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Transcript of The Body's Live Chat on Multidrug Resistance With Nelson Vergel

July 10, 2006

Nelson Vergel, B.S.Ch.E., M.B.A.
Following is the transcript of The Body's live chat on multidrug resistance, which took place on July 10, 2006, at 3:30 p.m. Eastern Time. The chat was moderated by The Body's editorial staff and hosted by HIV treatment advocate Nelson Vergel. This transcript has been edited for grammar and clarity. Additional follow-up information was obtained from the host after the chat's conclusion.

This is the seventh chat that The Body has moderated; to see transcripts of previous chats, click here.

Moderator: Thank you for coming to The Body's live, interactive chat on HIV treatment issues for people with multidrug resistance. We're about to get things started! A quick note before we get going: Please keep in mind that the information we provide in this chat is not meant to replace the attention or advice of a doctor or another health care professional. Make sure you consult with a qualified health care professional before making any dietary, drug, exercise or other lifestyle change!

Nelson, before we begin answering everyone's questions, why don't you take a few minutes to tell folks a bit about yourself?

Nelson Vergel: My name is Nelson Vergel. I have been positive for 23 years. Until recently, I have never had an undetectable viral load. I have been a victim of sequential (or virtual) monotherapy (adding a new agent to a failing regimen). I started AZT [brand name: Retrovir; also known generically as zidovudine] as monotherapy in the late 1980s. Treatment with individual nucleosides followed, and I subsequently developed resistance to each of them. [I was started on] saquinavir [brand names: Fortovase, Invirase] treatment in 1996, but due to its low absorption in my body, I developed resistance to it and to most protease inhibitors.

I tried Viramune [generic name: nevirapine] and Sustiva [generic name: efavirenz; also known by the brand name Stocrin] and also developed resistance to them pretty quickly. Next, I tried Kaletra [generic name: lopinavir/ritonavir] in combination with Invirase; this stabilized my CD4 cells in the 500 range for a few years. After 2002, my CD4 cells declined gradually while my viral load stayed in the 20,000-60,000 range, even with mega-HAART regimens (more than four drugs). I then started Fuzeon [generic name: enfuvirtide; also known as T-20] on top of my failing regimen, and it stabilized me for two years more.

Two months ago, my CD4 cells had dropped to 180 and my viral load was around 40,000. I joined the Merck integrase study and started Prezista [generic name: darunavir; also known as TMC114] and kept Viread [generic name: tenofovir] and Combivir [generic name: zidovudine/lamivudine; also known as AZT/3TC] in my background therapy. My viral load now is undetectable for the first time and my CD4s have gone up to 260. I am excited and hopeful.

I have been an HIV treatment activist since 1988. I have also been lucky to be part of the AIDS Treatment Activists Coalition. This has given me the opportunity to interact with pharmaceutical companies, researchers, the FDA [U.S. Food and Drug Administration], and key activists to learn a lot about drug development and give input into research studies. I am the founder of salvagetherapies.org, facialwasting.org, medibolics.com, and the largest HIV discussion group on the Internet (PozHealth at Yahoo.com). I am also the co-author of the book "Built to Survive." My main goal, currently, is to educate HIV-positive people living with multidrug resistance about current and future options, so that they avoid adding a single new active drug to a failing regimen, as this does not maximize their long-term chances for viral control and survival. For more information about my non-profit organization, PoWeR (Program for Wellness Restoration), go to powerusa.org.

Moderator: Thanks, Nelson -- and congrats on your successful new med regimen! Let's start the chat! Please feel free to submit any questions you have for today's speaker: Nelson Vergel, a leading patient advocate in the field of multidrug resistance.

Question from anonymous: Nelson thanks a lot for sharing your knowledge with us. I have nothing left that works for me. I took Fuzeon for eight months, but it stopped working. My T cells are 60 and my viral load is 80,000. My doctor wants me to start the new drug Prezista and start Fuzeon again. I am not sure what to do. What would you do, if you were me?

