Exactly one decade ago, at the 4th International Conference on AIDS in Stockholm, numerous reports were presented on the widespread use of AL-721 (an egg yolk derivative manufactured largely in Israel) and dextran sulfate (a heparin relative obtained frequently from Japan). Although safe and well-tolerated, both were panned as ineffective.
The term "possible cure" -- seven years before the potential of "eradication" shone over the 1996 11th World AIDS Conference in Vancouver -- was used to describe initial reports of success with compound Q, tricosanthin root, as they surfaced in 1989. (Although numerous studies were presented subsequently which touted its possible efficacy, the toxicity -- including the reports of neurological deaths in several people with low CD4 counts -- led to its fading from the HIV arsenal.)
Successful "holistic" treatments for HIV/AIDS have yet to emerge from the myriad of those studied and tried. Although probably hundreds of substances have been used, the reason for the lack of a standard may fall into any of several categories (see chart on this page).
Considering that an official session on alternative and complementary therapies was not presented at the 12th World AIDS Conference in Geneva (conference organizers made do with a late-hour Community Symposium on Day 3), it would appear that Western medicines gobbled up the conference-goers, if not the other way around!
We did, however, have an opportunity in Geneva to review more than 30 posters addressing alternative approaches. Many of these posters, we are sad to report, lacked the proper scientific controls or data collection to compete with the "big guns." In certain parts of the world, however, such scientific diligence or access to other forms of treatments is not always feasible.
A poster presented on Monday at the conference examined plasma zinc and copper levels, and their effect on mortality, in a cohort of gay men (Abstract 12118). The Miami-based study examined measurements of these two minerals in men followed between 1987 and 1991, with a mean of 3.3 years of follow-up.
During the study period, 19 participants died of HIV-related causes. There was a statistically significant association between those who died and the presence of either zinc deficiency or a plasma copper to zinc ratio of greater than 1. (Correlations were not found for mortality with copper levels or deficiency).
This study is important in further substantiating our knowledge of correlation of mortality with measurable mineral (or vitamin) levels. Some words of caution, however, are appropriate:
That said, now would be an appropriate time for such a study to be done!
|Vitamin C||Studies not done, likely due to widespread availability of substance|
|Kombusha Mushroom||Studies not done; perhaps lack of interest|
|Bitter Melon||Studies started by halted|
|Daan Herbal Medication||Studies done but not controlled|
|Compound Q||Studies showed toxicity|
|AL-721||Studies showed lack of efficacy|
|Meditation||Difficult to quantify data|
|Oral Interferon (kemron)||Results controversial|
A 12-week placebo-controlled trial of Chinese herbal therapy published in the Journal of AIDS (1996, issue 12:4), did not show a statistically significant difference in outcomes (the authors themselves indicate that while lack of efficacy is one possible explanation, so might a study lasting only 12 weeks be insufficient to truly gauge potential efficacy). At this conference, a poster reaffirmed the increasing popularity of Chinese herbal therapies in San Francisco, where the well-known Quan Yin Healing Arts Center is located (Abstract 22483). One of that city's five acupuncture clinics which are funded by its Department of Public Health, Quan Yin reported a steady increase in the number of unduplicated clients served (see chart below):
|Year||Number Served||Percent who are persons of color|
Thus, the services are being utilized to a much greater extent (from 1990 to 1997, a 713-percent increase!), and proportionately so by people of color (and women as well). According to abstract co-author Carla Wilson, men tend to utilize acupuncture services more to address such concerns as neuropathy, sinusitis, hepatitis C, diarrhea and other GI disorders, while women tend to utilize herbal medications for treatment of gynecological and GI disorders.
It would be helpful to know more details on the Quan Yin experience:
In keeping with the conference's "Bridging the Gap" theme, a study of (+)-calanolide A, demonstrates an interesting crossover from plant-derived medications to synthetically produced therapies.
(+)-calanolide A is a naturally occurring non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been synthesized and tested in vivo during a small Phase IA single escalating dose study of 47 HIV-negative subjects (Abstract 12216). Results of the study indicate that (+)-calanolide A is well tolerated, with a minimum of adverse events. Divided into five cohorts of doses ranging from 200 to 800 mg, subjects experienced such adverse reactions as dizziness, taste perversion, headache, nausea, vomiting, diarrhea, dyspepsia, abdominal pain, pharyngitis and rash, although only the dizziness and the nausea were shown to be related to the study drug. Additionally, the drug was shown to be well absorbed, have a 15-20 hour elimination half-life, cross the blood-brain barrier, and have in vitro synergism with other antiretrovirals.
