In earlier posts I commented on how ever-changing are the official Guidelines for the use of antiretroviral drugs in “HIV-1 infected” people and how doubtfully based on reliable scientific evidence (“BEST TREATMENT…, 10 December), as well as euphemistic about toxic “side” effects (ANTIRETROVIRAL DRUGS, 12 December). Here are a few bits (from the October 2006 version) to illustrate why my view of these Guidelines is such a jaundiced one. If you suspect that these extracts may be misleadingly out of context, reassure yourself that they are quite representative by reading the latest version, freely available via the Internet.
Page 2: “short term and, even more concerning [sic!], longer term toxicity may limit the duration of treatment needed in what can be seen as a chronic disease. Finally, drug interactions among the antiretroviral drugs and with other necessary drugs are challenging and require special attention in prescribing and monitoring”.
Apart from the clear and worrying statement that prescribing and monitoring are challenging because of numerous interactions with many medications, it’s rather baffling, why longer term toxicity should be of more concern than short-term toxicity? Is this another instance of what has been remarked in some earlier posts, that the experts do not necessarily think about what they are saying or calculating?
If duration of treatment is limited by “short term … toxicity”, that means the patient died or was severely harmed already by a brief course of treatment. How could this be of less concern than “longer term toxicity”? Only if the preoccupation is with treating long enough to kill the virus, forget about the patient.
“—Antiretroviral therapy is also recommended for asymptomatic patients with <200 CD4+ T cells/mm3 (AI).
—Asymptomatic patients with CD4+ T cell counts of 201–350 cells/mm3 should be offered
— For asymptomatic patients with CD4+ T cell of >350 cells/mm3 and plasma HIV RNA >100,000 copies/mL most experienced clinicians defer therapy but some clinicians may consider initiating treatment (CII).”
The strongest recommendation, AI (for definitions, see post of 10 December, BEST TREATMENT…), is for antiretroviral treatment for people with no symptoms of illness, purely on the basis of a low CD4-cell count, which in Canada is not even regarded as a reason for treatment (www.phac-aspc.gc.ca/publicat/haest-tesvs/a_e.html, accessed 28 April 2006). That underscores, of course, why “The decision to begin therapy for the asymptomatic patient is complex and must be made in the setting of careful patient counseling and education”.
Indeed! “Asymptomatic” people–people with no sign of ill health–are in these Guidelines recommended strongly (A), moderately (B), or optionally (C) to start “treatment” which in healthy people produces such results as “depression, chronic fatigue, loss of weight and appetite and inflammation of the intestine”.
That description is from a report about a woman wrongly diagnosed as HIV-positive who was recently awarded $2.5 million in damages for malpractice (“Woman misdiagnosed with HIV gets $2.5 M”, Rodrique Ngowi (AP) 13 December 2007). Perhaps some enterprising lawyer will organize a class-action suit against the people who draw up these Guidelines, since they call for asymptomatic people to be fed substances known to be toxic, recommendations made (“offered” to the “patient”!) solely on the basis of lab tests (CD4 counts) that are not universally recognized as validly diagnostic or (“HIV” tests) that are known to be subject to many false positives (http://virusmyth.net/aids/data/cjtestfp.htm) and which have never been proven to detect active virus (SKEPTICISM…, 12 November).
Page 9: “The optimal time to initiate antiretroviral therapy among asymptomatic patients with CD4+ T cell counts >200 cells/mm3 is unknown. For these patients, the strength of the recommendation for therapy must balance other considerations, such as patient readiness for treatment and potential drug toxicities”.
The phrase beginning “patient readiness” signals clearly enough that nasty side effects are to be expected.
Page 12: “With improved choices of more effective and more convenient regimens, some of the agents or combinations previously recommended by the Panel as alternative regimens have been removed from the list or placed as other possible options”.
Consider how the physician and the patient feel when the treatment they had agreed on and used is removed from the list of recommendations. Give thought to why those previously recommended regimens were withdrawn.
Page 13: “two deaths were attributed to nevirapine use . . . . Symptomatic, serious, and even fatal hepatic events have been observed when nevirapine was initiated in treatment-naïve patients. . . . In some cases, hepatic injuries continued to progress despite discontinuation of nevirapine”.
[Translation: People treated with nevirapine have suffered liver damage that gets worse even after the treatment stops.]
Pages 20-21: “Adverse effects have been reported with virtually all antiretroviral drugs and are among the most common reasons for switching or discontinuation of therapy and for medication non-adherence [emphasis added] . . . in a Swiss HIV cohort . . . 47% and 27% of the patients were reported to have clinical and laboratory adverse events, respectively . . . . Whereas some common [emphasis added] adverse effects were identified during pre-marketing clinical trials, some less frequent toxicities (such as lactic acidosis with hepatic steatosis and progressive ascending neuromuscular weakness syndrome) and some long term complications (such as dyslipidemia and fat maldistribution) were not recognized until after the drugs had been used in a larger population for a longer duration. In rare cases, some events may result in significant morbidity and even mortality.”
Bear in mind that new drugs continue to be introduced, on the basis of similarly brief trials, even though they belong to the same classes of substance as those already known to bring “long term complications”.
“Complications”, of course, is yet another euphemism for really serious sickness or death.
Page 21: “Most drug interactions with antiretrovirals are mediated through inhibition or induction of hepatic drug metabolism . . . . The list of drugs that may have significant interactions . . . is extensive and continuously expanding [emphasis added]. . . . lipid-lowering agents (the “statins”), benzodiazepines [tranquilizers--librium, valium, xanax, etc.], calcium channel blockers [for cardiovascular conditions], immunosuppressants (such as cyclosporine, and tacrolimus), anticonvulsants, rifamycins [antibiotics, typically used in tuberculosis], erectile dysfunction agents (such as sildenafil), ergot derivatives, azole antifungals, macrolides [antibiotics], oral contraceptive, and methadone. Unapproved therapies, such as St. John’s Wort, can also cause negative interactions.”
Consider how frequently people are prescribed one or other (or more) of these, which interact dangerously with antiretroviral drugs.
Page 23: “Treatment failure is often associated with virologic failure, immunologic failure, and/or clinical progression…
virologic failure, immunologic failure, and clinical progression have distinct time courses and may occur independently or simultaneously. . . . These events may be separated by months to years.”.
In other words, “failure” may refer to viral load (“virologic”), CD4 counts (“immunologic”), or condition of the patient (“clinical progression”). But surely it is only the last of these that should matter. That periods of months or years may separate those three phenomena underscores what dissidents emphasize and HIV/AIDS believers try to deny, that there is indefinite or poor correlation at best between the surrogate markers themselves and between them and the health of the patient.
Page 25: “Clinical progression may not warrant a change in therapy in the setting of suppressed viremia”.
Almost incredible, isn’t it? When viremia (viral load) is being decreased, treatment should continue even if the patient is sinking. Another real-life example of what some might think a jocular fantasy, “the operation must continue, even if the patient then dies”.
Page 27: “Information on relationships between concentrations and drug-associated toxicities are [sic] sparse.”
Or, we just don’t know what a safe dosage is.
Page 28: “Lack of established therapeutic range of concentrations associated with achieving the desired therapeutic response and/or reducing the frequency of drug-associated adverse reactions”.
Or, we don’t know what the effective dosage is or what a safe dosage might be.
Pages 30-32 concern “Acute HIV infection”, an intriguing phenomenon that deserves separate consideration. Further sections of the Guidelines deal with treatment of special groups: pregnant women, adolescents, people with other concurrent medical conditions. Those are followed by many Tables, some of which deserve further discussion, as does the membership of the Panel that draws up these recommendations.