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Ok,Mr. Dr. Al Cohen, it's Bo Bo Part II
Jan 28, 2002

Dr. Cohen: Thank you for your swift answer to my first posting. Now I have several questions for you: 1) is the window of opportunity set within six months for all HIV+ people without genetic compostion taken into consideration; 2) does lipodystrophy present itself in individuals with low fat to muscle ratio while on HAART; 3) given that PI's have severe side effects, will T20 or T1249 be utilized in place of the former in a triple combo; 4) are those who miss the window of opportunity fighting a battle that will be lost as HIV will eventually become resistant to meds; 5) do those who do not form HIV antibodies until 5 and one half months after expose more prone to rapid disease progression as opposeed to does who develop them earlier, as the virus has had longer to injure further as no immune responce had yet been mounted; 6) what role does age play in the development of HIV antibody formation; 7) how close is medicine to having viable gene therapy; 8) does the British medical establishment recommend starting HIV meds at CD4 counts of 200? 9) will I, as a 38 year old male, live to see 60 plus years with the benifits HAART and any of the drugs in the pipe line. Thanks, Dr. Cohen for your consideration of these question.

PS:My girlfriend thinks I should wait until the current CD4 baseline is reached before undergoing HAART, yet I not convinced her approch is correct,as the quality of CD4 cells generated in the presence of antivirals might be inferior to those lost. Do you concur?

Response from Dr. Cohen

Well, O bo - here goes. Lotsa follow up questions so i reposted your questions with some thoughts below them.

1) is the window of opportunity set within six months for all HIV+ people without genetic compostion taken into consideration;

This "window" period refers to the observation of how quickly T helper cells -- specifically those which are potentially competent in their ability to control HIV -- might be lost in the period after initial infection. And six months is as you might predict an estimate, not an absolute. Since some emerge from that initial period with these cells intact - for years after. However, in several studies, it is less likely to find these cells sometime after six months. But they may be there for some people after that point. And for others, they may be gone sooner. There are few predictors yet who is in what group -although at some future time, genetic testing may allow us to better know who is able to control HIV without meds -- but that day is still in the future.

2) does lipodystrophy present itself in individuals with low fat to muscle ratio while on HAART;

Yes - Lipodystrophy can present in anyone who starts on HAART / combination antivirals after a time. As a generalization again, those who are lean to begin with may have more obvious signs of fat loss show up first - this may occur in the upper arms, the thighs, and the face. But being lean does not protect against fat accumulation in the belly - it just may take longer to see it. Nonetheless, one generalization is that men seem to be more prone to the fat loss, while women note more fat gain. But there are exceptions to both.

3) given that PI's have severe side effects, will T20 or T1249 be utilized in place of the former in a triple combo;

Since T20/1249 are given by self injection under the skin, it is expected that these will be reserved for use only when there are not enough "pills" to create an effective combo. But it is certainly possible that if these newer antivirals do not have any impact on body shape nor other problems, they could potentially be used as a substitution for another effective drug to minimize side effects. By the way, you mention specifically protease inhibitor side effects, but clearly any and all of these meds can have problems -- including for example body shape changes which we now understand to be a result of both the protease inhibitors and the nucleoside RT inhibitors.

4) are those who miss the window of opportunity fighting a battle that will be lost as HIV will eventually become resistant to meds;

I am not sure which window you refer to here - but even for people who start meds after month 6 (the window in question #1) or who start antivirals with low T4 cells (the treatment guideline "window") we can often create successful combinations that don't lead to resistance. Resistance to meds can often be avoided - it is a partnership between picking active medications that are potent enough for that person's viral load/T4 count, and then are taken each day each dose as needed. There are some drug interactions that may also lower the blood levels of these antivirals - for example, St Johns Wort and indinavir - but for now these appear to be infrequent at best. When we pick meds that people take - resistance is a rare event.

5) are those who do not form HIV antibodies until 5 and one half months after exposure more prone to rapid disease progression as opposed to does who develop them earlier, as the virus has had longer to injure further as no immune response had yet been mounted;

For now there is little clear role that antibodies play in slowing down the damage from HIV. There may be one - but the role of our cellular immunity seems more important. And in those with an ineffective immune response of whatever type - yes more damage can occur after infection. These may be the people who suffer immune damage more quickly and therefore need the help of meds sooner.

6) what role does age play in the development of HIV antibody formation;

No clear role in age and antibodies - we see them from birth to death.

7) how close is medicine to having viable gene therapy;

Well, if you mean gene therapy to treat HIV - this is still far away - with few if any important candidates in testing. This was the focus of research for years but to date there have been no successful advances that I am aware of.

8) does the British medical establishment recommend starting HIV meds at CD4 counts of 200?

Not sure why you specifically ask about the Brits - but in generally, all guideline panels have agreed that starting HIV meds above a Cd4 count of 200 is best -- since those who have started with counts below this seem to still have a higher rate of illness than those who started treatment above these counts. But none of the guidelines suggest that you SHOULD wait until 200 - they all say that treatment should be above 200 - how high above 200 cells is the point of much ongoing discussion and debate... and research.

9) will I, as a 38 year old male, live to see 60 plus years with the benefits HAART and any of the drugs in the pipe line.

Well - needless to say, I can't predict the future quite that well. Things happen to people and there are unexpected surprises. People smoke, have high cholesterol, and have heart attacks in their 40's and 50's who are HIV negative for example. Also, I don't know why you'd pick 60 as the minimum goal -- planning for when to pull your retirement accounts perhaps?

However I can say this - which is that the advances of HIV treatment are sufficient to expect that when all goes right, the lifespan of someone with HIV infection may be similar to those who are HIV negative. There may be twists and turns we don't see yet - but living 22 more years is certainly a very reasonable expectation based on everything we now know how to do.

PS:My girlfriend thinks I should wait until the current CD4 baseline is reached before undergoing HAART, yet I am not convinced her approch is correct,as the quality of CD4 cells generated in the presence of antivirals might be inferior to those lost. Do you concur?

As for the quality of the Cd4 cells that regenerate on treatment - it is remarkable just how competent these cells are. People who once had CMV infection and then regrow their T4 counts can stop CMV treatment. Most people in fact have been able to enjoy the benefits of these regenerated cells - and stop the treatments needed because of illnesses that occur only at lower counts. Whether there are remaining gaps - it remains a concern and there indeed may be some. And in years from now we may understand this better - but if there are gaps, people can remain remarkably well despite whatever these gaps may be... However, that does not mean it is better to wait until these gaps occur - just that we can do remarkably well if they did occur. The decision of when to start is made by each person weighing the pros, and cons, of treatment now versus delaying, as you apparently are.

As for the gap between you and your girlfriend in when to start treatment, I can only provide info. You need to work out the translation of options and advice into your plan. And good luck!

PS to paraphase Paul Simon, you can call me Al, though the name's Cal...



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