledge.
  • bro4bro

    Posts: 3904

    Feb 10, 2020 5:58 PM GMT
    I guess it would depend on what the subjects were told.

    If the subjects knew they were testing a drug that might be a vaccine against HIV, it could give them false hope that they're protected, and prompt some of them to engage in riskier than normal behavior - even if they had been informed that they might be in the placebo group (I'm assuming these would not be the high IQs of the study population).

    In that case, I'd say the ethics were questionable.

    Then again, if the subjects were people who ordinarily take no precautions at all, I'd say it didn't matter what they were told.

    I think you'd still need to have some knowledge of the practices (i.e. potential for exposure) of each subject in order to make any sort of clear determination.
  • berimbolo

    Posts: 639

    Feb 10, 2020 8:29 PM GMT
    bro4bro saidI guess it would depend on what the subjects were told.

    If the subjects knew they were testing a drug that might be a vaccine against HIV, it could give them false hope that they're protected, and prompt some of them to engage in riskier than normal behavior - even if they had been informed that they might be in the placebo group (I'm assuming these would not be the high IQs of the study population).

    In that case, I'd say the ethics were questionable.

    Then again, if the subjects were people who ordinarily take no precautions at all, I'd say it didn't matter what they were told.

    I think you'd still need to have some knowledge of the practices (i.e. potential for exposure) of each subject in order to make any sort of clear determination.


    In order to pass ethics review, you have to tell the subjects that there are two groups and the chances of being in each group. While you _can_ run a deception design, they are generally very difficult to justify and you would have to demonstrate clear evidence that knowing that two groups exist and the chances of being in each group would completely wreck the design.

    The point of randomizing to two groups is to ensure that you're not biased in group allocation. At numbers as high as the thousands, individual practices blend out. There's no reason to believe that all the "higher risk-behaviour" subjects ended up in one group and not the other. And if that _was_ the case, then the results actually REALLY show that the vaccine doesn't do anything, because in order for a vaccine to be effective, it has to do BETTER than the placebo by a lot. If all of the high-risk individuals ended up in the vaccine group, it would still need to have an infection rate much less than 4.7-ish% to be worth using. If all of the high-risk individuals ended up in the placebo group, then it would be evidence towards the idea that risky behaviour has basically no contribution to infection rates.

    And even if everyone was told, "Go ahead, be risky now," the vaccine still wouldn't be worth using, because there's STILL no difference in infection rates worth talking about.
  • bro4bro

    Posts: 3904

    Feb 11, 2020 1:27 AM GMT
    Yes, I understand that the vaccine is worthless. It made no measurable difference whatsoever (the slightly greater number of infections among the group who was given the vaccine is not statistically significant).

    And I understand that the subjects were told half of them would be receiving a placebo.

    The ethical question I have in mind is whether the subjects were told what the drug they were being given was intended to do - and if so, were they either educated or intelligent enough to understand that a) even if they get the vaccine, it might not work, and b) they're just as likely to be receiving something that certainly won't work.

    Once again, if these subjects ordinarily take no precautions at all then there's no point worrying about the ethics of the study. But I'm thinking about how quickly the gay community here in the US embraced PrEP as a magic bullet that would allow them to ignore the possibility of being infected with HIV and engage in limitless risky behaviors at a time when the true effectiveness of the drug and its long term side effects are still essentially unknown. It's clear evidence of magical thinking at play when you realize that many of the very same people who swear by PrEP have an extreme distrust of the pharmaceutical industry when it comes to virtually everything else.

    Passing an ethics review is one thing. Truly ethical behavior is another. I don't know that anything was done in this study that I would consider wrong but I can imagine such things might occur - which is why I asked the question.
  • Posted by a hidden member.
    Log in to view his profile

    Feb 15, 2020 11:50 PM GMT
    Ethics standards have in general become stronger, reason is due to legal risks, however manipulation of key elements of some studies has led to falsifying of results which although not common place has become more exposed. The main source is errors of ommision and manipulation of the control groups. This study coming up with a negative result indicates highly likely the above is not occurring. Regarding HIV- guys exposure in trials, my understanding is they would have been identified as statistically likely to continue risk-behavior regardless and would be aware they may have the placebo.