Answer from Nelson Vergel: I am sorry that you are going through the stress of trying to find new options to control your HIV. Luckily, we are about to have a few more options than [we have had] in the past few years. I would suggest that you talk to your doctor about running a genotype test for Fuzeon to see if there is still any activity to it for you. But chances are that you may already have resistance to it. Some clinicians also may argue that even if sensitivity to Fuzeon shows in your genotype test, it may actually be a case of "archived resistance" that may reemerge pretty quickly after you restart Fuzeon.

Luckily, we may have three new medications (Merck's integrase inhibitor [MK-0518], Tibotec's non-nucleoside TMC125 [generic name: etravirine], and Pfizer's maraviroc [also known as UK-427,857], a CCR5 entry inhibitor) in expanded access in the next few months that we can use to avoid "virtual monotherapy" and to give us the luxury of starting two to three new agents at the same time. There are also two other products coming up in phase III studies soon: Gilead's integrase inhibitor [GS 9137] and Tanox's TNX-355 (an IV [intravenous] that will be administered every two weeks). These two phase III studies also will provide options with which to combine Prezista and/or Fuzeon. I hope that Merck, Tibotec, and Pfizer will work together to allow the use of their drugs in each other's expanded access. This will be the first time in HIV history that we will have the luxury of three agents being available close to each other.

Your doctor will be able to help you determine if you should stay on a "holding pattern regimen" until you can start at least two new agents. It is a very difficult decision that needs to weigh your current symptoms and past CD4-decline trend.

Moderator: You can learn a bit more about Merck's integrase inhibitor MK-0518 by visiting: www.thebody.com/treat/mk0518.html.

Question from swhoutx025: Will I develop drug resistance even if I am vigilant and adherent to my current HAART therapy (Sustiva + Truvada [generic name: tenofovir/emtricitabine; also known as TDF/FTC])?

Answer from Nelson Vergel: In my 10 years of lecturing around the country, I have met many people who have been on their first regimen for many years. There is no reason why you should not be successful at keeping your viral load undetectable for a long time, if you are adherent to your meds.

Question from anonymous: Nelson, I hear that there is an oral Fuzeon coming out. Is that true and when? What new drugs are coming out in the next year? I have run out of everything and my T cells are low, but my doctor tells me to be patient.

Answer from Nelson Vergel: No, not really. Roche is investigating injectable fusion inhibitors that may be administered once a week, but this work is in very preliminary stages. Some people may confuse the oral CCR5 entry inhibitor class with fusion inhibitors, however. The medical and treatment advocacy community is anxiously waiting to see data from Pfizer's maraviroc study in treatment-experienced patients in the next few months. Maraviroc is an oral entry inhibitor that may work as an "add-on" to HAART in patients with multidrug resistance.

Question from anonymous: Nelson, I have resistance to all medications, including Fuzeon. My T cells are only 5 and my viral load is 80,000. I am very afraid of having a flare-up of my old CMV [cytomegalovirus]. I have a good doctor [who is up-to-date] with all the studies for salvage. He has offered to enter me in the DUET study of TMC125 or the Merck integrase study. I do not know what to do. I want to survive and get better. Do you know anything about these studies? Should I join or do something else?

Answer from Nelson Vergel: I am sorry that you are going through such a stressful dilemma. But, in a way, think about how many options you have now that you did not have just a few months ago! Tibotec's DUET studies (DUET 1 and 2) are being conducted in the hopes to get a new non-nuke, TMC125, approved. Fifty percent of patients will be randomized to ritonavir [brand name: Norvir]-boosted TMC114 + TMC125 + nukes with or without Fuzeon; the other 50 percent of patients will be enrolled in ritonavir-boosted TMC114 + placebo TMC125 + nukes with or without Fuzeon.

