Peptide T is a synthetically produced protein derived from gp120 - the protein on the surface of HIV particles which binds to the CD4 molecule on the surface of some human cells. Peptide T was discovered in 1986 when scientists were screening for gp120 derived peptides which might block HIV infection.

Test-tube studies showed that peptide T interferes with the way HIV binds onto immune cells. Specifically, it disrupts gp120 binding and HIV's use of the CCR5 co-receptor.

It was later discovered that peptide T has the same basic chemical structure as certain proteins in the brain (neuropeptides) such as VIP. A natural protein found in the brain and the gut, VIP is involved in transmitting messages (a neurotransmitter).

Peptide T is manufactured by Advanced Peptides and Biotechnology LLC.

Current use

Peptide T is an unlicensed, experimental drug. Only two controlled efficacy studies have been completed, and both have found evidence that Peptide T can improve neuro-cognitive function in people with HIV-associated dementia (Heseltine; Kosten). One study found that peptide T reduced the symptoms of peripheral neuropathy in people with HIV but another study found it had no effect (MacFadden; Simpson).

Peptide T has some anti-inflammatory effects and clinical data indicate that intravenous or intradermal injections of peptide T are an effective treatment for psoriasis in both HIV-positive and HIV-negative people (Raychaudhuri).

The only reported side-effects from peptide T have been minor, such as rash, nasal congestion and, in one study, `second puberty' (hirsutism, acne, increased libido, wet dreams, increase in testosterone). Users have also reported bouts of extreme anger which they attribute to the drug.

Taking it

Peptide T comes as a liquid which is taken intranasally (by squirting it up the nose). It can be obtained from buyers' clubs in the USA. No clinical trials are taking place in Britain.

A clinical trial of peptide T as an antiviral medication is being conducted at the St Francis Hospital, San Francisco, USA.

Key research

In vitro, peptide T has been reported to prevent HIV from infecting CD4 cells by blocking receptor sites on the CD4 molecule. Peptide T is an octal peptide which mimics and competes with both a section of VIP and a section of gp120, the HIV surface molecule which binds to the CD4 receptor. Buzy reported that peptide T and VIP can prevent gp120-induced neuronal cell death in vitro.

Simpson reported that in a phase II double-blind efficacy trial of peptide T, there were no statistically significant differences between peptide T (6mg/day for 12 weeks) and placebo in the treatment of painful peripheral neuropathy. The drug also seemed to have no effects on neuropsychological functions. The study enrolled 81participants with AIDS.

Heseltine treated 215 people with mild to severe cognitive impairment with either peptide T (2mg three times daily intranasally) or placebo for six months, followed by open-label peptide T for an additional six months. Analysis of all people who completed at least four months of treatment showed there was no difference in neuropsychological performance between the two arms. After the analyses were adjusted to take account of an imbalance in baseline CD4 count between the groups, people who received peptide T showed greater improvement (p=0.07). In particular, peptide T was beneficial for people with CD4 counts greater than 200 or with more evident cognitive impairment at baseline. Those with a baseline deficit score above 0.5 showed overall cognitive improvement while the placebo group experienced an overall deterioration in cognitive performance.

Kosten conducted a placebo-controlled, double-blind, cross-over study of 15mg or 1.5mg of peptide T daily in nine injecting drug users with early AIDS dementia. Neuro-psychological performance improved in 4/5 patients who received high dose peptide T compared to only 1/4 in the low dose group. Participants were also receiving methadone and AZT monotherapy.

Bridge reported a phase I safety and dosing study of peptide T in 14 people with AIDS. Drug was dosed from 0.1 to 3.2mg/kg/day intravenously for twelve weeks. The first six patients to complete IV treatment continued on intranasal drug (25mg/day for eight weeks). Cognitive and neuromotor function improved in patients with moderate neuro-psychological impairment compared with controls.

MacFadden reported that of nine individuals with HIV-related peripheral neuropathy treated with Peptide T (subcutaneously at an initial dose of 10mg daily, with two patients tapered to 2.5mg in order to determine the minimal effective dose), all experienced either complete or subjectively significant resolution of lower limb pain, with effects being noticed as early as two days after initiation of treatment. The pain-free interval persisted for the duration of the treatment (for 3 to 70 weeks) but pain recurred gradually within one week of stopping the drug, resolving upon reinstitution of treatment. In 2 participants, decreasing the dose to 2.5mg/day resulted in recurrence of pain, which resolved when the dose was increased to 5mg. No adverse drug effects were noted.

References

Bridge TP et al. Improvement in AIDS patients on peptide T. Lancet 2(8656): 226-227, 1989.

Bridge TP et al. Results of extended peptide T administration in AIDS and ARC patients. Psychopharmacology Bulletin 27(3): 237-245, 1991.

Buzy J et al. Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T. Brain Research 598(1-2):10-18, 1992.

Heseltine PN et al. Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment. Archives of Neurology 55(1): 41-51, 1998.

Kosten TR et al. Treatment of early AIDS dementia in intravenous drug users: high versus low dose peptide T. American Journal of Drug and Alcohol Abuse 23(4): 543-553, 1997.

MacFadden DK et al. Role of peptide T in palliation of HIV-1-related painful peripheral neuropathy. Seventh International Conference on AIDS, Florence, abstract WB 2173, 1991.

Raychaudhuri SP et al. Immunomodulatory effects of peptide T on Th 1/Th 2 cytokines.

International Journal of Immunopharmacology 21(9): 609-15, 1999.

Redwine LS et al. Peptide T blocks gp120/CCR5 chemokine receptor-mediated chemotaxis. Clinical Immunology 93 (2): 124-131, 1999.

Ruff MR et al. Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5). Antiviral Research 52(1): 63-75, 2001.

Simpson DM et al. Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. Neurology 47(5): 1254-1259, 1996.