LETTERS
In Reply: Dr Diamond and colleagues provide analyses that examine whether CD4 cell counts and the duration of HIV infection are associated with unprotected sex in a heterogeneous sample of HIV-positive patients. As discussed in our meta-analytic review, analyses like these are informative for obtaining a better understanding of how medical factors may affect the relationship between receipt of HAART and sexual risk behavior among persons infected with HIV. Although Diamond and colleagues did not find any association between CD4 cell counts, an indicator of disease stage, and sexual risk behavior in their cross-sectional study, a recent longitudinal study1 conducted survival analyses of 190 HIV-infected injection drug users who initiated HAART during 1996-2000 and found that an increase in CD4 cell count after HAART initiation was significantly associated with engaging in unprotected sexual intercourse, a finding that is consistent with our discussion. However, given that potentially conflicting conclusions may be reached when different subsets of studies are considered, it is still important to integrate all findings meta-analytically. We encourage researchers to provide information on analyses of medical factors to assist future synthesis efforts. We agree with Drs Obermeyer and Rajkumar that there is a need for wider sampling in analyses of the association between receipt of HAART and HAART-related beliefs with sexual risk behavior, especially among populations in developing countries. Those studies would be especially useful if they assess both treatment-related variables and HAART-related beliefs, thus allowing a comparison of the 2 classes of variables and an examination of their potential interaction effects. The extent to which our meta-analytic findings can be generalized to resource-poor settings requires future evaluation after more research has been conducted in those understudied locations and populations. Meaningful comparisons across settings and populations would be fostered by adopting standard measures of these variables and beliefs across countries and collaborating in data collection efforts.2 We also wish to emphasize the importance of prevention counseling for HIV-positive persons. In many countries that are beginning to receive therapeutic resources, there is a unique opportunity to integrate prevention counseling with routine medical care at the very outset of the care process. This integration would strongly establish prevention as standard of care and help prevent patients from infecting others and potentially worsening their own health by contracting secondary infections or drug-resistant virus.3 Nicole Crepaz, PhD
[email protected] Gary Marks, PhD Division of HIV/AIDS Prevention Centers for Disease Control and Prevention Atlanta, Ga Trevor A. Hart, PhD Department of Psychology York University Toronto, Ontario 2336
JAMA, November 17, 2004—Vol 292, No. 19 (Reprinted)
1. Tun W, Gange SJ, Vlahov D, Strathdee SA, Celentano DD. Increase in sexual risk behavior associated with immunologic response to highly active antiretroviral therapy among HIV-infected injection drug users. Clin Infect Dis. 2004;38:11671174. 2. International Collaboration on HIV Optimism. HIV treatments optimism among gay men: an international perspective. J Acquir Immune Defic Syndr. 2003;32:545550. 3. Richardson JL, Milam J, McCutchan A, et al. Effect of brief safer-sex counseling by medical providers to HIV-1 seropositive patients: a multi-clinic assessment. AIDS. 2004;18:1179-1186.
Isoflavones and Postmenopausal Women To the Editor: I would like to raise some methodological concerns about the study by Dr Kreijkamp-Kaspers et al.1 First, their assumption that soy isoflavones are equipotent to conventional hormone therapy is in error. Their power analysis indicates that they should have been able to detect a 6.7% increase in bone mineral density (BMD) based on 200 participants. They should have used 2-directional hypothesis testing and calculated power based on their actual sample size and, given that this magnitude of increase is within the range previously reported for bisphosphonates,2 a 3% change in response to isoflavones over 1 year may have been more realistic. Second, the authors state that “adjustment for smoking history and baseline BMD did not change the results,” but current smoking status and antihypertensive medication use should have been taken into account statistically. Third, those participants who had more recently transitioned through menopause experienced better results in both hip and spine BMD after 1 year of soy protein intake compared with the participants in the placebo group although the interaction was not statistically significant. This difference raises the possibilities that time since menopause was critically important in dictating a treatment effect or that the power of the study was insufficient for the subgroup analysis. Fourth, I am concerned about the impact of the 12 excluded vertebral scans on the study power. Finally, compliance based on supplement use by treatment group is important to report. D. Lee Alekel, PhD
[email protected] Food Science & Human Nutrition Human Metabolic Unit Center for Designing Foods to Improve Nutrition Iowa State University Ames 1. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA. 2004;292:65-74. 2. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:11891199.
To the Editor: The study by Dr Kreijkamp-Kaspers and colleagues1 indicates that the daily intake of soy protein enriched with isoflavones has no role in improving cognitive function, BMD, and plasma lipid levels in relatively elderly postmenopausal women. Although this conclusion about ©2004 American Medical Association. All rights reserved.