Since you have resistance to both nukes and Fuzeon, you may be exposed to only one "active" agent (TMC114) in the placebo arm. Tibotec will rollover anyone who does not have virologic control in the placebo arm at month six to open-label TMC125. From data in POWER 1 and 2 (the studies that got Prezista approved), we know that around 18 percent of patients with no active agents left achieved an undetectable viral load at week 24 with Prezista (this may or may not be similar to the response we may see in the DUET placebo arm).

For those with very low CD4 cells, declining health, and no active agents left, Tibotec may provide TMC125 in an emergency IND (Investigational New Drug) program [which doctors can use to get access to an investigational drug] depending on the patient's clinical picture. This way, you may be able to construct a two-active drug regimen with Prezista + TMC125. However, your doctor has to justify to the company that you are not a good candidate for DUET due to your health and the risk of virtual monotherapy in the placebo arm. It is not a simple process since they have to agree to give you the drug, get your doctor to fill out two forms for the FDA, and get your doctor to get local IRB (institutional review board) approval for your application. More details on this is available at salvagetherapies.org.

In the Merck integrase study (BENCHMRK study to get MK-0518 approved), you have a 33 percent chance of being randomized to placebo MK-0518. Merck will rollover those in the placebo arm to treatment at week 16 if no virologic control is attained. You can use Prezista, nukes, non-nukes, and Fuzeon in this study. This study may be closed to enrollment soon since it has accrued really fast. We are hopeful that Merck will provide this drug in expanded access before the end of this year, which may give people an opportunity to construct a regimen with more than one active agent. Regimens like Prezista + MK-0518 + TMC 125 + nukes with or without Fuzeon will be a reality in the near future.

Moderator: The DUET studies that Nelson referred to are currently enrolling multidrug-resistant HIVers in the United States and several other countries. To learn more about these trials, visit: www.clinicaltrials.gov/ct/show/NCT00255099 and www.clinicaltrials.gov/ct/show/NCT00254046 (each trial has different testing sites, so check each one to see if it has a site near where you live or work).

[As of mid-July 2006, the DUET studies are almost fully enrolled. Tibotec will be providing TMC125 in expanded access in a few months.]

Question from anonymous: Do you know much about the new "black box" warning that Aptivus [generic name: tipranavir] can cause "intracranial hemorrhage" or something like that? What does it mean, and should I be worried about it?

Answer from Nelson Vergel: The maker of Aptivus has reported 14 cases of intracranial hemorrhage events, including eight fatalities, in 6,840 HIV-1-infected individuals receiving Aptivus capsules in combination antiretroviral therapy in clinical trials (0.2 percent of all patients in the study). Many of the patients who experienced this problem had other medical conditions -- CNS [central nervous system] lesions, head trauma, recent neurosurgery, coagulopathy (when bleeding following an injury is prolonged and excessive), hypertension or alcohol abuse -- or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events. It also seems that this problem had been observed before in people with advanced disease taking other protease inhibitors in the past.

Boehringer Ingelheim is investigating this problem right now in more detail. Physicians have been informed to closely monitor patients who may have any of the risks factors mentioned. Aptivus is a protease inhibitor that has helped many patients with multiple protease resistance. Those who are benefiting from it should discuss this new information with their physicians, especially if they have any of the risks factors mentioned above. We will know more details about this in a few weeks, hopefully.

Moderator: You can read more about the tipranavir "black box" warning at: www.thebody.com/kaiser/2006/jul3_06/aptivus_warning.html.

Question from Dora: I was wondering if you read Rob Camp's analysis of TMC114 for Treatment Action Group. He intimated that we still know so little about TMC114. Doesn't this scare you? I mean the report last week about tipranavir's weird and dangerous side effect of intracranial hemorrhaging sure scared me. Who knows what we don't know about TMC114. What do you think?

Answer from Nelson Vergel: TMC114 was approved with fewer than 500 patients in a controlled setting. It seems to be an effective drug for multidrug-resistant patients with a good side-effect profile so far, but we need to be cautious since the sample size is a lot smaller than that of previously approved drugs. Only time will tell what the "real-world" side effects of this drug are. Hopefully, we will see 48-week data soon.

