Re: Some Random Comments 29 October 2004
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Peter J Flegg,
Blackpool, UK

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Re: Re: Some Random Comments

Nick Bennett has replied to some of the points raised by Mark Bartlett, but as someone who has seen the paper in question on the long term effects of antiretroviral therapy (1), I would like to add my bit for what it is worth.

The study consisted of 41 patients who had successfully responded to HAART over 5 years. Success was undeniable, with CD4 counts rising from a median of 135/mm3 to 604/mm3 at five years. As Nick Bennett has indicated, the rise was maximal in the first 18 months at a rate of 168/year, and started to level off thereafter, rising at a rate of 38/yr. This is not really surprising – there is a limit to how high counts can rise, and to have a count that has been restored to the normal range would do most HIV patients quite nicely, thank you.

Twenty-five patients had PBM HIV-DNA quantified. Here too, there was success, with mean decrease of 0.48 log10 copies/mm3 PBMC during the first year, 0.18 log10 copies/mm3 PBMC per year during the 2nd and 3rd years, and levelling off at 0.01 log10 copies/mm3 PBMC per year thereafter. Again, as expected, with maximal effect within the first year, and sustained response subsequently.

When the authors do call into question is the strategy of persisting with life-long HAART in the face of a good response. They say: “It is more and more difficult to imagine anti-HIV treatments as life-long prescriptions, given the side effects described in the long term, such as lipodystrophy (found here in nearly 60% of patients), metabolic disturbances, a possibly increased cardiovascular risk, mitochondrial toxicity and altered quality of life. In other words, the inconvenience of a very-long-term treatment may outweigh the benefit of maintaining the CD4 cell count at a high level, considering that treatment beyond 2 to 4 years will not result in a significant further reduction of the HIV-1 DNA load. For patients with high CD4 cell values (e.g. > 400 × 106/l) after this time on HAART, would it be reasonable to consider stopping therapy when the level of HIV-1 DNA reaches its lowest plateau and then wait for the patients to meet again the criteria for treatment initiation? Trials should be designed to compare this long-term strategy of prolonged periods on and off therapy with the standard attitude of maintaining HAART and with structured treatment interruptions with a shorter time scale.”

The suggestion here is that studies of interrupted therapy are conducted to develop long term strategies for managing patients who successfully respond to HAART. There is no suggestion that HAART is in itself ineffective, merely that current risks of continuous therapy may outweigh current benefits. When the HIV-DNA levels rise, or CD4 counts drop, then the risk-benefit equation would favour resumption of treatment.

It is also important to note that current HIV regimens do not use drugs that are as harmful in terms of the side effects mentioned in this study. 90% of the patients were on indinavir, which is one of the most likely to cause lipodystrophy and metabolic disturbance. Had the authors conducted a similar study using today’s less toxic drugs, they may well have come to a different conclusion. Therapy improvements continue to occur, and in many ways this study is quite out-of date, despite only being published in January.

Mark Bartlett also mentions Roberto Giraldo. His study on ELISA testing for HIV (which has never been published in a peer-reviewed journal) is well quoted in HIV-dissident circles. However, most microbial assays require dilution to adjust for non-specific low-level antibody binding and to set appropriate specificities and sensitivities. By Giraldo’s definition, pathogens such as syphilis, borrelia, EBV, etc do not exist either, because we would all test positive for them using our undiluted blood. Some of the newer HIV assays do actually use undiluted whole blood, and are very accurate, a point consistently ignored by the “everyone tests positive for HIV” dissident lobby. It is very unfortunate that people like Giraldo, with his theories that HIV does not exist, and that AIDS is caused solely by malnutrition, exert undue influence in the wrong places, such as with the South African health minister and President Mbeki (Giraldo is still an advisor on the Presidential Panel, and conducts frequent meetings in South Africa).

Finally, Bartlett mentions the use in the USA of an AIDS case definition that uses CD4 counts in addition to clinical events. Like Canada, here in the UK we have never gone down that route. AIDS is itself a rather redundant term, but at the time the CDC revised the definition in 1993, I seem to recall the main reasoning behind it was largely a socio-political one to enable everyone who did not qualify for free therapy on Medicare or Medicaid to get treatment. Until then, a diagnosis of AIDS was a necessary pre-requisite for free drug treatment and medical care, but many ill patients did not qualify even though they were ill and had low counts, because they did not also have a clinical AIDS-defining diagnosis.

(1) Viard, Jean-Paul; Burgard, Marianne; Hubert, Jean-Baptiste; Aaron, Laurent; Rabian, Cecile; Pertuiset, Nathalie; Lourenco, Maria; Rothschild, Chantal; Rouzioux, Christine. Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level. AIDS 2004 18(1) p45-49

Competing interests: None declared