Dear Editor,
"Treatment Action Campaign (TAC) has welcomed research by British scientists showing that cocktails of AIDS drugs cut the rate of progression from HIV infection to full-blown AIDS by 86% compared with patients not receiving treatment."
Indeed, the article in the July 30, 2005, edition of the Lancet does say that. The article also begins by saying, "For ethical reasons, there has been no placebo-controlled randomised trial of HAART. The effectiveness of this treatment over several years is therefore unknown."
Which is what I and many other "dissidents" have been saying for years. In other words, after American taxpayers have spent a total of $170 billion on AIDS through 2005, there is still no controlled clinical study showing that people taking the antiretroviral drugs live longer or at least better lives than a similar group of people not taking the drugs. And as the Lancet authors acknowledge their study doesn't qualify either.
The authors state that, "Without trial evidence, this information must come from observational cohort studies. However, estimation of treatment effects in observational studies is not straightforward… ." Indeed it is not, yet that is exactly what the authors did by using a "novel methodology to overcome this problem".
To generate the results that so heartened TAC, the authors had to resort to a statistical method that they acknowledge "is not widely used in clinical research" and in fact "may not be widely known in the clinical research community". Yet, their results are not obtainable without this unused and unknown methodology.
Furthermore, their "results depend on the assumption that treated and untreated individuals with the same values of measured prognostic factors were similar. Prospective information about the reasons that patients remain untreated is not recorded in the database, so we cannot address this issue directly."
They also "assumed that once on therapy a patient remains on therapy."
Finally, the authors "used a combined endpoint of AIDS or death from all causes, which has been widely used in clinical HIV/AIDS research. We would have liked to examine the two endpoints separately. In the era of HAART an increasing proportion of deaths is not associated with recent AIDS-defining events, and the current definition of AIDS is no longer a near-complete marker for overall progression. We could not do so for two reasons: the number of deaths during follow-up was small, and good information on causes of deaths is lacking in the Swiss and other cohort studies."
With the help of these assumptions, considerable hand waving, and an unused and unknown methodology the authors concluded in the absence of basic mortality data that "HAART reduced the rate of progression to AIDS or death by 86%, and that its effectiveness compared with no treatment increased with time since initiation".
The authors' figure titled "Estimated effect of HAART from unweighted (standard) and weighted Cox models" captures the artificialness of their results. It shows four different results for the same data ranging from marginal (if any effect) to their 86% effect based on their "novel methodology".
Why would anyone uncritically accept such a conclusion based on flimsy data and unproved methodology when doing so entails tremendous consequences? Only a placebo-controlled randomised trial can determine whether or not a therapy prolongs or improves life compared to no therapy.
David Rasnick, PhD
Visiting Scholar
Dept. Molecular & Cell Biology
University of California at Berkeley
