Commentary by Dr. G. Bartlett: Metabolic Syndrome and HIV

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Literature Commentary by Dr. G. Bartlett: Metabolic Syndrome and HIV, January 2008

G. Bartlett, MD Medscape HIV/AIDS. 2008; ©2008 Medscape

Posted 01/08/2008

Mondy K, Overton ET, Grubb J, Tong S, Seyfried W, Powderly W, Yarasheski K. Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. Clin Infect Dis. 2007;44:726-734. The authors address the issue of highly active antiretroviral therapy (HAART) and the possible association with increased risk of the metabolic syndrome and the risk of cardiovascular disease.

Methods: The authors, from Washington University School of Medicine in St. Louis, conducted a prospective, cross-sectional study of risk factors associated with the metabolic syndrome and cardiovascular disease in outpatients with HIV infection. The analysis included a total of 601 patients who were assessed for the metabolic syndrome, defined as at least 3 of the following[1]:

Abdominal obesity: waist circumstance > 102 cm for men and > 88 cm for women;

Fasting triglyceride level ≥ 150 mg/dL;

hHigh-density lipoprotein (HDL) cholesterol < 40 mg/dL for men and < 50 for women;

Fasting blood glucose 100-125 mg/dL;

Blood pressure ≥ 130/85 mm Hg or medication for high blood pressure (HBP); and

Obesity: body mass index (BMI) - wt (kg)/height2 (cm) ≥ 30.

The results were assessed by comparison with matched control patients from the National Health and Nutrition Examination Survey (NHANES.) The comparison included 471 HIV-infected patients with complete data and 471 controls without HIV infection. The analysis was also done for 120 patients with HIV infection with the metabolic syndrome vs 351 with HIV who did not meet the criteria for the metabolic syndrome.

Results: The overall prevalence of the metabolic syndrome was similar for those with and without HIV infection, with rates of 25.5% vs 26.5%, respectively. The comparison of those with and without the metabolic syndrome from the group with HIV infection showed that those with the metabolic syndrome were more likely to be diabetic, older, white, and to have a high CD4+ cell count and an increased BMI. Of significance is the observation that the type or duration of antiretroviral therapy was not identified as an independent risk factor. Although the overall prevalence was almost identical for patients with, vs those without HIV infection, the components of the metabolic syndrome were different: smaller waist circumference, lower BMI, lower low-density lipoprotein cholesterol levels, higher triglyceride levels and lower glucose levels were seen in the patients with HIV infection. Table 1 shows the data comparing HIV-infected patients with and without the metabolic syndrome. Table 2 shows the comparison of those with and without HIV infection.

Conclusion: The authors conclude that the prevalence of the metabolic syndrome among patients with HIV infection is not higher than those without HIV infection and that the risk factors for this complication are unrelated to HAART, but are the "traditional risk factors."

Comment: This is an extraordinarily comprehensive report on an important issue in HIV management: whether HIV disease or HAART increases the risk of cardiovascular disease. The results appear to show neither HIV nor HAART are associated with an enhanced risk of the metabolic syndrome.

An editorial review[2] of this report is provided by Clara from Tufts University who points out that one of the great strengths of the study is the fact that it used an unselected, demographically mixed HIV-infected population and that the control subjects were from a national cohort that has been particularly well studied. She points out that although the overall rate of the metabolic syndrome was not increased with HIV infection: (1) the high prevalence of lipid abnormalities has been reported in many studies as well as here; (2) the lower glucose levels compared with the NHANES cohort was unexpected; (3) others have also found that HAART was not associated with increased rates of the metabolic syndrome, but separate analysis of those receiving lopinavir or didanosine did show a significant risk;[3] and (4) both studies show HIV infection was associated with low levels of HDL cholesterol levels and high triglyceride levels compared with the NHANES cohort. The question posed in this editorial concerns the utility of screening for metabolic syndrome in patients receiving HAART. The conclusion is that there is little support for such screening for any demographic group or for any particular HIV regimen. Nevertheless, some studies, including a recent comprehensive review by Kamin and Grinspoon[4] have shown a small but significant increased risk for cardiovascular disease related to HIV infection and PI-based HAART. This is also a conclusion of the recent report from the D:A:D Study Group based on their prospective observational study of 23,437 patients.[5]

Table 1. Characteristics of HIV-positive Patients With and Without the Metabolic Syndrome

Parameter

Metabolic Syndrome

Yes n = 120

No n = 351

Age (mean)

43 years

39 years*

Sex -- Men

80 (67%)

224 (64%)

Women

40 (33%)

127 (36%)

Race* -- Black

62 (53%)

226 (66%)

White

54 (47%)

117 (34%)

Duration HIV infection (mean)

8.6 years

7.4 years

Viral load < 400 HIV RNA copies/mL

69 (79%)

203 (80%)

Treatment -- NNRTI

49 (41%)

144 (41%)

Unboosted PI

5 (4%)

25 (7%)

Boosted PI

38 (32%)

97 (28%)

Current CD4+ count

542 ± 27

417± 14*

Mean BMI

31

26*

*P < .05; BMI = body mass index; boosted PI = ritonavir boosted protease inhibitor; NNRTI = nonnucleoside reverse transcriptase inhibitor; PI = protease inhibitor

Table 2. Characteristics of HIV-positive and Matched Control HIV-negative Patients With and Without the Metabolic Syndrome

HIV Infection

Odds Ratio

Yes n = 471

No n = 471

Diagnosis: metabolic syndrome

120 (26%)

125 (27%)

Not applicable

Race: black

288 (61%)

288 (61%)

Not applicable

Increased waist circumference

128 (31%)

207 (44%)*

0.5

Low HDL cholesterol

205 (44%)

141 (30%)

1.8

Elevated FBS

102 (22%)

144 (31%)*

0.6

Elevated triglycerides

208 (44%)

119 (25%)*

2.4

Lipid-lowering agent

44 (9%)

23 (5%)*

2.0

*P <.001; FBS = fasting blood sugar; HDL = high-density lipoprotein

References

Bruno R, Gazzaruso C, Sacchi P, et al. High prevalence of metabolic syndrome among HIV-infected patients: link with the cardiovascular risk. J Acquir Immune Defic Syndr. 2002;31:363-365. Abstract CY. Editorial commentary: metabolic syndrome in HIV-infected patients: no different than the general population? Clin Infect Dis. 2007;44:735-738. son DL, Tang AM, Spiegelman D, et al. Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey). J Acquir Immune Defic Syndr. 2006;43:458-466. Abstract Kamin DS, Grinspoon SK. Cardiovascular disease in HIV-positive patients. AIDS. 2005;19:641-652. Abstract The DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723-1735. Abstract

G. Bartlett, MD, Professor of Medicine, s Hopkins University School of Medicine, Baltimore, land; Director, HIV Care Program, s Hopkins Hospital, Baltimore, land

Disclosure: G. Bartlett, MD, has disclosed that he has served on the HIV advisory board for Bristol-Myers Squibb and Abbott. Dr. Bartlett has also disclosed that he has served on the antimicrobial advisory board for Pfizer and the advisory board for & . Dr. Bartlett has also disclosed that he has received a research grant from Gilead.

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