Moderator: For more news and info about TMC114, check out: www.thebody.com/treat/tmc114.html.

Question from tigerguy: Is it OK to drink alcohol in modest amounts while on HAART or can this result in aberrant blood levels of one's HAART meds and consequently lead to drug resistance?

Answer from Nelson Vergel: It depends on what you call modest amounts. As you know, HAART can burden the liver in some patients; so drinking alcohol in large amounts may worsen this problem. Alcohol in moderate amounts (one to two drinks per day) may actually improve good cholesterol levels. So, moderation is key.

Question from anonymous: I developed resistance to nevirapine + lamivudine [brand name: Epivir; also known as 3TC] + stavudine [brand name: Zerit; also known as d4T] after over three years, so my doctor decided to add abacavir [brand name: Ziagen] to my regimen. My viral load became undetectable, but how long will it take before I develop resistance to the new combination? And is there any particular cause for the resistance?

Answer from Nelson Vergel: Your doctor "intensified" your regimen with one new drug combined with a failing regimen. It is very difficult to assess how long intensification can sustain viral load control. We are walking away from the intensification philosophy and focusing more on starting at least two active medications at the same time after resistance to a regimen occurs. Hopefully, you still have the protease, integrase and entry inhibitor classes available for you, if you do develop resistance to this regimen. I will caution you to discuss with your doctor the potential risks of stavudine for lipoatrophy and neuropathy.

Question from lalaland: In your view, is poor adherence the biggest factor in the development of resistance? Can you discuss other causes?

Answer from Nelson Vergel: Yes, poor adherence may be one of the main factors that predispose somebody's virus to develop resistance. However, poor absorption, liver metabolism, race and gender factors, body weight, medication history and pre-existing resistance, sub-optimal dosing and drug interactions may also cause blood levels of medications to be suboptimal. I know many people who had great adherence and then developed resistance in a few months. We need to be careful not to always try to find fault in the patient when resistance develops.

Question from anonymous: I read in the newspaper that a new pill is being approved this week that is an entire regimen in and of itself; it's Truvada and Sustiva combined. My question is: What's the big deal about this, if it's just a combination of two drugs we already use? Is the only difference that I'd be taking one less pill a day? Same side effects and everything?

Answer from Nelson Vergel: This is great news for people who are naive to medications and who are afraid of taking pills. However, for most of us in this chat room that have multidrug resistance, this new one-pill-a-day option provides little benefit. I hope the two companies collaborating on this formulation do the right thing and provide this pill at low cost to ADAP [AIDS Drug Assistance Program], Medicare/Medicaid and developing countries. Issues with one of the components (Sustiva) and its use in people with a history of depression and in women of childbearing years should also be clearly explained to potential users of this convenient pill. Also, skipping doses of a three-drug pill may predispose someone to resistance in a faster way, so good adherence education must be provided.

Question from anonymous: My boyfriend will start a new regimen of only Fuzeon and TMC114 (Prezista) boosted with Norvir in two weeks. His T cells are around 45. He has done different resistance tests in the past and has come up resistant to everything at one time or another. His doctor said it is useless to give him any other meds since he has already shown resistance to everything. Using only two meds instead of three doesn't sound potent enough to me. Here in Italy, the clinic doesn't want to do another resistance test (too expensive and useless they say). Also, he was told that the new integrase inhibitor isn't available yet in Italy. What should he do -- take nothing and wait for three new drugs or take the two new drugs and hope for the best?

Answer from Nelson Vergel: For many people in multidrug resistance, salvage situations like this, starting at least two new agents has shown to be more effective than starting one new agent on top of a failing regimen. The benefits of waiting for a third agent that may provide an even better response should be measured against the probability of death or illness at the CD4 levels that your boyfriend has. Also, we may benefit from drugs to which our virus has developed resistance. For instance, I am using Combivir and Viread as a background even though I have resistance to them. Nucleosides have shown some benefits in decreasing the replicating capacity of the virus even in people with multidrug resistance.

