Kaiser Permanente researchers part of consortium that expands evidence base on cancer and HIV
For people newly infected with HIV, there are many health benefits to being diagnosed and placed on antiretroviral therapy (ART) as quickly as possible. New research that followed a large number of people living with HIV over 15 years finds reduced risk of certain cancers is among the benefits of early treatment.
The study pulled together data from nearly 15,000 people diagnosed with HIV between 1996 and 2014 at more than 200 clinical sites in the United States and Canada, including Kaiser Permanente Northern California. Division of Research epidemiologist Michael Silverberg, PhD, MPH, was lead author of the study, published in August in the journal Clinical Infectious Diseases. Division of Research biostatistician Romain Neugebauer, PhD, contributed sophisticated statistical analysis to the study.
The analysis compared people with HIV who started ART within 6 months of entering care with another group who started ART later. The early ART group had 30% lower risk of all cancers, 64% less risk of AIDS-defining cancers (such as Kaposi sarcoma and non-Hodgkin lymphoma), and 59% less risk of any virus-related cancer (including AIDS-defining cancers and others such as anal and liver cancers). The findings are consistent with a previous clinical trial that studied ART and cancer risk. However, this study has a larger sample size, longer-term follow-up, and conclusions about a broader range of cancers with a known viral cause that were prevented with earlier ART initiation.
Silverberg explains the study’s implications.
Q: How does cancer relate to HIV?
Silverberg: Now that treatment is allowing people with HIV to live longer, they are more likely to experience age-related illnesses such as cancer. We have long known that people with HIV have a higher risk of cancer than the general population, in part because of the immune deficiency related to HIV. These patients also tend to have higher rates of smoking and alcohol use, which also increases their cancer risk. As a result, cancer is among the top concerns for HIV patients as they age, and we wanted to better understand the risks of various types of cancer for people living with HIV and how to prevent cancers in this population.
Q: Why are people with HIV more susceptible to certain cancers?
Silverberg: HIV exacerbates the impact of cancers that have a viral component, such as human papillomavirus with anal and cervical cancers, hepatitis with liver cancer, Epstein-Barr virus with non-Hodgkin lymphoma or human herpesvirus-8 with Kaposi sarcoma. Since the early days of the HIV epidemic it was clear that certain cancers that were exceedingly rare in otherwise healthy individuals, were hallmarks of more advanced HIV disease.
Q: What are the important findings of this study?
Silverberg: The unsurprising finding was that if you start therapy early, you have a long-term reduction in the cancers that are traditionally related to HIV. But we also saw a trend over 15 years that some other cancers that can be caused by a virus were also decreased, and that has not been observed previously. The ideal way to answer these questions is with a randomized clinical trial but trials may be limited by sample size and follow-up. Here we used statistical methods using real-world clinical data to make the groups as similar as possible to get a fair comparison between those who started ART earlier versus later.
Q: How might these findings influence diagnosis and treatment of HIV?
Silverberg: The existing medical guidelines are clear: people should get started on therapy immediately after an HIV diagnosis. But there also needs to be more HIV testing so you can identify the virus earlier in the disease. We found that starting therapy within 6 months of diagnosis, just a very short timeframe, had a significant impact on the risk of certain cancers. It’s really critical to follow the guidelines and get people tested and on therapy as soon as they are diagnosed, since even short delays can impact long-term cancer risk.
Q: Tell us more about the consortium that produced this research.
Silverberg: The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) includes 25 cohorts from around the United States and Canada that combine data so that we can answer questions like this. HIV is relatively uncommon compared with diabetes or obesity or cardiovascular disease, and cancer, as an outcome, is also relatively rare. The NA-ACCORD provides large numbers of patients with extended follow-up and detailed clinical data required for answering questions like these. Addressing key questions about cancer and other uncommon outcomes is foundational to this consortium since it’s challenging to address such questions within individual cohort studies.
Q: What other related research are you working on?
Silverberg: We’re also looking at the type of HIV therapy people are taking and its relation to risk of certain cancers. And I’m very interested in the evaluation of outcomes among people with HIV who are diagnosed with cancer. Many of the cancer treatment trials have excluded people with HIV, and it’s unclear if specific cancer treatments have reduced tolerability or efficacy in HIV patients. So there remains a lot of work to do in this area.