Curcumin: Clinical Trial Finds No Antiviral Effect

A clinical trial with 40 volunteers, reported at the 3rd Conference on Retroviruses and Opportunistic Infections, found that curcumin, a popular "alternative" treatment for HIV, had no effect in reducing viral load or in increasing CD4 counts.(1) This trial was conducted by the CRI (Community Research Initiative) of New England, a community-based research organization.

Curcumin is an ingredient of turmeric, a spice used in making curry; it is the substance which gives curry its yellow color. Laboratory tests had shown that curcumin has substantial anti-HIV activity in cell cultures, at concentrations not damaging to the cells.(2) A 1994 clinical trial of curcumin by AIDS Research Alliance (named SEARCH Alliance at that time) was inconclusive, largely because of great unexplained variability in the viral load results. [For historical background on curcumin and HIV, see AIDS TREATMENT NEWS # 174 (May 7, 1993), #176 (June 4, 1993), and #198 (May 6, 1994). Our report on the AIDS Research Alliance trial is in issue #198.]

Of the 40 persons entered into the recent trial by the CRI of New England, two dropped out due to adverse events unrelated to the curcumin study. Of the other 38, 23 were randomized to a high-dose group and 15 to a low-dose group. (This study used the popular "Turmeric Power" brand of curcumin; the high dose was four capsules four times a day, and the low dose was 3 capsules three times a day.) Each group was further randomized to begin curcumin either immediately or after 8 weeks; both groups received the treatment for eight weeks. Both groups had at least two viral load tests to establish the baseline viral load value (those in the delayed-treatment group had three tests for their baseline); viral load tests were also given at 4 weeks and at 8 weeks of treatment.

The following viral load averages were published in the abstract of this study presented at the Retroviruses conference. In the high-dose group, the average viral load was 4.569 logs (37,100 copies) at baseline, 4.226 logs (16,800 copies) at four weeks, and 4.568 logs (37,000 copies) at eight weeks. In the low-dose group, the corresponding figures were: baseline 4.989 logs (97,500 copies), four weeks 4.623 logs (42,000 copies), and eight weeks (4.822 logs, 66,400 copies). On the surface, this looked to us like a statistically significant result; but we contacted the researchers and found that the apparent viral load drop, in both the high-dose and low-dose groups, was caused in each case by a single individual with a single value which was wildly out of range (in one case, more than 100 times any other viral load result from that person); the extreme values were probably due to a laboratory error. When these anomalous values were excluded, no effect on viral load was found.

CD4 cells showed a slight rise in the high-dose group (baseline average 231, four weeks 247, eight weeks 262), and a consistent fall in the low-dose group (baseline 244, four weeks 223, eight weeks 146). But neither result was statistically significant, meaning that these changes were likely due to chance and cannot be taken as evidence of any treatment effect.

Researcher Jim Hellinger, M.D., of the Community Research Initiative of New England, noted in a private communication to us that, "Despite the lack of apparent antiviral or CD4 effects, most participants liked taking curcumin, and felt better taking it, and put up with the minor GI effects. We did not plan any formal analysis of these effects, but there certainly are other ways in which curcumin might be active..." A blood test for curcumin levels, now being developed for a different study, may provide more information about why no antiviral activity was found.

Comment

In 1993 we became interested in curcumin because of its scientific rationale, and the laboratory findings of anti-HIV activity -- plus the fact that the potential treatment was safe, inexpensive, and widely available. We also heard a few early anecdotal reports of viral load reductions in patients who tried curcumin.

One of the biggest problems in AIDS treatment development is that only proprietary drugs tend to get tested -- assuring that any resulting treatment will be very expensive, and also that testing will take a long time, since proprietary substances tend to be new chemicals, not familiar drugs, herbs, or food components already in wide human use. There is a critical need for social organization to screen promising leads which for commercial reasons are not being pursued by pharmaceutical companies. Both the CRI of New England, and the AIDS Research Alliance, are to be commended for their studies of curcumin. Now that viral load testing is becoming more available, and the technology more reliable, small trials to screen for antiviral activity in people are becoming much easier and more feasible than they were in the past.

We must realize that the large majority of potential treatments which have the scientific rationale and/or laboratory or anecdotal information to justify a small trial will turn out not to be useful. But there are many promising leads among substances already available and in human use; the odds are good that at least a few of them will prove helpful. A single one that does will justify all the effort and expense of testing the others.

References

1. Hellinger JA, Cohen CJ, Dugan ME, Day JM, Cavanaugh JF, and Glidden D. Phase I/II randomized, open-label study of oral curcumin safety, and antiviral effects on HIV-RT PCR in HIV+ individuals. 3rd Conference on Retroviruses and Opportunistic Infections, January 28 - February 1, 1996, Washington DC [abstract #140].

2. Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS, and Pardee AB. Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA, March 1993; volume 90, pages 1839-1842.