Sandra Yin

November 17, 2011

November 17, 2011 (Bethesda, Maryland) — Patients with HIV are living longer and have more comorbidities. A new index could help clinicians determine who might benefit from screening and measure net benefit for a wide range of interventions for an individual patient.

Amy Justice, MD, PhD, professor of medicine and public health at Yale University, New Haven, Connecticut, presented the metric and described how it was developed and how it works here at the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies.

"The suggestion that we should take primary care guidelines...[for] non-HIV-infected individuals and just apply them to HIV-infected individuals is ill advised," Dr. Justice told Medscape Medical News.

This message applies not only to cancer screening, but also to guidelines more generally, she said.

She noted that patients with HIV face an increased risk for several kinds of cancer, including lung, liver, and anal. It can be difficult to estimate life expectancy because differences in this population are exacerbated by hepatitis C infection; higher rates of smoking, alcohol, and drug use; and varying access or adherence to care. Averages, she said, are largely irrelevant. "We need individually tailored estimates to make more appropriate decisions for our patients."

The Veterans Aging Cohort Study (VACS) Index is a clinical index that accounts for organ-system injury from multimorbidity and treatment toxicity, and is designed to guide care decisions.

Multimorbidity — the simultaneous presence of more than 1 chronic medical or psychiatric health condition requiring medical treatment — is a "game changer," she explained. It can increase the benefit of treatment if a screening target exacerbates several conditions, but it can also decrease survival time gained as a benefit of screening. It increases risk for toxicity and introduces competing concerns related to active conditions and primary care guidelines.

The index, which was developed with veterans' data and validated in both North American and Europe, is a predictive tool. Its main inputs are accurate estimates of risk and risk reduction associated with interventions. It is composed of age and data from lab tests, including HIV biomarkers (HIV-1 RNA level and CD4 count) and non-HIV biomarkers (e.g., hemoglobin, hepatitis C, and composite markers for liver and renal injury).

Dr. Justice explained how the index can be applied. Each factor is assigned a number of points. All the points are added up to create a score. A separate column indicates whether a factor can be modified further. One patient's VACS Index score was 39 and his expected 5-year mortality was 18%. He will likely live more than 7 years, and therefore would benefit from colon cancer screening.

If his FIB-4 — a composite index that is an indicator of liver disease — is normalized through alcohol cessation and weight loss, she said, we can lower his score by 6 points and improve his 5-year mortality, to 14% (a 22% risk reduction). "If we eradicate his [hepatitis C virus] infection, we can further reduce his score, to 28, and his 5-year mortality, to 12% (a 33% risk reduction). Normalization of his FIB-4 may also reduce his risk of hepatocellular cancer," she said, which is currently 4 times higher than in HIV-infected individuals with normal FIB-4.

She noted that only a randomized controlled trial will prove that screening and treatment guided by the VACS Index improves outcomes. In addition, the VACS Index does not include all common sources of risk, such as D-dimer and sCD14, which would improve risk classification.

Dr. Justice said she is currently evaluating whether smoking status, average of 3 blood pressure readings, and/or high-density-lipoprotein cholesterol level improve risk classification.

"My takeaway from Dr. Justice's talk is that we need to carefully assess the clinical-care guidelines for HIV-infected people," Eric Engels, MD, MPH, senior investigator at the National Cancer Institute's division of cancer epidemiology and genetics in Bethesda, Maryland, told Medscape Medical News. Risk for cancer has to be viewed in the context of all the other medical issues that physicians have to consider, he said. We don't want to overload providers with guidelines that wouldn't be practical to implement. "We do want to make cancer screening and prevention a priority," he said, "but we have to do it sensibly and in the context of other medical issues."

The VACS Index might help predict mortality, he said. But whether that particular tool or one like it will be useful for targeting patients for cancer screening still needs to be shown. Different tools for each cancer or each clinical outcome might be needed, he said. "That's another layer of refinement that might need to be developed."

Dr. Justice and Dr. Engels have disclosed no relevant financial relationships.

13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI): Abstract P7. Presented November 8, 2011.

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