LDN and HIV/AIDS
[Editor’s Note: This page is in the process of being upgraded to our new format.]
See also these in-depth historical reports on LDN for HIV/AIDS:
Since the mid-1980's, low dose naltrexone (LDN) has consistently demonstrated a markedly beneficial effect in the treatment of HIV/AIDS. There are a score of such patients who, even today, continue to successfully use only LDN. When combined with HAART, LDN has shown itself to be an absolute preventive for lipodystrophy, as well as a synergistic therapy that diminishes viral breakthroughs and bolsters the restoration of CD4 cell levels.
> Treating HIV Using LDN Alone
Dr. Bihari reports that, as of November 2001, a group of 18 such patients had an average of 9.5 years of known HIV-positive status. They had been taking LDN continuously for an average of almost 7 years, and none had participated in regular maintenance therapy with HAART. Had these patients been untreated, their CD4 counts by now should have been at quite low levels and their clinical status should have been perilous.
Instead, the most recent laboratory data for these patients shows that the vital indicators of immune status have, on average, declined only minimally during the many years. The average CD4 count within the group is 445 cells (normal = 550-1500) and the average CD4% is 28.6% (normal = 27%-53%). And, indeed, they all remain free of opportunistic infections and other indicators of AIDS.
All of these patients started with CD4 counts of greater than 300. Dr. Bihari indicates that most patients with lower CD4 counts showed a decline in CD4 number and percentage over time, though much more slowly than untreated patients used to.
> LDN Plus Antiretroviral Therapy
Since the advent of HAART 5 years ago, Dr. Bihari has used it in combination with low dose naltrexone in all of his patients with lower CD4s. As of 2002, nearly all of his 175 patients in this category are on at least one protease inhibitor and either nevirapine or two nucleoside analogues. The group who began 5 years ago numbered 102 patients; there have been 3 dropouts since. There have been at least three interesting findings in this group:
> HIV/AIDS in the Developing World
A new project has been initiated with the cooperation of Dr. Bihari. This aims to acquaint all of the developing nations about the potential of LDN in dealing with the AIDS pandemic.
Examples of patients with successful treatment outcomes,
(Note: patients listed started naltrexone at the 3mg dosage. Beginning November 2000, all patients switched to naltrexone 4.5mg at Dr. Bihari's suggestion.)
V., a 47-year-old man, was diagnosed HIV-positive October 1989, but did not begin taking LDN until June 1992. In April 1992 he showed a CD4 count of 580 (CD4%=29). In July 1999, after 7 years on LDN with no antiretrovirals, his CD4 count was up, at 776 (CD4%=29.4). His general health status as of an April 2000 office visit to Dr. Bihari was good.
M., a 53-year-old man, was diagnosed HIV-positive in July 1990. He started on LDN January 1991, with a baseline CD4 count of 742. More than 10 years later, his CD4 count was slightly higher, at 778. At his latest office visit to Dr. Bihari, in September 2001, he was found to have mild neuropathy and lymphocytosis. At no time has this patient taken antiretroviral medication.
L., a 37-year-old woman, was diagnosed HIV-positive in March 1992, and began taking LDN 5 months later. Prior to starting on LDN, she took AZT for an unspecified period of time. Her CD4 level, as measured in April 1992, was 321 (CD4%=50.3). Her latest test results, as of June 1999, showed a CD4 level increase to 444 (CD4% had decreased to 42.9). She had never taken antiretrovirals. In her latest office visit to Dr. Bihari (January 2001), she was pregnant and doing well. She recently gave birth to an HIV-negative baby.
S., a 40-year-old man, was diagnosed HIV-positive in 1992, and began taking LDN in December 1993, at which time his baseline CD4 count was 422 (CD4%=20). His latest lab tests, administered December 2001, after 8 years on LDN with no antiretrovirals, showed a CD4 count of 756 (CD4%=25). His general health status as of his latest visit to Dr. Bihari (December 2001) was excellent.
G., a 48-year-old man, was diagnosed HIV-positive and began taking LDN in May 1997. Measured in March of 1997, his baseline CD4 count was 557 (CD4%=33). His most recent lab test, October 2001, showed a CD4 level increase to 718 (CD4%=42). Health status was good as of a November 2001 office visit. Note: This patient began taking the antiretrovirals Crixivan and Viramune at the same time he started on LDN, but stopped taking them at Dr. Bihari's suggestion after three and a half months.
