dual vs. triple regimen
Sep 29, 2002
This is a follow up email regarding a friend of mine who is taking a combination of Zidovudine and Lamivude therapy. She was put on a dual therapy after the blood work came in the following:
Total White blood cell count (WBC) = 5,900 (normal) with: 37 lymphocytes of which 69 or 1,572 are T lymphocytes, Of the T lymphocytes, 11 or 251 are CD4 cells. Viral Load 151.658 kopi RNA/ml Log 5.181.
"Firstly- I'd want to be sure that your friend is not only taking zidovudine and lamivudine (2 drug) therapy. Virtually no one would find this a suitable treatment regimen alone, though certainly would be potent components of a 3- or 4-drug regimen. So, I'd ask you to verify that she's on an additional drug. If not, please write back or ask her to ask why."
Initially I had the same question after researching about drug treatments. Why the physician prescribed a dual-NRTI regiment instead of 3-Drug Regimen? Most 3 drug regimens would supress viral load to undetectable level. I have asked my friend to ask her physician. She told me that she has secured an appointment with the doctor sometime next week. Just so that you know, she is being treated in one of the Southeast Asia's countries.
Out of curiosity...I continued my research. After scouring articles, and books...I could only find two possible explanations:
a) I stumbled upon this statement from JAMA Antiretroviral Treatment for Adult HIV Infection in 2002. Here is the exact quote," Triple-NRTI Regimens Triple-NRTI regimens have become a viable alternative as initial therapy. The largest body of evidence at present is for regimens that contain abacavir. An abacavir/zidovudine/lamivudine combination produced a decrease in viral load (to <400 copies/mL) at 48 weeks equivalent to that produced by zidovudine/lamivudine/indinavir in a placebo-controlled trial.112, 113 However, more complete viral suppression (assessed with an assay with a limit of detection of 50 copies/mL) was less likely with the 3-NRTI regimen in those patients with a pretreatment viral load above 100 000 copies/mL.112, 113 Thus, these regimens are not routinely recommended as initial treatment for patients with high viral loads (eg, >100 000 copies/mL) or with low CD4 cell counts until more data are available."
b) Based on a book I have just finished, titled "Healing HIV" by Jon D. Kaiser, M.D. page 84, 85, 86 He wrote," I often sit with my HIV+ patients who are currently on dual-RTI therapy and discuss how well they have done during the past several years. Virtually all are stable, free of medication side effects, and very pleased at how many medications options they still have at their disposal. Their list of available treatment options remains long.
Conversely, many patients in the community who have been highly aggressive with antiviral treatments from the start of this epidemic have not had stellar results. Many have exhausted their list of treatment options too quickly, or are currently dealing with serious side effects caused by an overuse of these medications (e.g., diabetes, hyperlipidemia, peripheral neuropathy, liver abnormalities, and lipodystrophy syndrome). A conservative treatment approach clearly offers many long term advantages when used to treat mild to moderate HIV disease.
When using dual-RTI therapy, I try to squeeze as much time as possible out of the initial combination of drugs (potentially 2 to 3 years) before making a change. If and when the initial 2 medications need to be discarded, the patient can switch to a new 2 or 3 drug regimen for another long run of potent viral suppression. This philosophy allows the patient with mild to moderate HIV infection to go through the list of available antiviral medications as slowly as possible, while continuing to maintain excellent health and stability. Remember this philosophy only works when an aggressive natural therapies program is used in conjunction with these medications.
In most standard physician practices, 2-drug antiviral combinations have not been found to provide long periods of potent viral suppression. They have also been several published studies that have looked at comparisons between dual versus triple antiviral regimens. They all show that 2-drug regimens provide relatively short periods of viral suppression. Our experience is completely different! I attribute this difference to the fact that we combine aggressive natural therapies programs with standard medications, and with our zealous commitment to eliminating all cofactors that can potentially stimulate HIV activities (1. Herpes Infections, 2. Intestinal parasites, 3. Unhealthy intestinal environment,4. Low protein intake, 5. Inadequate antioxidant vitamins, 6. Hormonal imbalances, 7. Substance abuse, 8. Emotional distress). These interventions support the immune system's role as a partner in suppressing HIV activity. We need to attend not only to the virus but to the immune system within each individual as well. A strong immune system can then participate fully in enhancing the effects of whichever antiviral medication program a patient is taking.
Most standard physicians have a difficult time believing the success we have had utilizing this approach. This stems in part from their lack of experience with what natural therapies can do. They are skeptical because there is shortage of published research data on the benefits of combination programs such as ours. Hopefully, this situation will change"
Now to my questions:
a) What's your professional opinion on Jon D. Kaiser, M.D's approach? b) I have bought my friend: Garlic tablets, Multi Vitamins with complete antioxidant groups, Omega 3 fish oil, Panax Ginseng, Astragalus, Echinacea, Noni juice. Right now...she is taking Noni juice, Multi Vitamins, and Omega fish oil. I told her to hold on to the other supplements until she talks to her physician, and I get your answer. I am aware of drug interactions...with PIs..but not so sure with NRTIs. Please elaborate.
Thank you so much Dr. Young for taking the time to read and answer my length questions!
Response from Dr. Young
Thanks for your lengthy and thoughtful follow up.
I did not realize that your friend was not in the US or Europe. Nevertheless, my initial comments still hold. There is considerable controversy about the best way to provide care in resource-poor settings. Yes, some therapy is better than none, but sustained therapy with virtually any dual nucleoside regimen is unlikely to result in either short- or long-term virologic suppression.
As a consequence of this, persons on a ZDV/3TC regimen alone are a great risk for developing multiple drug resistance mutations in the viral reverse transcriptase gene-- leading first to resistance to 3TC, followed by resistanct to ZDV. The later is characterized by the accumulation of mutations, called thymidine analogue mutations, that when present in more than 3 or 4, are usually associated with multi-drug resistance (ZDV, d4T, ddI, abacavir and perhaps tenofovir). You can see from this that future treatment options can be seriously impacted by this early drug use.
As for the Kaiser book; most experts would dissagree with his conclusions (I'd welcome you to ask any other of the expert forum writers). Natural therapies have never been shown or proven to improve the survival of persons with HIV-- remember that these have been available since the beginning of the epidemic. The supposition that he makes can lead to the inappropriate and sometimes dangerous misuse or underuse of life saving medications (just like the espousal of dual nucleosides). I couldn't disagree more strongly.
So, back to your friend-- I'd try to find a way to encourage the use of a three drug regimen in the very near term future. There is little data about drug-drug interactions with all of the supplements that you've listed, and you note correctly, that the NRTIs are less prone to such inteactions. While your support for the purchase of vitamins is noteworthy, I'd suspect the cost of these supplements could probably support the cost of a third HIV medication too.
Good luck. Stay in touch. -BY
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