A derivative of Calophyllum lanigerum, a tree found in the swamp forests of Malaysia, (+)-calanolide A has been made into a synthetic due to the difficulty in finding more trees from which to sample. In fact, it was reported in 1993, before the reality of such a synthesis existed, that all hope was lost because the original tree could not be located. What a difference five years make!
It was the conclusion of the study that further clinical investigation is warranted. A Phase IB study has been slated for the fall to examine toxicity levels using HIV-positive participants. We could be witnessing the evolution of a "complementary" therapy into what may possibly be a full-fledged NNRTI.
Is laughter still the best medicine?
A small survey of 16 health care workers (mostly professional nurses) at a Zurich-based AIDS hospice indicated such a need to integrate humor not only amongst staff, but also between staff and patients in order to see if it provided any benefits for the patients (Abstract 22485).
In an oral presentation and subsequent poster session, nursing professionals from the Anker-Huss hospice demonstrated that systematically planned humor, rather than situational humor, may have such benefits as a decrease in pain for the patient, among other effects. The need to establish specific boundaries and to identify appropriate venues for humor is best addressed during a training period, such as the one carried out during a half-day continuing education program for this survey. Ironically, participants who completed the training ranked humor as less important compared to their prior attitudes, primarily because boundary issues involving potentially inappropriate behaviors were brought to light.
Is humor something merely funny or is there something more to it? When asked to define humor, a challenge that has often proved elusive, one participant called it "the difference between hope and resignation."
An eight-year study in India has attempted to demonstrate the benefits of an antiviral-free regimen involving 460 HIV-positive participants (Abstract 22484). This included follow-up sessions in which participants received information and counseling from 1988 to 1996 on alternative approaches such as positive attitude, yoga, vegetarian diet, vitamins, a minimum of complementary medicines (bash flower, copper, zinc, and aspirin), and a cessation of alcohol and tobacco use.
Participants (82 percent male, 18 percent female) experienced weight gain (75 percent gained between 2 and 8 kg), a CD4 count of greater than 500 cells/mm3 (in 85 percent of those studied), and a 4 percent incidence in tuberculosis. Additionally, the study reported six deaths, two of which were HIV-related, two accidental, and two due to suicide.
According to abstract co-author Geeta Bhave, ethics and inconsistent access to T-lymphocyte assays prevented a more controlled study. "I could not ethically conduct an eight-year study using a control group that would not receive any of the medicines when there is very little access to anything," Bhave told us. Despite the lack of such controls or baseline information, its merit is in providing an approach to delaying disease progression in populations which cannot access antiviral medications.
Many surveys presented asked participants if they used such complementary therapies as megadose vitamins/minerals, herbs, and metabolics in addition to their prescription medications (Abstract 42327).
One such survey was completed by 112 patients of University of California at San Francisco HIV-Gastroenterology-Nutrition Clinic. Of the 53 people who reported use of complementary therapies, a statistically significant higher CD4 count average of 353 cells/mm3 was seen versus an average of 229 cells/mm3 for the non-users.
The survey also showed significant increases in body cell mass and serum albumin levels, concluding on the basis of these markers, that users of complementary therapies were healthier than those who took prescription medications alone.
A similar pattern of usage was demonstrated in an Italian survey of 1,312 people living with HIV/AIDS. In this survey, 473 (36.1 percent) of the respondents reported using such complementary therapies as vitamins/antioxidants, homeopathy, mental techniques and herbal remedies to address symptoms or side effects from prescribed treatments, and for various quality of life issues (Abstract 42378).
A shift in the reasons for using complementary therapies was demonstrated in a survey of 96 clinic patients conducted at the Toronto Hospital between December 1997 and February 1998 (Absract 42379). The survey group, consisting of predominantly gay males over 40 years old with a mean CD4 count of 285/mm3 and a mean viral load of 35,000 copies/ml, reported a higher use of complementary therapies at that time than in the past (88 percent versus 63 percent). Previously, participants had reported the use of beta-carotene, selenium, and garlic to increase immunity and prevent the onset of symptoms; they now reported use of multivitamins, marijuana, and chiropractic care for general health and well-being. The current use or lack thereof was not related to CD4 counts, viral load, or antiretroviral use.
