AFRICA: Why did Wawer et al. stop the study examining HIV infection among sero-discordant female partners of circumcised men?

A nagging concern has arisen in the wake of a recently published study [PDF] examining HIV infection rates in female partners of HIV-positive, circumcised men. The study, authored by Wawer et al., was stopped early, reportedly due to “futility.” However, valuable information may have been lost by stopping the study early.

The clear trend was towards much greater rates of HIV infection among the female partners of circumcised men. Indeed, HIV infection sero-conversion rates were trending towards 50% or greater among these women.

The researchers called continuing the observation and collection of data an exercise in futility. If the authors were only seeking a benefit to female partners of circumcised HIV-positive men, they would be correct to describe the continued research as futile. However, why were they not also looking for a negative impact?

The relevant facts of the study are these. The male half of the couples recruited were already HIV-positive. The trend was towards higher sero-conversion among women in the couples where the male was circumcised. No additional ethical dilemmas were present in continuing to observe the trend. In fact, offering circumcision to the intact males arguably would have presented an additional ethical dilemma because, as the research parameters called for, the men were already HIV-positive. Therefore, continued observation to the scheduled completion date of the study could only have yielded more and better data, possibly rising to the level of statistical significance.

It is hard to conclude anything other than that the researchers were not looking for a negative impact and perhaps may have desired to avoid a statistically significant adverse finding to male circumcision. Johns Hopkins University, home to Bloomberg School of Public Health, has been a hot bed of research into the efficacy of male circumcision in reducing HIV risk. An adverse finding could jeopardize not only their programs, both research and roll out, centered around the belief  that male circumcision has value in the HIV/AIDS fight, but also the entire circumcision industry growing up around this latest fad in HIV/AIDS prevention.

The real reason no statistical significance was observed may be because the observers avoided that possibility.

About David Wilton

fronterizo, defense lawyer, intactivist
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6 Responses to AFRICA: Why did Wawer et al. stop the study examining HIV infection among sero-discordant female partners of circumcised men?

  1. TLC Tugger says:

    Thanks for posting this. I had the same thought.
    If this outcome doesn’t warrant continuing then nothing does. Put another way, if this didn’t warrant continuing, then they shouldn’t have started.
    But then “shouldn’t have started” applies to all these grotesque human amputation experiments and willful exposures of people to HIV.
    -Ron Low

  2. David Wilton says:

    Another thing I wonder about is if they could calculate no statistical significance at 24 months, but could predict a cumulative HIV sero-conversion rate of 13.4% among the intact (up from 12%) and 21.7 in the circumcised group (up from 18%), isn’t the ratio widening? Sure, the growing disparity is small, but small and growing must indicate something, especially as time goes on and any sero-conversion from failing to permit a period of healing recedes. Explain this to me if I’m totally missing something here.
    Another question relating to the above point about healing time is if the circumcised group were instructed to refrain from sex the recommended six weeks, then the intact group had six weeks more time to expose their female partners. Therefore, the sero-conversion gap may be larger than understood or interpreted in this paper.
    It bears noting that the infamous Ronald Gray participated in this study. Surprised the study was stopped? I’m not.

  3. Joseph says:

    It looks like it’s 1 step forward, 2 steps back.
    No sooner has news underscoring circumcision’s worthlessness been published, when the NYTimes decides to put out another creative writing piece tisking at South Africa for “lagging behind” in circumcision promotion.
    http://www.nytimes.com/2009/07/20/world/africa/20circumcision.html?_r=1&scp=2&sq=circumcision&st=cse

  4. Joe says:

    David, your post brought up some thoughts of my own regarding this issue and the halting of the study. I can see no good reason to not follow the study to completion even if there was no trend either way. If this result were to hold as true, there are some interesting implications. Especially in first world countries, heterosexually acquired HIV is associated with HIV risk individuals not the general population. High risk individual, by definition, take greater risks such as using condoms less. I suspect that they would be less likely to follow advice on condoms use after circumcision, or if they are circumcised already, and with then general knowledge that they believe they are at less risk could take even greater risks still than they might have before.
    This means they could be more frequently exposed to HIV and even if there over all risk, including reduction for risk compensation, is less, their partners could be at greater risk. Since women are already known to acquire HIV at a higher rate than men, something like 2 – 8x, an increase in their risk is not equal to a decrease in Men’s risk. That is to say that if, for example and very roughly, circumcising men were to reduce their risk by 50% but increase the risk to women by 25% this could become in essence a “push”. It is even possible that the risk to women increases to the point where overall prevalence in the adult population actually increases.

