www.lowdosenaltrexone.org www.ldninfo.org

LOW DOSE NALTREXONE IN THE TREATMENT
OF HIV INFECTION

Bernard Bihari, M.D.
September 1996

This is a brief summary of the history of the development of low dose naltrexone as an immune-enhancing agent in the treatment of HIV/AIDS. My colleagues and I carried out a placebo- controlled trial of low dose naltrexone in 1985-1986 in 38 patients with AIDS. This trial was based on a large body of research in basic immunology that demonstrated that endorphins are the key hormones involved in the body's regulation of the immune system. They also regulate communication between the brain and the immune system. A survey of serum beta endorphin levels in 10 AIDS patients showed that they were less than one-third of normal. Naltrexone was chosen for its ability to induce increased production in the body of two endorphins, beta endorphin and metenkephalin. A dose was chosen (3.0 mg. at bedtime) that raised endorphin levels without blocking them for more than a few hours. The 12-week trial showed a significant difference in the incidence of opportunistic infections. There were 5 in 16 patients on placebo and none in 22 patients on the drug. Lymphocyte mitogen responses declined on placebo and not on the drug. Finally, the pathologically elevated levels of acid-labile alpha interferon, present in all 38 patients, declined significantly in the patients on the drug and did not in those on placebo.

After the trial I began to use low dose naltrexone in my private medical practice. I was able to do so since the drug is FDA approved for another use which is the treatment of heroin addiction, at 50mg./day.

A year ago my staff and I evaluated the results associated with the use of naltrexone in 158 patients in my practice. Only 10 were on antivirals. The results were quite striking. Patients who had taken the drug regularly as prescribed (compliant) showed no drop in CD4 cells. The average CD4 number in these patients before starting naltrexone was 358, and the average 18 months later was 368. The 55 patients who had not taken the drug, or had taken it only sporadically (non-compliant), showed a drop of CD4's from an average of 297 to 176 in 18 months. This represented a drop of approximately 80 per year, roughly the usual rate of drop in patients with HIV with no treatment. Thus, low dose naltrexone had completely stopped the CD4 drop. This stabilization of CD4's was accompanied by an arrest of disease progression. The 55 non-compliant patients experienced 25 opportunistic infections, and the 103 compliant patients only 8. Survival was also significantly different between the groups. There were 13 deaths among the 55 non-compliant patients and only one in the group of 103 compliant patients. Some patients in this study have been on naltrexone for as much as 7 to 8 years, with no disease progression CD4 drop and no evidence of resistance to the beneficial effects of the drug. None of the patients experienced side effects. See chart below.

Compliant Noncompliant
Number of patients10355
CD4# at start (average)358297
CD4# after 18 mos. (average)368176
Opportunistic Infections825
Deaths113

More recently, I analyzed the CD4 changes in 19 patients for whom I had added the combination of 3TC (Epivir) and AZT. I compared the rise in CD4's at 6 months with the rise in the New England Journal of Medicine of December 21, 1995 (vol. 333, number 25, pg. 1662) reported by an investigator working for Glaxo.

In both groups none of the patients had taken AZT previously. The major differences between the Glaxo group and my patients were the simultaneous use of low dose naltrexone in my group and not in the Glaxo group, and the average number of CD4's at the beginning of treatment. The naltrexone patients had an average CD4 count before starting these antivirals of 88 while the Glaxo group had an average of 352. The results are presented in the table below.

Baseline
CD4's
CD4's at
6 months
Number
of patients
Naltrexone group8819419
Glaxo group35239268

The Glaxo patients on Epivir and AZT experienced an average rise of 40 CD4's at 6 months. This represents an 11.3% increase. The patients on Epivir, AZT and low dose naltrexone experienced an average rise of 106 CD4's at 6 months, representing a 128% increase. All 19 of the patients in the naltrexone group had increases of at least 30%. In addition there was, in all but one, a significant increase in energy, appetite and mood. In several underweight patients there were weight gains of 10 to 50 pounds in the first 2 months.

Thus, the data from one placebo-controlled trial and two private-practice based observational studies strongly suggest that low dose naltrexone is an effective immune-enhancing agent. When used alone, it appears to significantly slow disease progression. When naltrexone is used in conjunction with the newer and more potent antiviral combinations, it accelerates immune system healing.