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How should clinicians approach non-AIDS defining cancers in aging patients with HIV?
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Multispecialty collaboration needed.
We are beginning to hear as much about the non-AIDS-defining cancers as we once did about the AIDS-defining cancers, if not more so. However, given the effect of HIV pharmacotherapy and its effect on longevity, and the confounding influence of lifestyle risk factors, it is difficult to gauge if and how our approach to non-AIDS-defining cancers should differ from that applied to the general population.
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Recognizing the importance of immunocompetence in holding certain infections and related cancers in check (KSHV, EBV, HPV), it is accepted that untreated HIV sero-positivity plays a role in the development of malignancies considered as AIDS-defining. The disproportionate prevalence of certain non-AIDS-defining cancers among HIV-positive individuals is not as well understood. Further investigation is needed to clarify the role of HIV infection in the development of malignancy that is not AIDS-defining, particularly anal, liver and lung cancers and Hodgkin’s lymphoma. Two areas that deserve further consideration are the possible effects of HIV on the proliferation of cells independently or in consort with other pathogens, and the potential effects of HIV on immune system surveillance and eradication of dysplastic cells. The extent and complexity of cellular dysregulation that occurs in HIV infection is complicated by treatments that alter biochemical pathways outside those they specifically target. Genetic predisposition and lifestyle, neither of which are easily controlled in epidemiological studies, further obscure the picture. Hopefully, research with an aging cohort of older individuals with HIV will help us to better understand if, when and how HIV contributes to cancers that are routinely prevalent at various life stages. Untangling this HIV-cancer Gordian Knot will likely require the sustained efforts of many researchers rather than the decided slash of a single investigator.
One thing is clear — as people with HIV live longer, clinicians can expect to see more patients who develop non-AIDS-defining cancers. Some cancers may prove to be stimulated or exacerbated by HIV, others may reflect the higher incidence seen in the general population as it ages. Whether treatment of malignancy suspected of being related to or exacerbated by HIV will differ significantly from approaches in the general population is another unanswered question.
In the world of the clinician, management of HIV infection is multidimensional and complex, made even more challenging with a diagnosis of cancer, regardless of the underlying mechanism. Management will continue to require the collaboration of generalists and, as needed, clinical experts in oncology, HIV care, organ systems related to specific cancers, geriatrics, symptom management and palliative care. Optimal treatment will entail adapting the evidence base from various disciplines to address needs as they arise, tailoring interventions to address the biological, psychosocial and spiritual issues in a comprehensive well-coordinated plan of care. Thus, as researchers continue to elucidate causal pathways providing a foundation for enhanced prevention and treatment, clinicians must collaborate, sharing current knowledge and acquired expertise to address the ongoing real-life challenges to care and quality of life faced by those with both HIV and cancer.
Ronald J. Walent, RN, PhD, is an assistant adjunct professor in the department of Physiological Nursing, University of California, San Francisco
Stage set for rise in cancer incidence.
Both AIDS-defining cancers and non-AIDS-defining cancers are of concern. However, we have seen the non-AIDS-defining cancers take a more prominent role in the ART era. They have become by far the greatest threat in the wake of successful treatment, and as patients live longer.
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When we see a patient and place them on ART, we can almost confidently tell them that the treatment will be successful — which is about 90% of the time now — and that within the next several months, they will no longer be at risk for opportunistic infections or AIDS-defining cancers. That claim cannot be made yet for the non-AIDS-defining cancers because we do not know the pathogenic mechanism as well. We know for sure that the majority of those cancers are not significantly associated with the degree of immunosuppression, at least as could be inferred by the CD4 count.
So we have predicted the gradual rise of those non-AIDS-defining cancers. Unfortunately, a lot of the research has confirmed this. As HIV patients taking ART continue to survive longer, the stage is set for a much more rapid rise in the incidence of these cancers.
We are only beginning to have answers to whether individuals with HIV on successful treatment are surviving cancers at the same rate of non-HIV populations. Early on in the pre-ART era, it was reported that the survival rates for cancer were not good. However, in the ART era, that is not necessarily the case, for several reasons. The first is that providers may not have been as aggressive in managing these cancers in HIV populations. Whether it was judicious or not, it was estimated that individuals with HIV had limited survival anyway, so, therefore, rigorous treatment was only prolonging the inevitable. Also, it was believed that these patients could not handle the drastic treatments necessary to deal with these cancers. Another problem was that there was late diagnosis of these cancers in HIV patients, which may have biased estimates of survival in this population.
Most patients in the ART era now have a better preserved immune function than before, so they are more likely to have higher survival rates overall than in the pre-ART era. With that in mind, the survival rates of patients with HIV who acquire non-AIDS-defining cancers are approaching rates of non-HIV populations.
Roger Bedimo, MD, MS, Veterans Health Affairs North Texas, University of Texas Southwestern Medical Center, Dallas