Example of patient on antiretroviral therapy having prompt response to lipodystrophy when LDN added (June 2002):
M., a 53-year-old woman, not only had diabetes, which required a moderately high dosage of insulin (90 units daily), but also was suffering from lipodystrophy as a complication of her AIDS therapy. In early May, Dr. Bihari noted that he expected LDN would combat her lipodystrophy (which includes insulin resistance) and therefore would probably decrease her insulin needs. Three weeks later, he saw her again for the first time since LDN had been started. Her insulin requirements had dropped from 90 units/day to 20 units/day during those three weeks, and her "buffalo hump" (a swelling at the upper back/lower neck area characteristic of lipodystrophy) had regressed by two-thirds. Her swollen abdomen had begun to recede, enabling her, she said, to cross her legs "for the first time in a year".
What Patients Say
LDN Conference presentation (2006). William Way spoke on the LDN Advocates Panel at the April 2006 LDN Conference on the NIH campus in Bethesda, Maryland. He described having first tested positive for HIV 16 years ago—since that time he has used nothing stronger than nightly LDN to treat the HIV infection. During these many years he reports that his CD4 cell count has, for the most part, remained in a favorable zone, and he has been symptom free. In contrast to virtually any other person who has carried an HIV infection for many years, Mr. Way has never had to use antiretroviral drugs, thus avoiding the attendant expense, annoying schedules, and risk of side-effects. Mr. Way's entire talk can be viewed here.
Recent reports (2005). Detailed reports from an HIV-infected patient, who has been taking only LDN for his disease for the past 12 months, present strong evidence for the efficacy of LDN in treating HIV. His comments are reprinted in the HIV/AIDS subsection of the linked page "What Others Are Saying About LDN" (his are the three messages dated 2005). We hope that all the developing nations that are struggling to treat their HIV-infected citizens will take note.
Phone survey (2001). In November 2001, seven of Dr. Bihari's HIV-positive patients who take LDN without antiretrovirals were interviewed by telephone. Here are some of their responses to the following questions:
How would you describe your experience with using LDN?
"Absolutely positive. There were really no other choices [when I was first diagnosed]. LDN gave me some hope. Over time, my [CD4] counts never dropped. I kept waiting, and they just never dropped. So far, it's been really great. I believe in LDN—it makes sense to me."
"No negative aspects whatsoever. LDN has, I believe, kept my CD4 count from dropping—it has been the same since I started to take LDN (in 1991) 300 to 350, in that range. I remember when I first started to take it, I felt very different—after a month I felt better all of a sudden. About that time my roommate said to me one day: 'You look so different; you look so much better; your face looks so healthy.' It's been very positive—and it's inexpensive. I believe it's been the major factor in keeping me healthy."
"No negative aspects at all. My viral load has been stable ever since I've been diagnosed and taken this medication. It's been great—no side effects or anything negative about it; everything's been positive."
"I'm basically doing pretty well without being on any of the protease inhibitors ever."
"Sleep was difficult [on LDN] for 2 weeks or a month—I felt buzzy. I learned to take it closer to bedtime, which helped. Only for a short period was this a problem. Benefits: my viral load has regularly been undetectable or negligible. LDN has been very good for me, non-problematic, inexpensive. It seems like it's had a very good effect on my life."
"No negative aspects. My [CD4] numbers have maintained—up around 800 or 900 since day one."
"No negative aspects at all. LDN is what's helped me a lot over the years. I've been HIV positive for almost 15 years now, and have never been sick with any symptoms related to HIV. I think that's mostly because of LDN."
LDN has been in use in the treatment of HIV/AIDS since the completion of a double-blinded placebo-controlled trial in 1986. The trial showed significant immune system protection from HIV in the group given the active drug.
The development of LDN was based on several biological facts. One was the fact that naltrexone, which had been licensed in 1984 as an adjunct in treating heroin addiction, has the ability to induce increases in the endorphin levels in the body. Another was the fact that endorphins are the primary supervisors or (homeostatic) regulators of the immune system, representing 90% of immune system hormonal control. Ninety percent of the day's endorphins are produced by the pituitary and adrenal glands between 2a.m. and 4a.m.
Dr. Bihari and his colleagues then showed that endorphin blood levels averaged less than 25% of normal in people with AIDS. These facts all provided the background for the discovery of the value of LDN in HIV/AIDS. The nocturnal production of endorphins allowed Dr. Bihari and his colleagues to experiment with small doses of naltrexone taken at bedtime in order to jump-start endorphin production. They found that LDN increased endorphin production when taken at bedtime in doses of 1.5mg to 4.5mg. Doses lower than 1.5mg had no effect on endorphin production. Doses higher than 4.5mg produced no more of an endorphin boost, but did block endorphins for significantly longer, thereby reducing the benefit of increased endorphin levels.
