FIAR collaborates on ViraPhyte (Spring Break) study! Please note that the NCCAM grant utilized for the work in India (described below) was redirected to the ViraPhyte Project. Similar capacity development, intellectual property right issues, clinical trial design training and other related issues have been undertaken.
Gandeepam, FIAR, Mount Sinai 2-Year Planning Grant. This is a 2-year planning grant provided by the National Center for Complementary and Alternative Medicine (NCCAM) of the NIH to assist in the development of the clinical evaluation of Gandeepam's approach to managing HIV disease. This is a safety study of medicines used in the Siddha tradition of South India. This tradition is a complete medical system with means of diagnosis, patient evaluation and treatments that include botanicals, minerals, exercise, and diet, not unlike the way that Ayurvedic, Tibetan or Chinese medicinal systems have developed. Siddha began in the southeastern state of Tamil Nadu. Here, the team worked with the Gandeepam group to assess a treatment that they have used to manage HIV disease in a very rural area. CD4 counts, viral load and other blood chemistry will be monitored. The Mt. Sinai team will act as technical experts in the development of clinical trial design. Included in this grant will also be an evaluation of creating a "FAIR TRADE" agreement, should in fact the intervention under study prove efficacious.
Milk Thistle study. A study of the safety and tolerability of milk thistle (Silybum marianum) in a double-blind, randomized and placebo-controlled study among HIV/HCV coinfected individuals. We will be looking to see if there is any problem with antiretroviral blood drug levels as well as obtaining preliminary evidence on biochemical markers. The study will last about a year.
The "TI" Prolongation Project. One means of managing ARV side effects is to stop taking the drugs for a period of time. Many do this for their own reasons, however, studies are providing guides as to what conditions (i.e., relative to T cell counts, viral load, length of interruption) may be most ideal. These breaks in drug therapy are known as Treatment Interruptions (TI). A pilot study of a Chinese medicine protocol, being undertaken in New York City, was created by two member's of FIAR's team, Mark Kuebel, L.Ac. and Fred Blair, L.Ac. Both are Chinese medicine practitioners. The hope is that the herbal formula they developed will be a novel means of extending a structured treatment interruptions. Rather than simply stop medications and await the inevitable decline in CD4 count and rise in viral load, might it be possible to reduce viral activity to a low level with a treatment that detoxifies the body and prevents major AIDS symptoms from developing during the interruption? Using their formula of Chinese herbs, a pilot study is being conducted with volunteers to evaluate its anti-HIV effects.
Cholesterol Study. To ascertain if dietary supplement(s) may improve blood lipid profile associated with antiretroviral therapy by reducing elevated LDL cholesterol. Secondary endpoints include the potential for such an intervention to induce a reduction in triglyceride level as well as an increase in HDL cholesterol. FIAR has developed a preliminary concept sheet for this study (available upon request). The proposed study design is a factorial or tree design, the base of which is niacin versus inositol hexanicotinate (another form of niacin). A third placebo arm is under consideration. Patients in each arm would then be further randomized to receive carnitine or placebo. Then a third randomization would further divide patients to receive hawthorn berry extract (or possibly guggul lipids). This design would allow a better understanding of whether individual agents or some combination would be most effective in managing antiretroviral related blood lipid disturbances.
Combination herbal therapy. A number of botanical interventions have been identified that may have some direct impact on slowing HIV disease by lowering viral load. Some have been studied individually with results ranging from equivocal to modest. But as AZT monotherapy is not advisable due to the rapid development of resistance, it may well be that combinations may be effective. One case series of reports that Mr. Carter worked on for DAAIR included curcumin (Curcuma longa, L.), glycyrrhizin (an extract of licorice), SPV-30 (an extract of boxwood, Buxus sempervirens, L.) and bitter melon (Momordica charantia, L.) A number of other botanicals have been identified for which there is a reasonable basis to conduct small, focused clinical studies. This may be of particular relevance to resource poor areas, where antiretroviral therapy is not yet widely available. It may also be important for people who wish to delay disease progression as long as possible to delay the need for antivirals, as well as to extent the length of a structured treatment interruption.
