Example of thinking outside of the box: SELENIUM and HIV suppression

[Bleurberry]

[FONT=verdana, arial, helvetica, sans-serif] Suppression of Human Immunodeficiency Virus Type 1 Viral Load With Selenium Supplementation . [FONT=verdana, arial, helvetica, sans-serif] A Randomized Controlled Trial .
[FONT=verdana, arial, helvetica, sans-serif] Barry E. Hurwitz, PhD; Johanna R. Klaus, PhD; Maria M. Llabre, PhD; Alex Gonzalez, BA; Peter J. Lawrence, MS; Kevin J. Maher, PhD; Jeffrey M. Greeson, PhD; Marianna K. Baum, PhD; Gail Shor-Posner, PhD; Jay S. Skyler, MD; Neil Schneiderman, PhD .

[FONT=verdana, arial, helvetica, sans-serif] Arch Intern Med. 2007;167:148-154. .
[FONT=verdana, arial, helvetica, sans-serif] Background Despite findings that selenium supplementation may improve immune functioning, definitive evidence of its impact on human immunodeficiency virus (HIV) disease severity is lacking. .
[FONT=verdana, arial, helvetica, sans-serif]Methods High selenium yeast supplementation (200 µg/d) was evaluated in a double-blind, randomized, placebo-controlled trial. Intention-to-treat analyses assessed the effect on HIV-1 viral load and CD4 count after 9 months of treatment. Unless otherwise indicated, values are presented as mean ± SD. .
[FONT=verdana, arial, helvetica, sans-serif]Results Of the 450 HIV-1–seropositive men and women who underwent screening, 262 initiated treatment and 174 completed the 9-month follow-up assessment. Mean adherence to study treatment was good (73.0% ± 24.7%) with no related adverse events. The intention-to-treat analyses indicated that the mean change (

) in serum selenium concentration increased significantly in the selenium-treated group and not the placebo-treated group (

= 32.2 ± 24.5 vs 0.5 ± 8.8 µg/L; P<.001), and greater levels predicted decreased HIV-1 viral load (P<.02), which predicted increased CD4 count (P<.04). Findings remained significant after covarying age, sex, ethnicity, income, education, current and past cocaine and other drug use, HIV symptom classification, antiretroviral medication regimen and adherence, time since HIV diagnosis, and hepatitis C virus coinfection. Follow-up analyses evaluating treatment effectiveness indicated that the nonresponding selenium-treated subjects whose serum selenium change was less than or equal to 26.1 µg/L displayed poor treatment adherence (56.8% ± 29.8%), HIV-1 viral load elevation (

= +0.29 ± 1.1 log10 units), and decreased CD4 count (

= –25.8 ± 147.4 cells/µL). In contrast, selenium-treated subjects whose serum selenium increase was greater than 26.1 µg/L evidenced excellent treatment adherence (86.2% ± 13.0%), no change in HIV-1 viral load (

= –0.04 ± 0.7 log10 units), and an increase in CD4 count (

= +27.9 ± 150.2 cells/µL). .
[FONT=verdana, arial, helvetica, sans-serif]Conclusions Daily selenium supplementation can suppress the progression of HIV-1 viral burden and provide indirect improvement of CD4 count. The results support the use of selenium as a simple, inexpensive, and safe adjunct therapy in HIV spectrum disease. .
[FONT=verdana, arial, helvetica, sans-serif]Trial Registration isrctn.org Identifier: .

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[mshheaddoc]

moving to TIH where this is appropriate for discussion

 

[DropkickMurphy]

The results support the use of selenium as a simple, inexpensive, and safe adjunct therapy in HIV spectrum disease.

The problem is that if someone is to get the dosage wrong, selenium is a particularly nasty agent (in fact, I know several common OTC vitamin formulations removed selenium from their formulas for this reason). Do a PubMed search for "selenium toxicity" and you'll see my point. I know you have a love for alternative medicine, but we can't remember that while it might seem like a good idea in theory or in a lab, putting it in the hands of the average person isn't such a smart move. You can never afford to underestimate the stupidity and lack of reasoning ability amongst your patients.