Two new agents will be available in a few months in the U.S. and possibly Europe. The Merck integrase inhibitor and TMC125 (a non-nuke) may be available in expanded access in a few months. Your boyfriend should talk to his doctor about this numbers' "waiting dilemma" to assess the pros and cons of starting two active agents now or waiting for three in a few months. Another unknown for most of us now is: How much will intensification with the integrase class benefit those who have not fully suppressed their virus on options like Prezista + Fuzeon?

Question from tigerguy: How often does HIV genotype testing need to be performed to assess for newly developed resistance? Before ever starting on HAART I had this testing done and had one mutation to the Sustiva class of drugs [NNRTIs]. Also, can drug levels themselves be monitored to assess for individual differences in drug metabolism?

Answer from Nelson Vergel: Many physicians nowadays are performing genotype tests in treatment-naive patients to find out if there is any preexisting transmitted resistance like in your case. Some studies have shown that up to 14 percent of people who are newly diagnosed may have preexisting resistance inherited from the person who infected them. So, first-line regimens may not work as well for them. After a patient reaches an undetectable viral load, there is no need for resistance testing. In my case, I have gotten genotype tests before starting a new regimen.

There is no consensus among clinicians in the United States about the clinical significance of therapeutic drug monitoring [TDM]. In some European countries, TDM seems to be more accepted as a means of assessing medication blood levels in people who are experiencing side effects or drug resistance if using protease inhibitors or non-nucleosides. The ACTG [AIDS Clinical Trials Group] is currently performing a study on TDM.

Moderator: More on this study can be found at: http://clinicaltrials.gov/ct/show/NCT00041769.

Question from Ted: How did you find a good HIV specialist? I mean, do you figure out your regimen yourself or do you have some doc that you really trust?

Answer from Nelson Vergel: The best way to find a good HIV doctor is to ask people online, support groups, nonprofit AIDS service organizations, etc. [check out The Body's extensive list of AIDS organizations around the world]. Once you set up the first appointment, it is your duty to ask the doctor basic questions about his philosophy and approach to treating not only HIV but also side effects related to HAART. I'm lucky to have a very experienced and progressive doctor who not only embraces pharmaceutical treatment but also complimentary therapies. However, it is up to you to keep up-to-date with information since most doctors are extremely busy. Keep in mind that your doctor's support staff is sometimes as important as the level of experience and "bedside manners" that the doctor may have. I know great doctors with poorly trained support staff that make office visits and follow-ups a nightmare.

Question from anonymous: I would like to know your feeling about natural treatments. Have you ever tried them?

Answer from Nelson Vergel: I am a Latino man from South America, where our culture tends to be a lot more inclined to use herbs and natural therapies. However, after living with HIV for 23 years and using many products, I have developed a strong bias against unproven therapies for HIV control. I have also seen friends die because they only embraced natural therapies. I believe these therapies are complementary to HIV meds, not alternatives. However, I am a strong believer in the evidence of micronutrients, exercise, meditation, and good nutrition in maintaining health while living with HIV. Another thing that concerns me about some herbal products is the potential interaction with HIV medications (like the case of St. John's wort and Crixivan [generic name: indinavir]). [For more on drug interactions, click here.]

Question from anonymous: Have you heard of apple cider vinegar as an alternative treatment for HIV?

Answer from Nelson Vergel: Yes and all those claims are not based on any research or evidence. I would stay away from this. I am afraid that some people may be fooling themselves with stuff like this and not facing the fact that HIV medications may help them. I would also suggest you check with buyers clubs like the one in Houston [Houston Buyers Club] or New York [New York Buyers' Club] for more information on supplements and complementary therapies. They keep up with published data and try to only buy from companies with good quality control. Remember that the FDA does not regulate the supplement industry (and neither do we want them to).

