Clinical Briefs

By Louis Kuritzky, MD

Multivitamin Supplements and HIV Disease Progression and Mortality

The greatest burden of the HIV epidemic resides outside the United States. Especially in economically lesser-privileged nations, not all individuals who might benefit from antiretroviral (ARV) treatment can obtain it. Observational studies have suggested that micronutrient supplementation (MNS) might be a favorable immunomodulator in HIV, perhaps delaying disease progression. If this were confirmed with interventional studies, a delay in onset of advanced disease would reduce the number of individuals needing ARV. Of course, MNS is also markedly less costly than ARV.

HIV-infected pregnant women (n = 1078) were enrolled beginning in 1995. Women were assigned to vitamin A (30 mg beta carotene + 5000 IU preformed vitamin A), multivitamins excluding vitamin A (20 mg B1, 20 mg B2, 25 mg B6, 100 mg niacin, 50 mg B12, 500 mg vitamin C, 30 mg vitamin E, 0.8 mg folic acid), the combination of both, or placebo.

Investigators measured CD4, CD8, and CD3 counts, and viral load; typical symptoms and signs of HIV disease such as diarrhea, wasting, thrush, and angular cheilitis were also followed.

The primary outcome (death or stage 4 HIV disease) was statistically reduced by multivitamins (relative risk = 0.71), as were many of the individual HIV-related complications (eg, thrush, cheilitis). Vitamin A alone produced no measurable benefit, and the addition of extra vitamin A to the multivitamin regimen actually appeared to reduce some of the benefits of multivitamins alone.

Fawzi WW, et al. N Engl J Med. 2004;351:23-32.

The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) Study

Clinical trials in research settings may not reflect accurately what clinicians in a non-academic milieu may anticipate, despite using the same fundamental pharmacologic tools. Drug efficacy is sometimes distinguished from drug effectiveness by defining the former as data from randomized trials, and the latter as results in the typical practitioner’s settings.

The United States Preventive Services Task Force has encouraged diet, behavioral interventions, and pharmacologic treatment as reasonable evidence-based management choices for obesity. Sibutramine (SIB) is an FDA approved tool for adjunctive pharmacotherapy of obesity, and clinical trials confirm its durable efficacy (2 years duration). Porter and colleagues studied the effectiveness of SIB in a group-model HMO.

All of the participants (total n = 588) participated in an educational program for weight management, including seminars and visits with prevention specialists. Half of the group also received SIB, beginning with 10 mg daily, increased to 15 mg daily if the patient had not lost at least 4 pounds at the and of the first month of treatment. Sibutramine dose was decreased to 5 mg if adverse effects on pulse or BP occurred.

At 6 months, weight loss in the SIB group was substantially greater than the comparator group (6.87 kg vs 3.1 kg); this disparate success was evidenced at 1 year, with maintenance of weight loss still superior in recipients of SIB. These results closely reflect data generated by academic clinical trials. The efficacy and effectiveness of SIB appear comparable.

Porter JA, et al. Am J Manag Care. 2004;10:369-376.

Trial of Atorvastatin in Rheumatoid Arthritis (TARA)

Modulation of lipid levels appears to be the primary mechanism for beneficial effects of statins upon cardiovascular disease. At the same time, statins have been demonstrated in-vitro to impact on numerous aspects of inflammatory pathways, such as adhesion molecule expression and leukocyte cytokine release; similarly, vascular effects including smooth muscle apoptosis and endothelial cell function have been shown.

It has been suggested that the exaggerated cardiovascular risk associated with rheumatoid arthritis (RA) might be mediated to some degree by inflammatory pathways common to both rheumatoid arthritis and the vasculopathy. Based upon promising animal data, a study in human RA (n = 116) was undertaken to specifically examine the effects of atorvastatin (vs placebo) upon 1) a rheumatoid disease activity score (primary outcome), and 2) various secondary outcomes, including laboratory data (CRP and ESR), swollen joint count, and others. Atorvastatin was administered in a dose of 40 mg daily, in addition to traditional RA disease-modifying therapy.

After 6-months treatment there was a statistically significant improvement in the RA disease actvity score, CRP, ESR and swollen joint count. There was no adverse event signal amongst atorvastatin subjects greater than placebo. Statins may have a role in attenuating cardiovascular risks in RA through both modulation of inflammatory processes and dyslipidemia.

McCarey DW, et al. Lancet. 2004;363:2015-2021.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.