BACKGROUND

Hepatic steatosis is increasing worldwide. Whether HIV and its associated metabolic perturbations exacerbate steatosis is unclear. Sex differences in adipose tissue distribution may also affect steatosis risk. We examined the contribution of HIV and sex to steatosis.

METHODS

Using MRI and spectroscopy, visceral adipose tissue (VAT) and liver fat fraction (LFF) were measured in 121 HIV-infected and 107 uninfected men and women without viral hepatitis. Differences in LFF by HIV status and sex were evaluated using multivariable linear regression, adjusting for demographic, lifestyle, VAT, homeostasis model assessment-estimated insulin resistance, and HIV-related factors.

RESULTS

HIV-infected women had lower LFF than uninfected women (demographic-adjusted mean: 1.9 vs. 3.1%; P = 0.028); LFF was similar in HIV-infected and uninfected men (4.6 vs. 4.1%; P = 0.78). HIV-infected and uninfected women had less VAT than men (median: 139 and 161 vs. 201 cm and 188 cm, respectively). After adjustment, HIV-infected women had 34% [95% confidence interval (CI): -54%, -5.5%] lower LFF than uninfected women, whereas there was little difference in men (-5.5%; 95% CI: -26%, 21%). Among HIV-infected persons, greater VAT and homeostasis model assessment-estimated insulin resistance were associated with greater LFF. HIV-related factors (CD4 cell count, HIV RNA level, or antiretroviral therapy use) had little association with LFF. Although HIV-infected men had 81% (95% CI: 32%, 148%) greater LFF than HIV-infected women, the association was attenuated after multivariable adjustment (25%; 95% CI: -9.1%, 73%).

CONCLUSION

Contrary to expectation, HIV infection is not associated with greater steatosis compared with uninfected adults. It is possible that less fat is stored in the liver to maintain subcutaneous fat (which is reduced in HIV) and the effect is magnified in HIV-infected women, who also have less VAT.

OBJECTIVES

HIV/hepatitis C virus (HCV) coinfection is associated with insulin resistance, but the mechanism is unclear. We hypothesized that intestinal epithelial damage and the consequent monocyte/macrophage activation and inflammation explain this perturbation.

DESIGN

Cross-sectional study of 519 adults (220 HIV+/HCV-; 64 HIV-/HCV+; 89 HIV+/HCV+; 146 HIV-/HCV-).

METHODS

We used multivariable linear regression to evaluate associations of HIV and HCV with the homeostasis model assessment of insulin resistance (HOMA-IR) and if intestinal fatty (FA) acid binding protein (I-FABP, a marker of gut epithelial integrity), soluble CD14 (sCD14) and soluble CD163 (sCD163) (markers of monocyte/macrophage activation), and IL-6 (an inflammatory cytokine) mediated this association.

RESULTS

HIV+/HCV+ and HIV-/HCV+ had greater demographic-adjusted HOMA-IR [mean (95% confidence interval (CI)): 1.96 (1.51, 2.54) and 1.65 (1.22, 2.24)] than HIV+/HCV- and HIV-/HCV-[1.41 (1.18, 1.67) and 1.44 (1.17, 1.75), respectively]. After additional adjustment for lifestyle and metabolic factors, HIV+/HCV+ remained associated with 36% (95% CI: 4, 80%) greater HOMA-IR relative to HIV-/HCV-, whereas HIV-/HCV+ and HIV+/HCV- had smaller differences. Adjustment for sCD163 substantially attenuated the difference between HIV+/HCV+ and HIV-/HCV-; adjustment for I-FABP, sCD14, and IL-6 had little effect. Higher sCD163 was independently associated with 19% (95% CI: 7, 33%), 26% (95% CI: 15, 39%), 25% (95% CI: 14, 37%), and 23% (95% CI: 11, 36%) greater HOMA-IR in HIV+/HCV+, HIV-/HCV+, HIV+/HCV-, and HIV-/HCV- (all estimates per doubling of sCD163). I-FABP, sCD14, and IL-6 were not associated with HOMA-IR.

CONCLUSION

HIV/HCV coinfection is associated with greater HOMA-IR, even after controlling for demographic, lifestyle, and metabolic factors. sCD163, which appears independent of intestinal epithelial damage and inflammation, partly explains this association. Our findings that the association of sCD163 with HOMA-IR occurred even in the absence of HIV and HCV, indicate that viral and nonviral factors affect sCD163 levels. Its role in insulin resistance needs elucidation.

BACKGROUND

Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention.

METHODS

We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention.

RESULTS

We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women), ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women), ~90% of the benefit of testing all women would be derived.

CONCLUSION

SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.