  5. Hugh says:

    “Indeed, HIV infection sero-conversion rates were trending towards 50% or greater among these women.”
    I think you mean “50% greater”. The raw figures are 18% (17/92) of the partners of circumcised men seroconverted vs 12% (8/67) of the partners of intact men.
    It is hard to see why they stopped the experiment because of “futility” and then projected those results into the future. It would have been no less ethical to have continued, since all the men were already HIV+ and they had established that circumcising the controls would not have given their partners any more protection (and might have increased their risk).
    If circumcision is shown to increase the risk to women, it would certainly be unethical to circumcise more men.

  6. David Wilton wrote: “isn’t the ratio widening? Sure, the growing disparity is small, but small and growing must indicate something, especially as time goes on and any sero-conversion from failing to permit a period of healing recedes. Explain this to me if I’m totally missing something here.”
    It is the nature of such a difference to widen the longer the study continues. By stopping the study early, they minimized the results. This is something all researchers know so it appears to be a conscious decision to misrepresent the eventual outcome. Johns-Hopkins has a long history of advocating infant male circumcision.
    David Wilton wrote: “It bears noting that the infamous Ronald Gray participated in this study. Surprised the study was stopped? I’m not.”
    No, I’m not either. Over the 130+ years infant male circumcision has existed in America, the claims have been pretty false and outrageous. Modern times, evidence and research methods have not changed this. For instance, when the vaccine against HPV, the virus responsible for cervical cancer and penile cancer was introduced 4 years ago, I accurately predicted advocates would completely ignore this development and continue to advocate male circumcision as a preventative and I have not been disappointed.
    There is a simple fact that apparently the medical community is also ignoring. If male circumcision provided the protection claimed, the US with 80% of sexually active adults would have protection as the vectors of transmission would be sufficiently broken to prevent it’s spread.
    A real world example of this is provided in our experience with polio and the Salk vaccine. Just for an explanation, Polio is a highly contagious virus and can be transmitted casually. Casual transmission can include simply touching a contaminated surface days later. The polio virus is also present in the natural environment. HIV is a relatively difficult virus to transmit due to it’s extremely short lifespan outside the body. It is not present in the natural environment outside the body. The exchange of infected blood or tissue is required for transmission.
    The Salk vaccine is “only” 70% effective. That is, only 70% of those who receive the vaccine have protection. The vaccine works by the herd immunity principle. That is, it breaks the vectors of transmission sufficiently that the virus keeps running into road blocks. The Salk vaccine wiped out the disease in a single generation. If male circumcision had the claimed effect of 61% protection, the effect would have been the same as the Salk vaccine. HIV would not have been able to make a beach head in America and it would be “One of those tropical diseases” such as malaria or ebola that affects Africa but not America. Even if we had a much smaller circumcision rate, the protection would be there.
    If male circumcision was remotely as effective as claimed, there would be stark differences in the infection rates between circumcised and uncircumcised populations. Such differences are not observed anywhere in the world.
    Mathematical models bear this out. Read http://www.aidsmap.com/en/news/23862073-490F-44F5-AC5E-17893A3764BA.asp and http://www.ias2009.org/pag/Abstracts.aspx?AID=2033 to see the effect. In her model, Lima uses a 50% circumcision rate but the circumcision rate in The US is 80%. As the circumcision rate increases, the protective factor would increase eponenitally, not a linear progression. If circumcision had the protective factor claimed, The US would be almost completely protected. Instead, The US has the highest infection rate among the industrialized countries none of which has a circumcision rate exceeding 7%.
    Now, Robert Bailey, the main motivating factor in all these studies is a professor of epidemology at The University of Chicago and would be well aware and knowledgeable of the above. The only logical conclusion is that Bailey consciously doctored the results or completely invented them. Bailey has a public history of rabidly advocating male circumcision spanning back more than 25 years. He initially advocated circumcision to the gay community in the early 1980’s when little was known about HIV including the methods of transmission. He has also recruited Daniel Halperin, another 25 year+ advocate of male circumcision. It is a logical conclusion that Bailey is simply continuing his agenda with massive financing from charitable foundations.
    Frank

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