Among a cohort of male HIV-infected and similar age, race and clinical site HIV-uninfected veterans who met NCEP/ATP III criteria for receiving lipid lowering therapy, HIV infection and HCV infection were significantly associated with a lower receipt of lipid lowering therapy even after adjusting for multiple potential confounders. Among HIV-infected veterans, a high HIV viral load and HCV were also associated with a lower receipt of lipid lowering therapy after adjusting for confounders. The association between HIV, HIV-HCV co-infection and receipt of lipid lowering therapy persisted even when participants with CHD were excluded from the analyses.
and secondary prevention trials25
report a reduction in cardiovascular risk among those treated with lipid lowering therapy who are not infected with HIV, no such data exist among those infected with HIV. Nevertheless, current guidelines recommend the use of lipid lowering therapy because of the dyslipidemia associated with combination antiretroviral therapy.26,27
As presented elsewhere,28
our study concluded that the receipt of lipid lowering therapy was low among those infected with HIV, including those with and without prevalent CHD.
The lower rates of lipid lowering therapy observed among HIV-infected veterans, particularly those with higher viral loads or hepatitis C, may have important implications on the risk of future cardiovascular events. Recent studies involving both HIV-infected and uninfected controls1,2
as well as previous studies from a large health maintenance organization29
suggest that the rates of incident cardiovascular disease events are higher among HIV-infected people as compared with HIV-uninfected people. Whether the increased cardiovascular risk is a function of dyslipidemia associated with antiretroviral therapy is not entirely clear, but the increased risk of cardiovascular disease appears to occur following the initiation of antiretroviral therapy.2,5
Based on results from the SMART study, a non suppressed HIV viral load appears to be an independent predictor of increased CHD risk.30
Similarly, among those who are co-infected with HCV, several studies suggest that HCV may be associated with an increased risk of subclinical31,32
or clinical atherosclerosis33
and HIV-HCV co-infection may be associated with an increased risk of cardiovascular disease.14
Whether less aggressive lipid management contributes to the increased risk of CHD among HIV-infected people, particularly those with higher viral loads or co-infection with hepatitis C, is not known.
The disparity in receipt of lipid lowering therapy between HIV-infected and similar uninfected veterans suggests that prescribing of lipid lowering therapy may play an important role in CVD risk among those infected with HIV. These data do not provide a clear rationale for this disparity. Possible explanations include a ‘learning curve’ in terms of implementing cholesterol treatment guidelines among those infected with HIV combined with the high prevalence of liver disease (i.e., hepatitis C) among those infected with HIV. In this study, clinics associated with lower receipts of lipid lowering therapy also had the highest prevalence of hepatitis C. The potential drug–drug interactions between antiretroviral therapy (ART) and lipid lowering medications may also be partially responsible. In the present study, ART was associated with a lower, but not significant, reduction in the receipt of lipid lowering therapy. Alternatively, HIV providers may be aware of the guidelines for management of dyslipidemia but have adopted the accepted ‘switch the offending drug’ as initial management of dyslipidemia.
The present study has several limitations that warrant comment. First, since our population consisted entirely of male veterans, our results may not be generalizable to women or people outside the Veterans Administration Healthcare System (VAHS). Second, there is the possibility of non-differential misclassification due to participants receiving lipid lowering therapy outside of the VAHS, however, as medications are free or at minimal charge for veterans who are actively receiving care within VAHS clinics, we expect this misclassification to be small. Third, because the NCEP/ATP III guidelines focus on LDL cholesterol, we did not include data on gemfibrozil or other medications used in the treatment of hypertriglyceridemia, a common consequence of some antiretroviral therapy. Fourth, the use of ICD-9 codes, which have been validated by others,10
may have resulted in some misclassification, however, we do not expect this misclassification to be differential. Fifth, as we only had HCV antibody testing, and not viral RNA, we could not account for those individuals who might have had their HCV spontaneously resolve.34
Sixth, there is always the possibility of misclassification of HIV status (i.e., HIV-uninfected participants were actually HIV-infected). However, the likelihood is that this misclassification would only have strengthened the present associations. Other results are possible although not likely. Seventh, as these data were collected in 2001–2002, it is possible that the use of lipid lowering therapy by providers has increased in response to the emergence of CHD in the HIV population. However, the impediments to lipid lowering therapy in the HIV population (e.g., liver disease, HCV, alcohol use) still presently exist. Eighth, we selected the highest cholesterol value when assessing the receipt of lipid lowering therapy. It is possible that some participants may not have been fasting for those levels, but we do not expect this potential misclassification to be differential. Ninth, as a secondary data analysis, we did not have information on the providers’ assessment of the risks and benefits to the patients associated with lipid lowering agents. Lastly, we cannot comment on whether the rates of lipid lowering therapy observed among the HIV-infected veterans are similar to other HIV-infected people who received their care outside the Veterans Affairs Health Care system. However, prior studies have reported that the rates for the receipt of cholesterol screening35
and the level (i.e., quality) of care for hyperlipidemia36
among people receiving their care at Veteran Affairs Medical Centers was higher as compared with nationally representative samples of people receiving care outside the Veteran Affairs Health Care system. Thus we expect our estimated rates to be at least as high as those observed outside the VA system.
In conclusion, we observed that the receipt of lipid lowering therapy among veterans infected with HIV, especially those with high HIV viral loads or co-infected with HCV, was significantly lower as compared with veterans without HIV. This finding, if confirmed in other studies, suggests an important modifiable risk factor for CHD among those with HIV and/or HCV infection.