 

[Tired]

The results support the use of selenium as a simple, inexpensive, and safe adjunct therapy in HIV spectrum disease. [/SIZE].
[FONT=verdana, arial, helvetica, sans-serif]Trial Registration isrctn.org Identifier: .

Yeah, not really. Increased survival time and decreased morbidity would support this conclusion, but the study has neither. Changes in lab values do not necessarily correlate with clinical improvements.

 

[Bleurberry]

The problem is that if someone is to get the dosage wrong, selenium is a particularly nasty agent (in fact, I know several common OTC vitamin formulations removed selenium from their formulas for this reason). Do a PubMed search for "selenium toxicity" and you'll see my point. I know you have a love for alternative medicine, but we can't remember that while it might seem like a good idea in theory or in a lab, putting it in the hands of the average person isn't such a smart move. You can never afford to underestimate the stupidity and lack of reasoning ability amongst your patients.

I keep an open mind to alternative therapies, I wouldn't say the relationship has evolved to me being in bed with alternative therapy.
Good call on selenium toxicity, but uh , well, yah, good addition to the subject.
Anyhow, I posted this because I don't think minerals, and some vitamins, should be grouped into the "alternative therapy" camp. I think it's stupid and dangerous to do so.

 

[Bleurberry]

Yeah, not really. Increased survival time and decreased morbidity would support this conclusion, but the study has neither. Changes in lab values do not necessarily correlate with clinical improvements.

Hmm, let me chew on that for awhile.

 

[McDoctor]

Yeah, not really. Increased survival time and decreased morbidity would support this conclusion, but the study has neither. Changes in lab values do not necessarily correlate with clinical improvements.

The study only went 9 months. Better CD4 counts would lead to both in a longer study. Changes in lab values do correlate with clinical improvement when you are talking about HIV and CD4 counts.

 

[McDoctor]

[FONT=verdana, arial, helvetica, sans-serif] Suppression of Human Immunodeficiency Virus Type 1 Viral Load With Selenium Supplementation . [FONT=verdana, arial, helvetica, sans-serif] A Randomized Controlled Trial .
[FONT=verdana, arial, helvetica, sans-serif] Barry E. Hurwitz, PhD; Johanna R. Klaus, PhD; Maria M. Llabre, PhD; Alex Gonzalez, BA; Peter J. Lawrence, MS; Kevin J. Maher, PhD; Jeffrey M. Greeson, PhD; Marianna K. Baum, PhD; Gail Shor-Posner, PhD; Jay S. Skyler, MD; Neil Schneiderman, PhD .

[FONT=verdana, arial, helvetica, sans-serif] Arch Intern Med. 2007;167:148-154. .
[FONT=verdana, arial, helvetica, sans-serif] Background Despite findings that selenium supplementation may improve immune functioning, definitive evidence of its impact on human immunodeficiency virus (HIV) disease severity is lacking. .
[FONT=verdana, arial, helvetica, sans-serif]Methods High selenium yeast supplementation (200 µg/d) was evaluated in a double-blind, randomized, placebo-controlled trial. Intention-to-treat analyses assessed the effect on HIV-1 viral load and CD4 count after 9 months of treatment. Unless otherwise indicated, values are presented as mean ± SD. .
[FONT=verdana, arial, helvetica, sans-serif]Results Of the 450 HIV-1–seropositive men and women who underwent screening, 262 initiated treatment and 174 completed the 9-month follow-up assessment. Mean adherence to study treatment was good (73.0% ± 24.7%) with no related adverse events. The intention-to-treat analyses indicated that the mean change (

) in serum selenium concentration increased significantly in the selenium-treated group and not the placebo-treated group (

= 32.2 ± 24.5 vs 0.5 ± 8.8 µg/L; P<.001), and greater levels predicted decreased HIV-1 viral load (P<.02), which predicted increased CD4 count (P<.04). Findings remained significant after covarying age, sex, ethnicity, income, education, current and past cocaine and other drug use, HIV symptom classification, antiretroviral medication regimen and adherence, time since HIV diagnosis, and hepatitis C virus coinfection. Follow-up analyses evaluating treatment effectiveness indicated that the nonresponding selenium-treated subjects whose serum selenium change was less than or equal to 26.1 µg/L displayed poor treatment adherence (56.8% ± 29.8%), HIV-1 viral load elevation (