An interesting demographic survey of Medicaid recipients in Albany, N.Y., showed that out of 992 HIV-positive respondents, approximately 289 (30 percent) used herbal remedies, homeopathy or some form of complementary therapy (Abstract 42387). Factors that contributed to the likelihood of a respondent's use of complementary therapies included a college education, race (white and Latino more likely than African-American), a history of substance abuse (particularly crack cocaine), and a poorer perception of one's own health.
Additionally, most recipients spent low amounts of money on complementary therapies, typically at no cost, in a three-month period. Likewise, a Toronto-based survey of 2,500 HIV-positive people showed that 1,825 people (73 percent) had a usage rate of at least one complementary therapy (Abstract 42390).
An even more specific survey than the two above was conducted at the Long Island Jewish Medical Center with 212 of its HIV-positive patients -- 58 percent Latino, 34 percent African-Americans, 60 percent women (Abstract 42391). The findings revealed an 80 percent usage rate of complementary therapies with the following breakdown:
Moreover, the pattern of usage could not be associated with gender, race, or immune system function.
Not all of the surveys had positive outcomes.
An evaluation of 468 HIV-positive patients of the Infectious Diseases University of Bologna, Italy, showed that while 184 (39.3 percent) of the patients had used at least one complementary therapy during a three-month period, they had a lower adherence rate in taking their prescribed antiretrovirals and OI prophylaxis regimens than the group only on physician-prescribed medications (Abstract 42382).
Thus, a one-year follow-up showed an approximate 15 percent drop in CD4 counts, a greater than 0.3 log viral load increase, and the onset of certain clinical complications in the group using complementary therapies.
Finally, an informal survey of Cameroon-based native healers was conducted in an attempt to assess their knowledge of treating HIV and other STDs (Absract 42372). Eschewing laboratory evaluations, the healers reported using interview techniques and spiritual examinations to diagnose their patients. An AIDS diagnosis would be made on the basis of a lack of hygiene or the presence of a curse, although the healers did acknowledge treating certain HIV-related infections -- such as diarrhea, weight loss, and anemia -- by using plant extracts, invoking spirits or requesting the patients make a sacrifice to their ancestors.
Sample leaflets draped the poster presentation to show what type of outreach the healers conduct. Many of these advertisements contained claims of "curing AIDS." Thus, it was the conclusion of the authors that the healers' practices could be detrimental to other efforts to treat HIV and that they should undergo more proper training. A very good idea, indeed!
Imagine our surprise to find a six-month, randomized, placebo-controlled, double-blind study of a preparation of 35 Chinese herbs, including Ganoderma lucidum, Astragalus membranaceus and Curcuma longa (Abstract 42381).
This study was conducted in Europe and the U.S. between February and September 1996, before the widespread advent of HAART. Sixty-eight HIV-positive participants with CD4 counts less than or equal to 500 cells/mm3 and on either stable antiretroviral therapy or none at all were randomized into two groups.
By the end of the study, 53 participants remained, after two died. The other dropouts were attributed to the advent of antiretroviral therapy. Unfortunately, there were no significant differences between the study groups, in that CD4 counts declined and HIV-RNA levels remained stable in both arms.
Despite a disappointing outcome, the authors concluded that the study's merit lies in the fact that a placebo-controlled trial could be done using Chinese herbs. As cited in the Journal of AIDS (1996, issue 12:4), an earlier placebo-controlled study of Chinese herbal therapy also yielded no statistically significant outcome in the treated group.
Another controlled study, conducted in India without the benefit of lab values, was presented on the "Kootikuppala Compound" (Abstract 42329). This mixture of ancient herbs was tested from August 1996 to October 1997 against a placebo, using 60 HIV-positive participants.
Benefits reported included weight gain as well as control of diarrhea, fever, thrush and cough, whereas the placebo group reported a "deterioration of the general condition" in 80 percent of that study arm. The only reported side effect was stomach bloating in 5 percent of the participants. Due to a lack of access, CD4 counts could not be recorded. Again, the lack of precise data and certain vagaries regarding the symptoms of the placebo group keep this study below the threshold of true science, but the low price and availability of the herbs warrant further and expanded studies, according to the authors.
