Micronutrient deficiency and treatment adherence in a randomized controlled trial of micronutrient supplementation in ART-naïve persons with HIV.

INTRODUCTION: The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection. OBJECTIVE: We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions. METHODS: Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS). RESULTS: Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants. CONCLUSION: Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00798772.

Elevated levels of vitamin B12 and folate in vertically infected children with HIV-1.

OBJECTIVE: Neurologic and hematologic abnormalities are common in HIV-infected children and may be related to concomitant deficiencies in serum B12 and folate, which are highly prevalent in HIV-infected adults. We sought to determine the prevalence of B12 and folate deficiencies in HIV-infected children in the United States. METHODS: Cross-sectional information on demographics, folate and B12 levels, hematological parameters, concurrent CD4%, HIV-viral load and antiretroviral regimens were abstracted from the medical records of 103 vertically infected children followed in an outpatient pediatric HIV clinic in the Bronx, during 2001-2002. RESULTS: Mean age was 10 years (+/-4.4 years), 46% were male, 53% African-American and 46% Hispanic. Nineteen percent had significant immunologic suppression and 18 children had AIDS. All were receiving combination antiretroviral therapy and 66% were on a protease inhibitor-based regimen. Sixteen were taking cotrimoxazole prophylaxis. None were taking multivitamins or manifested clinical evidence of gastrointestinal malabsorption. All patients had serum folate or B12 levels within or above the normal range. Children with elevated B12 were significantly more likely to be younger (P = 0.0002) and have higher mean folate levels (P = 0.0004) compared with children with normal serum B12. In a multivariate logistic regression analysis, factors independently associated with elevated levels of vitamin B12 included: elevated serum folate [odds ratio (OR): 3.2; P = 0.01], nonnucleoside reverse transcriptase inhibitor use (OR: 0.38; P = 0.05) and female sex (OR: 0.67; P = 0.42) CONCLUSION: Folate and B12 deficiencies are uncommon in HIV-infected children in the United States, suggesting that routine supplementation with B12 and folate is not indicated without confirmation of micronutrient deficiency.

An investigation of the relationship between vitamin B12 deficiency and HIV infection.

The symptoms of vitamin B12 deficiency and several symptoms common to HIV infection overlap. Additionally, persons with HIV infection have frequently been found to have vitamin B12 deficiency. Therefore, the issue of concern is the prevalence of B12 deficiency in HIV-infected persons. A retrospective study of 63 medical records in a midwestern urban veterans affairs medical center provided the data for this study. Data were collected and analyzed for relationships among B12 levels, certain hematologic components, medications, symptomatology, and immune status. A chi-square goodness-of-fit test demonstrated a significant prevalence of B12 deficiency among persons with HIV disease, and chi-square two-way tables demonstrated significant relationships between B12 deficiency and weight loss and diarrhea. Prevalence of B12 deficiency in persons with HIV infection has been shown to be significant, indicating that B12 deficiency screening in persons with HIV infection may need be done to aid the health care provider in planning the best possible care. Further research is needed to corroborate these findings.

Selected vitamins in HIV infection: a review.

In this article we review published studies on the role of serum micronutrient levels in the natural history of HIV infection. Specifically, we have focused on vitamins B12, E, A, and beta-carotene. Deficiencies of one or several of these vitamins have been associated with an accelerated progression of HIV infection to AIDS. Most investigators have used serum micronutrient levels as an indicator of vitamin nutriture. However, serum levels are not always the most sensitive or specific indicators of vitamin status. Nonetheless, serum vitamin levels are relatively easy to obtain and have been studied in various HIV-infected populations in individuals at different stages of disease. Low serum B12 levels have been associated with increased neurologic abnormalities, more rapid HIV disease progression, and increased AZT-related bone marrow toxicity. Low serum vitamin E levels have been associated with an increase in oxidative stress in HIV-infected individuals. However, early studies of vitamin E supplementation suggest that vitamin E may have important immunostimulatory properties. Studies of vitamin A deficiency in HIV-infected populations have shown that low serum vitamin A levels are associated with increased mortality, more rapid disease progression, and increased maternal-fetal transmission. However, there is little evidence that vitamin A supplementation, beyond the correction of deficiency, is beneficial in HIV infection. Finally, several clinical trials of beta-carotene supplementation have failed to show significant or sustained improvements in the immune response of patients with HIV infection or AIDS.