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Prevention and Management of HIV-Associated Cardiovascular Disease

November 17, 2014

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Management of HIV-specific CVD Risk Factors

In addition, CVD risk in HIV disease may be reduced by targeting HIV-associated inflammation and immune activation using established anti-inflammatory therapies (such as aspirin), antiretroviral therapy or novel immunomodulatory agents, according to Triant.

Aspirin, which is commonly used to reduce CVD from traditional risk, may also have potential reducing CVD in HIV disease, but studies suggest that aspirin is dramatically underused by people living with HIV who meet the traditional CVD-risk criteria. One paper reported that 31% of people living with HIV met the criteria for using aspirin to reduce CVD risk, but only 1.6% were receiving it. A reasonable clinical strategy, however, is that anyone with low bleeding risk who has known CVD or a high predicted CVD risk, should be taking aspirin.

There are also data to show that aspirin can decrease immune activation and platelet activation in people with HIV but whether it should be used more widely to prevent AMI or stroke in people living with HIV who don't meet the usual criteria for CVD is unclear.


"Interventions targeted at HIV-specific inflammation and immune activation may better reflect pathogenesis and reduce CVD," said Triant.

Antiretroviral therapy, may help since the most direct intervention would be treating the virus itself. Although the START trial will be the first randomized clinical trial to look at the rates of comorbidities including CVD in patients started on early versus deferred antiretroviral therapy, there has already been a paradigm shift in the role of treatment in relation to CVD risk in HIV.

"The CVD-related benefit from virologic suppression and immune reconstitution achieved by treating HIV are thought to outweigh possible proatherogenic effects of individual medications," said Triant.

This change has been reflected in current HIV treatment guidelines. For instance, in 2010, the IAS-USA HIV treatment guidelines, recommended the initiation of antiretroviral therapy specifically for patients with high cardiovascular risk regardless of CD4 count; and the current DHHS HIV treatment guidelines, recommend antiretroviral therapy for all people living with HIV based upon the "growing awareness that untreated HIV infection or uncontrolled viremia may be associated with the development of many non-AIDS defining diseases, including cardiovascular disease (CVD), kidney disease, liver disease, neurologic complications, and malignancy."

So the clinical strategy is now to treat HIV to reduce inflammation, immune activation, and associated cardiovascular risk, but to consider underlying CVD risk when selecting specific antiretroviral medications that may have varying risk.

However, there appears to be a limit to this strategy as treatment intensification seems to have little or no effect in patients who already have suppressed viral loads. For instance, recent studies have found that when raltegravir (Isentress) was added to suppressive treatment, there was no effect on either flow mediated dilatation (FMD) or markers of viral replication.

Novel interventions, immune-modulators, such as using maraviroc (Selzentry, Celsentri) may be an exception to this rule, by virtue of its activity as a CCR5 antagonist, rather than as an antiretroviral. Recent papers in the literature explore its theoretical role in preventing/delaying atherosclerosis, and one study in mice found that maraviroc reduced the atherosclerotic progression by interfering with inflammatory cell recruitment into plaques suggesting that it could have a potential cardioprotective effect in HIV.

Similarly, Triant believes a number of older immune-modulators may have potential for reducing CVD risk in people living with HIV. These include methotrexate, which has been reported to decrease CVD risk in the general population. A randomized controlled trial is currently underway to assess the effect of low-dose methotrexate on inflammatory markers and endothelial function in HIV-positive patients on suppressive antiretroviral therapy. Meanwhile, current data on other immune modulators has been mixed.

Managing Traditional Risk Factors

The other key strategy for fighting CVD in people living with HIV is to manage traditional CVD risk factors (e.g. smoking, diabetes and hypertension) aggressively.

People living with HIV on suppressive ART may lose more years of life due to smoking than HIV.

Triant's recommended clinical strategy for smoking cessation:

  • Apply guidelines for general population to all HIV smokers:
    • Routine screening integrated into HIV primary care
    • Strong, brief, intensive repeated counseling
    • Pharmacologic interventions (varenicline is safe and effective in HIV)
  • Consider systematic approaches to identify HIV smokers and ensure smoking cessation interventions are applied

Diabetes and Hypertension Management

Additionally, Triant suggests using the follow strategy to monitor and manage diabetes and hypertension:

  • Check fasting glucose or HbA1C (glycated hemoglobin) at HIV diagnosis, 1-3 months after starting or changing treatment regimen, and every 6-12 months thereafter
  • Check HbA1C every 6 months in patients with diabetes
  • Diet and exercise intervention recommended:
    • Shown to decrease HbA1C for HIV patients
  • Check blood pressure annually
  • Follow existing 2014 Hypertension Guidelines for general population
    • No HIV-specific guidelines
  • Consider drug-drug interactions
    • Use of some calcium-channel blockers contraindicated with protease inhibitors

  • Discussion

    Many questions remain regarding the optimal management of CVD risk in people living with HIV, such as whether to use statins more broadly, whether immune-modulators will work and whether CVD prevention strategies should be the same in HIV-infected women and patients in resource-limited settings?

    However, it is clear that clinicians should build CVD risk assessment into their clinical practice, start statins in those who qualify, have a low threshold for diagnostic work-ups in their patients living with HIV, treat HIV and manage traditional CVD risk factors.

    "The intensity and consistency of HIV care provide opportunities to prevent and manage chronic disease complications," Triant concluded.

    Read Part 1 to review the context and pathophysiology of cardiovascular disease in people living with HIV.

    Theo Smart is an HIV activist and medical writer with more than 20 years of experience. You can follow him on Twitter @theosmart.

    Copyright © 2014 Remedy Health Media, LLC. All rights reserved.
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