BEST TREATMENT FOR HIV: THIS YEAR’S ADVICE, LAST YEAR’S, OR NEXT YEAR’S?
Posted by Henry Bauer on 2007/12/10
Antiretrovirals are often referred to as “life-saving” drugs. Wainberg even says that they enable many HIV-positive people to “survive indefinitely with good quality of life”. By contrast, the NIH Fact Sheet reports deaths “from liver failure, kidney disease, and cardiovascular complications” in the first decade of HAART (“cocktail”) therapy, and the largest study to date (of 22,000 patients) found that the drugs do not decrease mortality–in other words, they don’t save lives (Wainberg’s Hammer, 5 December).
Further help in assessing these opposing views comes from the Treatment Guidelines issued by the National Institutes of Health. However, I would caution HIV-positive people against reading this document, because it inspires little confidence in the grounds for its recommendations.
For one thing, these Guidelines change, and not infrequently. I was annotating the version of 10 October 2006 when I found that it has been superseded by a 1 December 2007 edition. Not only that: the latter’s front cover already warns that “concepts relevant to HIV management evolve rapidly”. Page i then lists changes from the previous guidelines and foreshadows further changes as well, to be released in 2008.
For another thing, recommendations are ranked by criteria that have two parts. A, B, C, D, E reflect the “strength of recommendation” as judged by a panel of experts; the grades correspond respectively to “strong”, “moderate”, “optional”, “should not usually be offered”, “should never be offered”. Roman numerals I, II, III represent the “quality of evidence for recommendation”:
I: at least one randomized trial with clinical results;
II: clinical trials with laboratory results;
III: expert opinion.
It inspires little confidence when the highest quality of available evidence calls for no more than a single randomized trial with clinical results, which means, whether the patients actually improve under treatment. In other circumstances than HIV/AIDS, clinical results of a single randomized trial, even if double-blinded, would merely be reason to carry out more trials in order to confirm or disprove that result. After all, the usual criterion for “statistical significance” is p ≤ 0.05, a 19 in 20 chance that the result is trustworthy–which is also a 1 in 20 chance that it is not, perhaps too high an uncertainty when it comes to matters of fatal diseases and toxic drugs. Moreover, 1 in 20 is only the mathematical chance that the result is wrong; additional uncertainty comes from the fact that protocols are rarely perfect or perfectly adhered to, humans make mistakes, and unforeseeable variables or circumstances may have played a role. A single non-blinded trial is not much to rely on.
II is what was paraphrased in my post of 5 December as “operation succeeds, patients dies”. Lab results are merely surrogate markers; the only thing that ought to matter is the outcome for the patient. Moreover, a number of publications have reported that in fact these surrogate markers do not necessarily correspond with better outcomes for patients (for example, Antiretroviral Collaboration, Lancet, 368  451-8); and furthermore the two commonly used surrogate markers, CD4 counts and viral load, do not even correlate significantly with one another (for example, Rodriguez et al., JAMA, 296  1498-1506).
III, “expert opinion” as “quality of evidence” implies that there is no scientific evidence on which to base an opinion.
Indeed, this whole set of criteria, I to III, indicates that there is really very little in the way of appropriate scientific data on which to base treatment. Beyond that, it is puzzling, troubling, incongruous to find that the strength of recommendation does not correlate with the quality of the evidence. One finds all the combinations AII, BII, CII, DII, EII and AIII, BIII, CIII, DIII, EIII, and even the occasional BI. So “strong” recommendations may be based on no evidence beyond expert opinion (AIII), while occasionally a merely moderately strong recommendation results from evidence based on an actual clinical trial (BI). Recommendations from “strong” all the way to “should never be offered” may be based either on trials with laboratory results or solely on “expert opinion”.
Pity the physician who must advise an HIV-positive patient, when the official guidelines are so insecurely based on scientifically reliable knowledge. The warning that guidelines change frequently makes the physician’s task yet more onerous, asking that a daily check be made at the pertinent website. And as if that were not enough, the Guidelines are quite ambivalent about interruptions of treatment, which are however obviously necessary if treatment is to be modified in accordance with a changed recommendation.
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These deficiencies in the official treatment guidelines underscore the desperate need to learn exactly what produces a positive HIV-test in each individual instance. Current practices ignore the demonstrable fact that testing HIV-positive does not necessarily show the presence of active infection by an agent that destroys the immune system:
—Johnson (http://virusmyth.net/aids/data/cjtestfp.htm) cites 64 scientific articles that found 66 conditions capable of producing a false-positive test, conditions ranging from as harmless as vaccination against flu or the presence of normal human ribonucleoproteins to as serious as cirrhosis, malaria, myeloma, or tuberculosis.
—The epidemiology of HIV tests in the United States shows that what is typically detected is not a sexually or otherwise transmitted infectious agent.
—Test kits, whether for antibodies (ELISA, Western Blot) or viral RNA, are annotated with disclaimers that the tests cannot be used validly for diagnosis of HIV infection.
Despite these facts, anyone who tests HIV-positive is typically presumed to be infected with HIV. That person’s physician is then confronted with highly complicated, indeed confusing guidelines for offering advice. The stakes are as high as life and death: if the positive test actually stems from a harmless condition, toxic “treatment” may be advised by physicians who prefer to take action than to not take action in ambiguous circumstances. On the other hand, if the positive test stems from a serious condition like malaria or myeloma, the physician may be led to recommend toxic chemotherapy instead of the correct treatment for the actual condition.
HIV tests are most likely to be undergone by those in high-risk groups. False positives among people who seem to be at little or no risk may well be checked carefully and repeated a number of times, with the likelihood of eventual negative results, or even shrugged off if the physician is sure enough that the patient couldn’t have been infected. For example, should a positive test result in the case of one of the celebrities who take HIV tests as an encouragement to others–high-risk people–to be tested, one may be quite sure that no effort will be spared to find some way of judging it a false result. So the people most at risk of inappropriate antiretroviral treatment as a result of HIV testing are those in the classic high-risk groups of gay men and drug abusers; to which in recent years have been added African-Americans who seem always, in every group, to test positive more frequently than others. If only for the sake of people in those groups, there is a desperate need to find out precisely what has produced the positive HIV-test in every individual instance so that subsequent actions can be as beneficial and as little harmful as possible. That information is also desperately needed in order to understand why some proportion of patients have experienced symptomatic relief from antiretroviral treatment; it has been pointed out, for example, that the relief could stem from antibacterial or antifungal action of these drugs rather than from antiviral action.
This entry was posted on 2007/12/10 at 2:16 pm and is filed under antiretroviral drugs, experts, HIV risk groups, HIV tests, prejudice. Tagged: antiretroviral drugs, changing antiretroviral drug recommendations, evidence-based treatment, expert opinion, opinion and evidence. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.