Moderator: The Body has more info on complementary therapies at: www.thebody.com/dietnut/vitamins.html.

Question from Corey: Which micronutrients do you take and what evidence do you have that there are no interactions between them and your current meds?

Answer from Nelson Vergel: I take selenium as an important antioxidant shown to be deficient in people with HIV, carnitine and coenzyme Q10 for mitochondrial and nerve cell protection, and a potent multivitamin like SuperNutrition's Optipak. Unfortunately, we may never see interaction studies between most of the supplements and HIV medications. So, in a way, I am taking a calculated risk based on the potential benefits that these supplements have shown in several small HIV-related studies. I have never had high lipids, neuropathy, little lipodystrophy and other side effects common in HIV-positive people taking HIV meds. Whether this is due to my supplements or not is yet to be proven, but I have a strong believe that they may have helped. However, I caution everybody to talk to their doctor about any supplements that they are considering taking. Do not fall for the next scam or trend. Ask around and do research before spending your money and putting too much faith in claims that are not even backed with pilot studies. Both Tufts University and University of Miami have published good studies on micronutrients and HIV.

Question from anonymous: I am a 47-year-old female who has had HIV for about 15 years now. My first round of HIV drugs caused me to come down with lipodystrophy, and the pain in my legs at times can be unbearable. I've been on several series of Serostim [a brand of human growth hormone] and they have all helped, along with exercise. But this last time seems to be much harder on me for some reason. Is this normal? Why can't I just take Serostim indefinitely? Also, I read that oxandrolone [brand name: Oxandrin; an oral anabolic steroid] can restore muscle and fat tissue. Is this true, or will I have fat loss in my legs and butt forever? Would this anabolic steroid make my stomach even bigger?

Answer from Nelson Vergel: I am sorry that you are battling body changes like many of us have. Serostim has been shown to be effective at reducing internal abdominal fat, but it is very expensive, not approved for lipodystrophy yet, can cause joint pains and diabetes in some, and requires injections daily or two to three times a week. It can also cause a decrease in subcutaneous fat (lipoatrophy). But at lower doses of under 2 to 3 mg a day, it seems that many can tolerate it. Anabolic steroids like Nandrolone and Oxandrin can increase strength and lean body mass in HIV-positive men and women. But they can disrupt your hormonal balance, so they need to be administered by a doctor who has some experience with them and HIV-positive people. Anabolic steroids have not been shown to decrease visceral fat by much, and they may decrease subcutaneous fat. I have had good experience with them. I think they may help us compensate for the loss of fat mass in the limbs by increasing lean body mass there. Some of us may also have a muscular "steroid belly" due to increases in muscle and organ tissue in that area.

I think cardiovascular exercise and limiting your simple carbohydrate intake may show more promise in decreasing belly fat than anything else out there. But both options require commitment and adherence, two things that are difficult for many people. Avoiding certain HIV meds like Zerit and others that may cause insulin resistance may be something to consider.

I wish that some company would be interested in researching buttock restoration. Many people I talk to in my lectures have difficulty sitting for long periods of time due to extreme loss of tissue in their buttocks. Patients with money are flying to Mexico and Brazil to get their butts restored with unknown long-term risks.

Moderator: You can learn much more about body-fat changes and related health problems by visiting: www.thebody.com/treat/lipodystrophy.html.

Question from anonymous: My husband is HIV positive. He has responded to all of his meds and has lived well with the virus for over 14 years. [However,] we were told that there was nothing left. He has been off meds since November 2005 with a promise from the doctor -- first in January, then March, and now again in July -- that a new drug will be available. I don't know how much longer he can wait. I am scared. He has lost so much weight, [he has] nose bleeds, [his] mental health is poor, and [his] memory is failing. I called today and spoke with the doctor's office, which said that TMC114 won't be available until August [TMC114 was approved on June 23, 2006]. What should we do? I have given up my job to be with him through this period. I don't want to give up hope.