Refuting past claims made by practitioners of Siddha that these herbal medicines can either "cure" or "control" HIV, another comparison study (Abstract 42395) divided 10 participants into two groups. The first group received AZT, 3TC and indinavir or nelfinavir; the others received Siddha medicines, consisting of Leyham and Rasayanas herbs.
Using HIV-RNA assays, CD4 and CD8 counts at baseline, three months and six months, the group receiving HAART exhibited significant clinical benefits while those receiving Siddha exhibited no changes other than weight gain and increase in appetite. While ceding that the HAART arm produced more significant results, the authors concluded that further studies were warranted.
A controlled study from Honolulu sought to demonstrate the benefits of self-management and coping skills on the immune system and quality of life of 40 HIV-positive participants (Abstract 42374). Twenty in the random group explored such techniques as breathing imagery, progressive relaxation, cognitive restructuring, problem-solving and education classes, while the control group received their usual treatment regimens.
The study techniques explored appeared to have no direct effect on CD4 values, but the group experienced an improved well-being and enhanced coping skills. This appears to be another study that fails to link the use of alternative skills-building techniques to improved lab diagnostics, but does offer insight into improving quality of life.
Can massage therapy alleviate the pain associated with peripheral neuropathy?
A small study, consisting of seven HIV-positive participants with painful neuropathy in the feet and prior experience with other types of pain relief medications, examined the question by providing eight massage sessions between September 1995 and October 1996 (Abstract 42376). Investigators used the Brief Pain Inventory (BPI) to quantify levels of pain prior to occupational therapy massage and upon completion of the eight sessions.
Five participants reported a reduction in pain by half (3.2 on a scale of 1 to 7), while one reported a worsening of pain, and the other reported no change. It is important to note that the two non-responders were both diabetics. Thus, the authors of this tiny study concluded that massage therapy may have some palliative effect on non-diabetic, HIV-positive individuals.
An open label study of PV150896, an herbal formulation, was conducted in Mumbai, India on 21 HIV-positive participants (Abstract 42385). Surrogate markers included CD4 counts, weight, CBC, liver and renal activity.
Although the poster presentation did not contain this information, this one-year study claimed that participants saw elevated CD4 counts, did not experience weight loss, remained asymptomatic, and had normal liver and renal panels. This is another inexpensive, accessible herbal medication that may merit further study.
What can be said about this collection of studies?
If any of them were keeping HIV-infected persons from receiving more widely tested and validated regimens, we (among many others) would not approve. Nevertheless, pharmaceutical companies and ACTG lookalikes are not exactly "invading" developing nations with study designs and randomization protocols.
A word of historical perspective: Not long after the discovery of HTLV-III as the causative agent of AIDS in the early '80s, pharmaceutical companies began a frenzied scramble to find chemotherapeutic agents. One of these -- literally taken from the shelves where it had been laying for more than a decade after "failing" as a cancer chemotherapeutic agent -- was given the name Compound S. In vitro, it suppressed HIV replication. Once tried, it seemed to be effective in vivo as well.
This agent -- which might have seemed "alternative" in 1985 -- is known today as AZT.
Show me the rupees!
An abstract claiming Siddha medicines can "cure" HIV-positive persons was listed in the Conference Record (Abstract 22213).
This study from Kallupitti, India, claims to have administered Siddha medicines to 500 people living with HIV over the last three years, curing five people. The abstract concluded with a call for further research, and more importantly, financial support. Imagine our anticipation as we paced back and forth in the poster area, waiting breathlessly for the abstract's author to appear and display his information. Were we about to stumble upon the cure at last? We bided our time by formulating question after question to pose.
What are Siddha medicines? How did you determine that a cure was attained? Were the study participants using any other therapies? What type of follow-up has been performed? What is your study endpoint? And on and on. We checked the clock. We had been waiting several hours and another session would start soon. Alas, the poster slot remained empty.
Eventually, we grew tired and walked away with a humorous little laugh -- not the kind of humor that lies somewhere between hope and resignation, but instead, somewhere between bewilderment and exasperation.