Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial.

OBJECTIVE: To examine the immunologic, metabolic, and clinical effects of broad spectrum micronutrient supplementation in HIV-infected patients taking highly active antiretroviral therapy (HAART). DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial. METHODS: Forty HIV-infected patients taking a stavudine and/or didanosine-based HAART regimen were prospectively randomized to receive micronutrients or placebo twice daily for 12 weeks. Data were collected at 4-week intervals including immunologic, metabolic, and clinical measurements. The study examined the effect of micronutrient supplementation on immunologic parameters as the primary end point. The secondary end points were metabolic and clinical effects and distal symmetrical polyneuropathy. RESULTS: The mean absolute CD4 count increased by an average of 65 cells in the micronutrient group versus a 6-cell decline in the placebo group at 12 weeks (P = 0.029). The absolute CD4 count increased by an average of 24% in the micronutrient group versus a 0% change in the placebo group (P = 0.01). The mean HIV-1 RNA decreased in the micronutrient supplementation group, although not significantly. Neuropathy scores improved in the micronutrient group by 42% compared with a 33% improvement in the placebo arm. This difference did not reach statistical significance. Fasting serum glucose, insulin, and lipids were not adversely affected in the patients taking the micronutrients. CONCLUSIONS: Micronutrient supplementation can significantly improve CD4 cell count reconstitution in HIV-infected patients taking HAART. The micronutrient supplement tested was well tolerated and may hold promise as an adjuvant therapy in the treatment of HIV. Further investigation is warranted.

Update on D-ala-peptide T-amide (DAPTA): a viral entry inhibitor that blocks CCR5 chemokine receptors.

Peptide T, named for its high threonine content (ASTTTNYT), was derived by a database search which assumed that a relevant receptor binding epitope within env (gp120) would have sequence homology to a known signaling peptide. Binding of radiolabeled gp120 to brain membranes was displaced by peptide T and three octapeptide analogs (including "DAPTA", Dala1-peptide T-amide, the protease-resistant analog now in Phase II clinical trials) with the same potency that these four octapeptides blocked infectivity of an early passage patient isolate. This 1986 report was controversial due to a number of laboratories' failure to find peptide T antiviral effects; we now know that peptide T is a potent HIV entry inhibitor selectively targeting CCR5 receptors with minimal effects on the X4 tropic lab adapted virus exclusively in use at that time. Early clinical trials, which demonstrated lack of toxicity and focused on neurological and neurocognitive benefits, are reviewed and data from a small ongoing Phase II trial--the first to assess peptide T's antiviral effects--are presented. Studies using infectivity, receptor binding, chemotaxis, and blockade of gp120-induced neurotoxicity in vitro and in vivo are reviewed, discussed and presented here. Peptide T and analogs of its core pentapeptide, present near the V2 stem of numerous gp120 isolates, are potent ligands for CCR5. Clinical data showing peptide T's immunomodulation of plasma cytokine levels and increases in the percentage of IFNgamma secreting CD8+ T cells in patients with HIV disease are presented and suggests additional therapeutic mechanisms via regulation of specific immunity.