Monolaurin Study or lauric acid capsules (900 mg or 3 capsules/day) for the following:
HCV/HIV Coinfection Studies. FIAR is also interested in developing protocols for hepatitis C (HCV) and HIV coinfection. As noted above, FIAR and Mount Sinai are studying milk thistle in HIV/HCV co-infection. Additional studies are planned using the panel of surrogate markers of liver fibrosis and/or hepatitis viral load. Interventions of interest include NAC, alpha lipoic acid and various combinations of botanical medicines rooted in Chinese, Ayurvedic and African traditions.
Other studies were raised in a July meeting of the AIDS Treatment Activist Coalition and may be reviewed in the associated report on the CAM Affinity Group. A study proposal for Moducare Sterinols has also been suggested.
FIAR is considering studies to be conducted in some resource poor nations. Due to the extreme need in these areas, FIAR plans to prioritize development of these studies over domestic studies. In countries like India, Thailand, Nepal and in African nations, ARV treatment is unavailable for the majority.
However, there are reasons to believe that some botanical medicines may be able to slow progression, delaying the need for ARV. The best effect of such interventions is probably earlier in disease and in delaying progression. Thus, it is critical to create an environment where treatment and prevention are linked. This may give people confidence to be tested earlier. Even small increments in the reduction of the overall progression rate could have enormous benefits both individually and for local economies by delaying the need for costlier ARV interventions and OI management, prophylaxis and treatment.
In addition, HIV testing and other diagnostics are not always widely available. As has recently become more widely accepted and understood, testing is stymied when treatment is unavailable.
FIAR wishes to develop models that combine treatment, access to traditional medicine care, evaluation of such approaches in a clinical trial setting along with providing access to ARV therapy and treatment for opportunistic infections for those in need of it. This may serve as a model for comprehensive care, while recognizing the need to minimize costs. Validated technologies such as spot-blood testing for diagnosing HIV disease (obviating the need for tubes of blood and the need for refrigeration), alternative p24 testing for viral load, Dynabeads for CD4+ counts, etc., will be considered as needed.
More detailed budgets for such programs will be developed as the concept sheets are developed. However, a guide is provided through the model of testing of antibiotic therapies for tuberculosis. As reflected in The Economics of TB Drug Development from the Global Alliance for TB Drug Development (October, 2001), the per patient cost of early phase II studies is approximately $1,881 in Uganda (including fixed and variable costs). FIAR envisions conducting studies at single sites of approximately 30-50 patients. However, these figures will be more accurately assessed when the study interventions are specified, the best methodology identified and other ancillary costs for study implementation are established. However, this gives us a figure of approximately $94,000 for a 50-patient study. Through the use of various validated, lower-cost diagnostics and other interventions, we may be able to pare those costs down.
Legal agreements will be drawn up prior to study commencement to address issues related to the commercialization or patenting, should such a need arise, of any interventions shown to be of benefit. Such benefit, of course, may be transferred to other countries and cultures, including people living with HIV in the United States. See the discussion on "Fair Trade."
One goal of these projects is also to locally introduce antiviral therapy, probably using generic medications available in India, to local communities. Currently, there is no access to antiviral therapy in Nepal, for example. We hope to structure a study with thresholds of CD4 count or viral load to establish crossover arms into ARV therapy should the traditional intervention not be adequate to control disease activity.
The South India Project:
The Nepal Project: Treatment Added to Prevention:
Thus, having such interventions available will make it easier to link testing with treatment. People will gain confidence that a positive test result may be accompanied, as needed, with access to treatment.
A Dharmsala Project: Testing, Counselling and Treatment:
Thai Holistic Hospital and Rosana Tositrakul:
Traditional Healers in Africa:
Please write to FIAR with your comments about these ideas as well as suggestions for clinical studies that you would like to see conducted! (Note: there isn't a return page after you click submit, but if you watch the bottom of your browser, you'll see that the message was sent.)