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AIDS 2010: Nutritional Supplements May Slow HIV Disease Progression, Boost Immune Recovery, and Lessen Mitochondrial Toxicity

People with HIV in Botswana who used a multi-vitamin supplement experienced slower disease progression and CD4 T-cell loss, according to a study presented at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. Two smaller U.S. studies found that zinc supplements were associated with lower likelihood of immune cell decline, while antioxidants helped prevent mitochondrial damage.

Good nutrition plays an important role in health, but the benefits of specific nutritional supplements for people with HIV are not fully understood. Supplements may play a valuable role as a relatively inexpensive intervention, especially in areas where malnutrition is widespread.

Micronutrients

Marianna Baum from Florida International University in Miami and colleagues presented 3 nutrition studies at AIDS 2010. In the first study, they sought to determine whether micronutrient supplementation could improve immune function and prolong time to progression to AIDS among HIV positive people in Botswana.

Thisprospective, randomized, controlled trial included 875 adults with HIV who still had CD4 cell counts above 350 cells/mm3 and had not yet started antiretroviral therapy (ART). About three-quarters were women and the average age was about 34 years. Participants were randomly assigned to receive either multi-vitamin supplements containing vitamin B complex, C, and E, and selenium, or else placebo for 2 years.

The primary study endpoint was a drop in CD4 count to < 250 cells/mm3, the threshold for starting ART in Botswana at the time of the study. (The World Health Organization now recommends treatment initiation at 350 cells/mm3.) Questionnaires, pill counts, and plasma micronutrient levels were used to assess adherence.

Results

• Supplementation adherence was good, at 98%, and participants attended 92% of scheduled study visits.
• In an intent-to-treat analysis, participants who received supplements took significantly longer to reach a CD4 count < 250 cells/mm3 compared with those receiving placebo (P = 0.037).
• Supplement recipients also took longer to experience any event indicative of disease progression (P = 0.016).
• Supplementation appeared safe and well tolerated, with no detrimental changes in HIV viral load or metabolic profiles.

These findings led the researchers to conclude, "This study demonstrated that long-term micronutrient supplementation was safe and significantly prolonged time to CD4+ count < 250 cells/mm3."

"This evidence supports the use of micronutrient supplementation as an effective intervention in HIV+ adults in early stages of the disease in Botswana," they continued. "Nutritional supplementation prolongs the asymptomatic stage, improving patients' well-being, and may translate into financial savings and broader access to HIV treatment in developing countries."

Zinc

In the second study, the researchers looked at the effects of supplemental zinc -- which is known to play a critical role in immune function -- on immunological recovery, or CD4 cell gains on ART.

This study included 40 HIV positive participants in Miami who were on ART and had suppressed HIV viral load.  Most (90%) were men, the mean age was 46 years, and nearly 70% were African-American. Many were homeless and relied on soup kitchens for food; about half had low micronutrient levels at baseline.

Participants were randomly assigned to receive either zinc supplements (15 mg for men or 12 mg for women) or placebo for 18 months. ART regimens did not differ between the 2 groups.

Results

• 7 participants were found to have immunologic failure, defined as CD4 count < 200 cells/mm3, at baseline.
• 4 new cases of immunologic failure (CD4 count dropping to < 200 cells/mm3) were observed during follow-up, all in the placebo group.
• Rates of immunological failure were 21% in the placebo group compared with 0% in the zinc supplement group (P = 0.043).

"Zinc supplementation at nutritional levels was safe and prevented immunologic failure in HIV infected patients on stable ART," the researchers concluded. "The evidence from this preliminary study indicates a potential benefit of zinc supplementation as an adjunct therapy in HIV+ adult cohorts on ART."

Antioxidants

In the final study, Baum and colleagues looked at the association between antioxidants, immune reconstitution, and mitochondrial toxicity, which can have multiple manifestations including lactic acidosis, lipoatrophy (fat loss in the face and limbs), and peripheral neuropathy.

HIV infection itself and the long-term use of certain antiretroviral drugs -- especially the "d-drug" NRTIs stavudine (d4T, Zerit) and didanosine (ddI, Videx) -- are associated with increased mitochondrial damage and oxidative stress, the researchers noted as background.

This analysis included 25 HIV positive adults on stable ART with viral load < 50 copies/mL. The population was similar to the study described above; just over half were men, the average age was 49 years, and the mean CD4 count was about 500 cells/mm3.

Participants were randomly assigned to receive micronutrient and antioxidant supplements containing vitamin B complex, C, and E, selenium, zinc, N-acetyl cysteine, and alpha-lipoic acid, or else placebo, for 8 weeks.

Results

• Antioxidant supplementation was associated with trends toward increased CD4 percentage (P = 0.06) and CD4/CD8 ratio (P = 0.09), though they did not reach statistical significance.
• Participants receiving supplements showed a significant increase in oxidative phosphorylationcomplex IV, a biomarker for mitochondrial toxicity (P = 0.016), which remained significant after controlling for baseline levels (P = 0.046).
• Supplement recipients also had significantly less insulin resistance after controlling for body mass index, determined using the HOMA-IR method (P = 0.09).
• Antioxidant supplementation was safe and well-tolerated.

"Longitudinal studies with adequate sample size are needed to evaluate whether antioxidants given as adjuvant therapy with ART improve immune reconstitution and reduce mitochondrial toxicity and oxidative stress in HIV+ patients on ART," the investigators concluded.

Taken together, these findings indicate that nutrient supplementation may have beneficial effects on immune function, especially for people starting with low levels.

"We recommend that, at least in Africa, people in the early stages of HIV infection have their nutritional status monitored and receive supplements when appropriate," Baum told Medscape. "This should probably occur in the United States too."

Investigator affiliations: Florida International University, R Stempel College of Public Health and Social Work, Miami, FL; Johns Hopkins University, Bloomberg School of Health, Baltimore, MD; Harvard University, Harvard School of Public Health, Boston, MA; Botswana Harvard AIDS Institute, Gaborone, Botswana; PATH, Washington DC; University of Miami, Miller School of Medicine, Miami, FL.

8/13/10

References

M Baum, A Campa, S Lai, and others (Dikotlana study team). Micronutrient supplementation to prevent disease progression in HIV-infected adults in Botswana. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract MOPE0100.

M Baum, R Marlink, D Jayaweera, and others. Effect of antioxidant supplementation on immune reconstitution and mitochondrial damage. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract MOPE0102.

A Campa, D Jayaweera, S Lai, and others. The effect of zinc supplementation on immune failure in HIV infected adults on stable antiretroviral therapy (ART). XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract MOPE0101.

Other Source

N MacReady. Supplements Improve Outcomes for HIV-Positive Patients. Medscape. July 20, 2010.