LETTERS
the administration of soy isoflavones appears valid, there is good evidence that soy protein may be effective in lowering plasma lipid levels. This is supported by the metaanalysis by Anderson et al2 cited in this article. Most of the studies in this meta-analysis used far higher daily doses of soy protein than the present study did. Studies such as that of the “dietary portfolio”3 support a real benefit of vegetable vs animal protein for the reduction of hypercholesterolemia and for cardiovascular disease prevention. Cesare R. Sirtori, MD, PhD
[email protected] University of Milan University Center of Hyperlipidemias Niguarda Hospital Milan, Italy 1. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA. 2004;292:65-74. 2. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soybean protein intake on serum lipids. N Engl J Med. 1995;333:276-282. 3. Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003;290:502-510.
To the Editor: I am concerned that the study by Dr Kreijkamp-Kaspers et al1 may have failed to ensure adequate vitamin D intake and to control for serum 25-hydroxyvitamin D status among its participants. The data presented in Table 3 of the article indicate that vitamin D intake in the treatment group actually decreased from 4.27 µg (171 IU) to 3.54 µg (142 IU) during the study period. Vitamin D intake at this level would be insufficient to maintain minimum serum vitamin D levels and to sustain bone health, with a daily intake of 1000 IU suggested as the minimal dose to prevent osteoporosis.2 In addition, the city of Utrecht, from which their patient population was selected, is located in a region with a high incidence of hypovitaminosis D.2-4 Dave N. Muanza, PhD Alex Vasquez, BS
[email protected] Biotics Research Corporation Rosenberg, Tex John Cannell, MD Atascadero, Calif William P. Grant, PhD Newport News, Va 1. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA. 2004;292:65-74. 2. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362-371. 3. McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med. 1992;93:69-77. 4. Dubbelman R, Jonxis JH, Muskiet FA, Saleh AE. Age-dependent vitamin D status and vertebral condition of white women living in Curacao (The Netherlands Antilles) as compared with their counterparts in The Netherlands. Am J Clin Nutr. 1993;58:106-109.
In Reply: We appreciate the responses of Drs Alekel, Sirtori, and Muanza and colleagues to our study. Regarding Alekel’s methodological concerns, although the general assumption ©2004 American Medical Association. All rights reserved.
was that isoflavones are as effective as hormone therapy, for BMD power calculations we used data previously reported from an intervention that was quite similar to ours for an even shorter duration that included smaller groups of women.1 When we calculated that 200 participants were needed for this study, this calculation took into account a dropout rate of 25% for all women, for an eventual number of 75 participants in each intervention group, which is the number needed for the secondary per protocol analysis. The sample-size calculations were 2-sided and in agreement with the above assumptions. Our statistical adjustment for smoking history included current smoking and did not change the results. Additional adjustment for the use of antihypertensive medication also did not change our findings. As we noted in our discussion, we agree that the timing of the intervention in relation to onset of menopause might be critically important. Although the exclusion of 12 scans does decrease power, our modified intention-totreat analysis still reached the pre-calculated numbers of 75 scans per treatment group. Finally, compliance, defined as use of more than 80% of supplements, was 96% in the soy group and 94% in the placebo group. With respect to Dr Sirtori’s comments, we did not conclude that soy proteins have no effect on plasma lipid levels. Rather, the results of our study do not support the hypothesis that isoflavones from soy protein have beneficial effects on plasma lipid levels and other variables in older postmenopausal women. This finding is supported by several other reports.2-5 The concern of Dr Muanza et al that vitamin D intake may have been inadequate in our population is unwarranted. Although the participants’ regular vitamin D intake from food decreased from 4.27 µg/d (171 IU) to 3.54 µg/d (142 IU) during the intervention, both the soy and the placebo supplement contained 800 IU of vitamin D per sachet, so that the participants’ intake was very close to the suggested daily intake of 1000 IU. We therefore do not believe that inadequate vitamin D intake explains our null findings. Yvonne T. van der Schouw, PhD
[email protected] Diederick E. Grobbee, MD, PhD Linda Kok Sanne Kreijkamp-Kaspers University Medical Center Utrecht Utrecht, the Netherlands 1. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. 1998;68(6 suppl):1375S-1379S. 2. Dent SB, Peterson CT, Brace LD, et al. Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors. J Nutr. 2001;131:2280-2287. 3. Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J Clin Endocrinol Metab. 2002;87:118-121. 4. Nestel PJ, Yamashita T, Sasahara T, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol. 1997;17:3392-3398. 5. Gardner CD, Newell KA, Cherin R, Haskell WL. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr. 2001;73:728-735. (Reprinted) JAMA, November 17, 2004—Vol 292, No. 19 2337