Dr. Bihari and his colleagues carried out a placebo-controlled trial of low dose naltrexone in 1985-1986 in 38 patients with AIDS. This followed publication of considerable laboratory research in basic immunology done by Plotnikoff and others that had shown how endorphins play a central role in regulating the immune system. LDN 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 elevated endorphin levels persisted for 20 to 24 hours.
The 12-week trial showed a significant difference in the incidence of opportunistic infections. There were 5 such infections 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 patient group that took LDN and did not drop in those on placebo.1,2
After the trial, Dr. Bihari began to use LDN in his private medical practice. He was able to do so because the drug is FDA approved for another use, which is the treatment of heroin addiction at a dose of 50mg/day. In 1995, he evaluated the results associated with the use of naltrexone in 158 patients. 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, LDN 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 had been on naltrexone for as many as 7 to 8 years, with no disease progression or CD4 drop and no evidence of resistance to the beneficial effects of the drug. None of the patients experienced side effects.
Many years later, in 1998, a relevant laboratory research paper was published by Sharp et al in the journal Biochemical Pharmacology. It demonstrated that activation of delta-opioid receptors of acutely infected CD4+ T cells significantly inhibited HIV expression in those cells. [Ed. note: activation of these receptors is one of the effects of the endorphins that are stimulated by taking LDN.] 3 (abstract)
> The 1996-1998 Study
In September 1998, Dr. Bihari reported on his retrospective, private-practice based, observational study of the effects of a combination of highly active antiretroviral therapies (HAART) and LDN on HIV RNA-PCR, CD4 levels, adverse reactions and clinical status in 85 patients with HIV/AIDS.
The study was begun in August 1996 when nevirapine became widely available, 4 to 7 months after the availability of indinavir and two other new protease inhibitors. All 85 of the patients were already on LDN. Based on CD4 levels, clinical history and personal preference, 60 of the 85 were started on or were already receiving lamivudine (Epivir). Forty-nine were also on zidovudine (Retrovir) and 4 on stavudine (Zerit) with lamivudine. Twenty-five received indinavir, nevirapine and naltrexone without other antivirals. Treatment with naltrexone, zidovudine and lamivudine or stavudine always preceded the initiation of indinavir and nevirapine, by 3 to 15 months.
The age range was 22 to 74. Ten were women and 75 were men. Thirteen were African-American, 6 were Latino, and 2 were Asian-American. The mean time from initiation of indinavir and nevirapine therapy to the most recent laboratory results was 20 months. Half of the group had been on this combination for 23 months when the most recent labs were done. Patients who were on O.I. prophylaxes before starting these new antivirals were all continued on them, no matter how great the magnitude of rise in CD4 number and CD4 percentage. All patients were started on 1000 mg of indinavir every 8 hours. This was raised from the usual 800 mg every 8 hours to compensate for nevirapine-induced lowering of indinavir blood levels.
Seventy-five patients became PCR undetectable in 4 weeks and remained so. Six never reached undetectable levels. Three did reach undetectability on only one test but then quickly rose back into the detectable range. These 9 acknowledged significant and prolonged lapses in compliance with the indinavir regimen. Only one compliant patient had a sustained suppression of viral load to undetectable (for 6 months) followed by plasma viremia. Seventy-five had no detectable HIV since the first month's test.4
There was not a single major opportunistic infection in the 85 patients. One had an episode of shingles. None had thrush. All but one patient remained at their ideal weights or higher. None died or was lost to follow-up. Most patients noted a significant increase in energy, appetite and mood after adding the antiretrovirals.
Only one case of the lipodystrophy syndrome was observed in this patient group. There were, except for this one patient, no changes in fat distribution, in serum triglycerides, in blood glucose or significant rises in serum cholesterol. Since the range of incidence of this syndrome in other studies of patients on protease inhibitors varies from 11% to 35%, this appeared to be a very unusual finding. The one patient who was an exception supported the likelihood that LDN was responsible for the general protection against the lipodystrophy syndrome.
This patient was on indinavir, nevirapine and LDN for 15 months, with a rise in CD4's, undetectable viral load and no lipodystrophy. He then moved to the west coast of Canada where he was unable to obtain naltrexone, which is not yet a licensed drug in Canada. Because of his sustained viral-load suppression and positive feelings about the new antivirals, he felt the naltrexone was not crucial and discontinued it. About 8 months after stopping low dose naltrexone, he began to develop the changes in body shape associated with lipodystrophy. These physical changes were accompanied by a sharp rise in serum cholesterol, triglycerides and glucose.
Later, Dr. Bihari learned of three other patients who had stopped LDN after starting HAART, then developed lipodystrophy six to nine months later. As mentioned above, three of these four patients experienced clearing of lipodystrophy after nine to twelve months back on LDN.