Answer from Nelson Vergel: I'm assuming that your husband developed resistance to all available medications, including Fuzeon. A new protease inhibitor (Prezista) has recently been approved for people with multi-protease inhibitor resistance [for information on this new drug, click here]. There is also an integrase inhibitor (MK-0518) and a non-nucleoside (TMC125) that should be available in expanded access in the next few months. Prezista plus these other drugs may provide a lot of hope for people like your husband. Also, people living with multiple drug resistance and declining CD4 cells and health should not be on long treatment interruptions. Dr. Deeks in San Francisco has shown that staying on simple nucleosides like Epivir on their own (called "partial treatment interruption") slows down the rate of CD4 cell decline and viral load increase in people living with multidrug resistance.

If you feel like your husband's doctor is not being aggressive enough about his treatment options, you may want to ask around to find another doctor who may have more access to research protocols and expanded access programs.

Question from anonymous: Why is it that I have been undetectable for three years already and my CD4 has only gone up a little? When I was diagnosed, my CD4 was 40; in February 2006 it went up to 74, but in May it went down to 62. Can you tell me what is going on, or maybe try to help me with what I can do to boost my CD4 count? My CD4 percentage is 7 percent.

Answer from Nelson Vergel: This is one of those puzzling questions. Some people have very small increases in CD4 cells with HAART. I am not sure how long you have been on HAART, though, and what meds you are taking. Sometimes it takes a long time to see small increases in CD4 cells. There is no consensus in the medical field whether the use of Interleukin-2 [generic name: aldesleukin; brand name: Proleukin; also known as IL-2, r-serHulL] in patients like you will have long-term benefits, but this is something that you may want to talk to your doctor about.

Moderator: Our site has a bit more info about Interleukin at: www.thebody.com/treat/interleu.html.

Question from anonymous: [I am] a newly diagnosed HIV-positive individual. Do you think that [via] constant changing of therapies [I can] prevent long-term toxicities? In essence, what I am asking is, should we constantly be changing up our regimens to keep the virus at bay, or do you think that doing so will cause future multidrug resistance? I do not know if any studies have been done to see whether this can be done.

Answer from Nelson Vergel: The key to success in treating our HIV is to find the best possible combination that will provide the longest and most sustainable response with the fewest side effects. With over 22 treatment options right now, we have more options to do so. After 10 years of HAART, clinicians have learned to choose the most effective and least toxic regimens. There has been very little research in sequencing and alternating different regimens to prevent long-term toxicities while sustaining viral replication control.

Moderator: I'm afraid we only have time to answer one more question; my apologies again to everybody who submitted excellent questions that we couldn't get to today! I hope you'll consider using The Body's "Ask the Experts" area at www.thebody.com/experts.shtml to get the answers to your questions.

You can also join Nelson's discussion group for HIVers by sending a blank e-mail to pozhealth-subscribe@yahoogroups.com.

Question from tigerguy: What is the typical length a given regimen will be effective before resistance is developed to at least one of the drugs, assuming 100 percent compliance with the prescribed regimen?

Answer from Nelson Vergel: There is no way to predict length of response in patients. For instance, long-term follow-up studies on the use of Kaletra have shown that many people on this drug still have an undetectable viral load after five years. For those with no resistance at baseline, this is an achievable reality. We definitely need long-term studies on this question.

Moderator: Our interactive chat on multidrug resistance has now ended. Nelson, thanks so much for taking the time to answer everyone's questions!

Nelson Vergel: I want to thank TheBody.com for giving me the opportunity to volunteer to share my experience with my fellow HIVers and thank all of you who have taken the time to be in this chat. There are lots of good things happening for us patients living with multidrug resistance. Stay tuned!!

Moderator: The pleasure's all ours, Nelson. :)Thank you all again. Have a good evening!


Post-Chat Questions

These questions were submitted before or during the chat, but, because of time limitations, Nelson did not have the chance to answer them before the live chat concluded.

