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Understanding Lifespan
Jan 30, 2007

Dr Wohl, in your recent podcast interview, you mentioned a recent study that was done to try to find out the "cost of HIV treatment". A side effect of this study was that the study came up with an "average lifespan" number of 24.2 years based on current treatments and starting treatment around the current US guidelines of CD4~350/15%.

This seems to be in conflict with the CDC's June 2005 update. Which states that there are about 1.1 million Americans who are HIV positive (between 1 and 1.2 million). The 18,000 annual AIDS deaths would be only 1.6% of this population. This means an annual remainder of 98.4%. A simple calculation (.984^43=.50) shows that at this rate of attrition it would take about 43 years on average for the HIV positives to die from AIDS (i.e. for half of them to succumb to one of the 30 or so old diseases that are called AIDS if the patient is HIV positive).

I guess I'm finding it hard to understand the discrepancy in the two sets of numbers...

I understand that there are many many factors that go into these kind of "statistics", with the most important among these being how variable each individual person responds to the particular strain and subsequent mutations of their virus.

I also understand that many of these "lifespan" numbers are just statistical mathematics, which covers things like averages of averages, etc.

To help understand this on a more personal level, can you tell me if I'm understand the following facts correctly (understanding that each one assumes "responds well"):

1) Based on current guidelines, treatment should start (and not see "interruptions") roughly around CD4<(350/15%), especially if the VL is High (>100,000)

2) Those that have a "non-resistant" strain and maintain strict compliance with their treatment plan can HOPE to see VL become undetectable and see CD4 rise over time.

3) Those that start treatment around 350 and respond well could hope to see CD4 rise upwards of approx 500 with a few responding so well as to near the level of 800 (which is the lowest range of "normal").

4) Those that see VL not reaching undetectable are probably facing some amount of drug resistant strains of the virus in their system.

5) Those that reach undetectable VL, but don't see increases in CD4 may be experiencing a deeper level of infection of Latent HIV Reservoirs (marrow, brain, & CD4 "stem cells" that are infected) such that while not contributing new virus to the bloodstream, those long lived cells are passing HIV via normal stem cell mitosis and subsequent differentiation, meaning that the resulting "new" CD4 cells are often short lived and may not reach maturity in a beleaguered Thalamus.

6) People don't die from HIV, they die from Opportunistic Infections and basically what amounts to long term treatment toxicities. It's this one that I'm finding a degree of conflicting information around.

6a) Would it be correct to say that "Age", and thus lifespan, is predominately an effect of a cell's ability to maintain healthy mitacondria? We age because as the mitacondria in our cells replicate both oxidation as well as generational "errors in replication" result in depletion of mitacondria as well as less "healthy" mitacondria over time.

6b) So with treatment while we might maintain "near healthy" CD4 levels and undetectable VL which can prevent most OIs, there is still the combination of HIV's direct effect on cells (increased Apoptosis) which when combined with mitacondrial depletion being caused by most of today's HIV medications, will still result in shorter lifespans than might be considered "normal"?

Response from Dr. Wohl

You raise many important points. It will be difficult to answer all of your excellent questions in detail as the text of such an answer would be the basis of a nice book reviewing much of what is known about HIV infection.

As far as the article I described in the podcast, the paper presented results generated from a computer simulation of a hypothetical cohort of patients starting therapy. It is not an accounting of what is happening now to the mix of HIV+ people who are at various stages of HIV infection and HIV treatment. The 24 year estimate is to be taken with a large grain of salt. The computer can not take into account everything that influences life expectancy. It also does not incorporate major advances in HIV care that I think are inevitable.

The bottom line regarding treatment is that current HIV therapy is potent and in the majority of patients will drive the viral load to very low levels, permitting growth of the T-cells. How long this lasts depends on many factors - treatment adherence and pre-treatment drug resistance being major factors. How high the T-cell count can go is very individual but generally those starting with a T-cell count of 200+ will see increases that approach or enter into the normal range.

At present, most all people with HIV infection should start therapy before the T-cell count drops below 350. If HIV is detected at a lower count, therapy should start right away. There are data suggesting starting HIV therapy at higher T-cell counts may be even better. We will see if this translates into a tendency to initiate therapy even sooner in the course of infection - I think it might.

The causes of death among people with HIV are less and less related to opportunistic infections (in the US and Europe, at least). Liver disease, typically as a result of hepatitis, is a major cause of death as are cancers - some of which may be arguably related to immunosuppression from HIV but also from increasing age of those with HIV. Infections are a problem mostly in those with really low T-cell counts. Cardiovascular disease also accounts for some deaths among HIV+ folks, but this is also the major cause of death among people living in the US, Canada and Europe. The contribution of HIV therapy to heart disease developing among people living with HIV, so far, seems to be low.

There is more to life, and death, than mitochondria.

In short, HIV therapy is good. All the data we have so far demonstrates that HIV meds prolong life - how long we just do not know at this point. There are side effects of these meds but it looks like the side effects of HIV itself trump these and are more life-threatening to more people. Starting HIV therapy before the T-cell count declines below 350 is beneficial. Taking meds that are potent and active against the virus an individual harbors and taking them as directed reduces the risk of their failure.

I hope this helps.

DW



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