= +0.29 ± 1.1 log10 units), and decreased CD4 count (

= –25.8 ± 147.4 cells/µL). In contrast, selenium-treated subjects whose serum selenium increase was greater than 26.1 µg/L evidenced excellent treatment adherence (86.2% ± 13.0%), no change in HIV-1 viral load (

= –0.04 ± 0.7 log10 units), and an increase in CD4 count (

= +27.9 ± 150.2 cells/µL). .
[FONT=verdana, arial, helvetica, sans-serif]Conclusions Daily selenium supplementation can suppress the progression of HIV-1 viral burden and provide indirect improvement of CD4 count. The results support the use of selenium as a simple, inexpensive, and safe adjunct therapy in HIV spectrum disease. .
[FONT=verdana, arial, helvetica, sans-serif]Trial Registration isrctn.org Identifier: .

I'm not sure if the better numbers is a consequence of taking selenium or if the better numbers simply reflect better adherence to antiretroviral medication in the group with high selenium levels (therefore, better medication adherence). The group of patients who didn't take the selenium, and had a lab value below 26.1 ug/ml, probably also had poor adherence to their anti-retrovirals. The authors claim they accounted for this, but don't specify how, at least not in the abstract.

Overall, I don't see the harm in supplementing HIV patients with selenium as an adjunctive treatment. This study provides some evidence that it may be helpful. Just because something is toxic in large doses doesn't mean it shouldn't be prescribed or recommended. Water is toxic in large enough doses too.

 

[Tired]

The study only went 9 months. Better CD4 counts would lead to both in a longer study. Changes in lab values do correlate with clinical improvement when you are talking about HIV and CD4 counts.

Coulda, shoulda, woulda. Sorry, but when the CD4 count difference is given as –25.8 ± 147.4 cells/µL, you're going to have to resort to a lot of hand-waving to convince anyone that this "would lead to [improvements in morbidity/mortality] in a longer study". Do the longer study, then we can talk.

And it doesn't help when the p-values are given as p<0.04 and p<0.02.

 

[McDoctor]

Coulda, shoulda, woulda. Sorry, but when the CD4 count difference is given as –25.8 ± 147.4 cells/µL, you're going to have to resort to a lot of hand-waving to convince anyone that this "would lead to [improvements in morbidity/mortality] in a longer study". Do the longer study, then we can talk.

And it doesn't help when the p-values are given as p<0.04 and p<0.02.

How long are you going to carry out a study wherein the treatment group consistently displays higher CD4 counts than the placebo? At a point, it becomes unethical. But I would say there should be a larger study.

What have you got against selenium, anyway? Its not like the authors suggest it replace standard therapy. The authors are just suggesting its a useful adjunct therapy.

I don't have a big stake it in either way. It's hard enough to get HIV patients to take their standard antiviral regimen, let alone add on an antioxidant. Not worth debating.

 

[Tired]

How long are you going to carry out a study wherein the treatment group consistently displays higher CD4 counts than the placebo? At a point, it becomes unethical. But I would say there should be a larger study.

What have you got against selenium, anyway? Its not like the authors suggest it replace standard therapy. The authors are just suggesting its a useful adjunct therapy.

I don't have a big stake it in either way. It's hard enough to get HIV patients to take their standard antiviral regimen, let alone add on an antioxidant. Not worth debating.

My understanding is that studies get terminated early based on obvious benefits/harms of study treatments. Improved lab values with marginal statistical significance wouldn't seem (to me anyway) to be a reason to kill the study. Also, no mention was made of that in the abstract, so hopefully the study is still continuing.

I have nothing against selenium. However, I do believe that all studies should be evaluated critically, and we should draw accurate conclusions based on data. Too often we make leaps from small/short studies to clinical generalizations when the data simply isn't there. The recent difficulties with non-acute stenting, HRT, and COX-2 inhibitors are, in my mind, strong evidence that we should be very careful about what we recommend to patients and why.

Sorry if I seemed worked up, I'm really not. I just think that critical evaluation of evidence is a poorly-taught skill in medicine, and I'm always quick to jump on (what I seem anyway) as overly broad conclusions with insufficient evidence.