Question: I am very allergic to even small doses of Norvir. I get horrible diarrhea, fatigue and bloating even with 100 mg a day of Norvir boosting in protease regimens. The new drugs Aptivus and Prezista require Norvir boosting. Please, please, tell me that there are drugs coming up that do not require Norvir.

Answer from Nelson Vergel: There is good news for you. There are three drugs currently in development that do not require Norvir. They are MK-0518, the Merck integrase inhibitor; TMC125, Tibotec's second generation non-nucleoside; and maraviroc (a CCR5 entry inhibitor). All of them may be available in the next few months in expanded access programs. I hope those three companies are looking ahead to allow the use of each other's investigational agents (as long as they show no potentially negative interactions).

Question from anonymous: My 14-year-old has multidrug resistance, even to drugs he has never taken. Genotype testing revealed that he has intermediate resistance to amprenavir [brand name: Agenerase] and tipranavir. He has been on treatment since age four and I can assure you that I have faithfully given him his meds as prescribed all the time. I can't access new drugs, but if I did what would I combine with them? Rescriptor [generic name: delavirdine] is the only other drug that he can respond to, but I have read some not so encouraging news about it. I am going out of my head with worry.

Answer from Nelson Vergel: I am assuming you live in the U.S. or Europe. It must be very stressful for you to have to worry about your son's health. You may want to talk to his doctor about how to construct a "holding regimen" with the few drugs that his genotype shows some sensitivity to, or about how to start him on new drugs like Prezista and Fuzeon, or about waiting for the integrase class to be available in a few months in expanded access or in a phase III study.

Question from anonymous: I am a clinician providing care and counseling for PLWHA [People Living With HIV/AIDS] in Uganda. This is a resource poor setting. Clinical assessment may not be enough to confirm multidrug resistance [MDR] in people on treatment. What other options can I use in order to confirm MDR in such a setting where sophisticated tests are just a mere dream?

Answer from Nelson Vergel: Measuring resistance in resource-limited locations is a problem. Assuming that adherence is not an issue, previous treatment history and a viral load increase may be the only way to "assume" drug resistance. Another huge issue is what treatment options patients have available in those settings after developing resistance to first- or second-line regimens. I would suggest that you post this very important question at TheBody.com's "Ask the Experts" forums.

Question from anonymous: I participated in your seminar in Chicago for HIV-positive gay men and I'm a big fan. My question is about neuropathy or that chronic "pins and needles" feeling I get in my right leg. I've been positive for four years and it's been with me since infection. My doctor is not very "on it" and I suppose I should seek out a neurologist, but I wondered in your experience if you found something effective or [know of] something new on the horizon I could seek out.

Answer from Nelson Vergel: Thanks. I love what I do! Neuropathy is one of those things that did not get better with HAART. Some people developed it after using d4T, ddI [brand name: Videx; also known generically as didanosine] or ddC [brand name: Hivid; also known generically as zalcitabine]; others can only attribute it to HIV. I would suggest that you do go to a neurologist who has experience in HIV-related neuropathy. We do not have a treatment specifically approved for this problem. Many doctors prescribe pain and anti-seizure medications to manage it. There is some growing research in the use of carnitine, an over-the-counter supplement, to improve nerve function [Dr. Keith Henry responded to a reader's question about these studies here].

Question from anonymous: I tested HIV positive in May 2006. Currently, I am not on any meds. I still feel okay, but don't know for how long. Should I wait until I am feeling ill, or is now the right time to visit my doctor for advice?

Answer from Nelson Vergel: You should see a doctor to see what your CD4 count and viral load are. That would help you and him/her determine if you should wait or start now with medications. Do not assume that since you feel OK, your numbers are good. Some people feel "OK" with low CD4 cells and others feel lousy with high ones, so it is hard to predict if you need treatment based on how you feel. There are many good once-a-day options with low pill counts. Soon we will have a one-pill-a-day option for people who do not have resistance to any medications [Atripla approved July 12, 2006].


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