In this study, we compared CRP levels in subjects with HIV monoinfection and HIV/HCV coinfection with similarly aged controls. We found that adjusted CRP levels were substantially higher in HIV-monoinfected men compared with control men but that adjusted levels of CRP were similar in HIV-monoinfected and control women. There was no substantial association of CRP levels with ARV therapy, HIV RNA level, or CD4 cell count. We report the novel finding that HIV coinfection with HCV was associated with a 50% lower adjusted CRP level compared with HIV monoinfection in men and women, however.
Our finding that CRP levels are nearly twice as high among HIV-monoinfected men compared with control men may be of clinical importance. Nearly one third of the HIV-infected men had CRP levels >3 mg/L, which would be classified as high risk for CVD by the CDC/AHA guidelines. (The prevalence of CRP levels >3 mg/mL was not accounted for by extremely high levels of CRP [eg, >10 mg/L].) This degree of CRP elevation could be expected to increase cardiovascular risk by 50% based on evidence from the general population,33
although the prognostic role of CRP and CVD in HIV infection has yet to be validated. In women, HIV infection was not associated with substantially higher CRP levels after multivariable adjustment for confounding factors, including adipose tissue volume as measured by MRI. A previous study also found that CRP levels were elevated in HIV-infected women but that HIV was not a factor after adjusting for waist-to-hip ratio.34
That study did not report on the prevalence of HCV coinfection.
Our finding that HCV infection was associated with substantially lower CRP levels among HIV-infected subjects should be interpreted within the context of the cross-sectional design of this study. We cannot prove causality or define a mechanism from this study; however, interesting hypotheses emerge. One possibility is that HCV decreases production of CRP from the liver. In a study of patients on hemodialysis, infection with HCV was associated with a lower CRP/interleukin (IL)-6 ratio.35
This finding suggests a disturbance in the liver’s ability to respond to IL-6 with stimulation of CRP secretion. The concept that HCV prevents secretion of CRP is supported by in vitro studies of expression of HCV proteins in cultured hepatocytes, which causes inhibition of secretion of other liver proteins, such as apo B100,36
a protein whose circulating levels are also decreased in HCV infection.37
The association of HCV with decreased CRP was not affected by adjustment for measures of hepatotoxicity, however, such as levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or albumin.
Our results and those among patients undergoing dialysis have potential clinical implications. Epidemiologic studies suggest an association between HCV infection and increased risk of CVD.37
Our data therefore raise the question as to whether CRP can predict CVD risk differently in patients with HCVor HIV/HCV coinfection. This is an important topic for future study.
A similar discordance has been found in patients with acromegaly, among whom CRP levels are significantly lower than those of controls despite acromegaly’s association with premature cardiovascular mortality.38
CRP levels increase toward the levels of controls when acromegaly is treated, yet the treatment reduces cardiovascular mortality risk. Conversely, CRP levels are relatively elevated in persons who are deficient in growth hormone and correct with growth hormone replacement therapy.39,40
These findings suggest that CRP may not be as good an indicator of CVD risk in persons with abnormal levels of growth hormone, because these conditions affect CRP independent of inflammation and atherosclerosis. Whether HCV infection poses a similar obstacle to the use of CRP as a cardiovascular risk factor awaits additional investigation.
The strengths of this study include a large population-based HIV cohort; a control group of similar age, gender, and racial composition; and the use of MRI for body composition analysis, which allowed important multivariable adjustments. This study does, however, have certain limitations, especially its cross-sectional design, which limits the ability to evaluate the direction and causality of the reported associations. Clearly, CRP levels could not have caused HIV and HCV infection; however, we cannot determine whether the participants with HIV and HIV/HCV coinfection would have had different CRP levels compared with the controls before their infection. Although we adjusted for other determinants of CRP levels, we cannot exclude the possibility of residual confounding. In addition, we may have had insufficient statistical power to detect associations of ARV use with CRP levels, particularly for agents that were used infrequently.
In conclusion, this study found that HIV/HCV coinfection was associated with substantially lower CRP levels among HIV-infected men and women. Only men with HIV monoinfection had substantially higher CRP levels than controls. Future epidemiologic studies should evaluate carefully the association of CRP with CVD in HIV-monoinfected and HIV/HCV-coinfected persons.