HIV-infected elite controllers require more hospitalizations

Last Updated: 2015-01-01

By Will Boggs MD

NEW YORK (Reuters Health) - Elite controllers require more hospitalizations than do medically controlled HIV-infected patients, according to findings from the HIV Research Network.

"This study adds to the growing body of evidence suggesting that elite control of HIV infection is inferior to medical control of HIV infection with antiretroviral therapy. Patients and healthcare providers should consider starting antiretroviral therapy in the setting of elite control," Dr. Trevor A. Crowell from Johns Hopkins University School of Medicine in Baltimore, Maryland told Reuters Health by email.

Elite controllers somehow manage to suppress their HIV infections, but they still have chronic immune activation and low-grade inflammation that may contribute to their higher risk of cardiovascular disease.

Dr. Crowell and colleagues in the HIV Research Network used data from 23,461 individuals (including 149 chart-confirmed elite controllers) to compare hospitalization rates among elite controllers with those of immunologically intact individuals with medically controlled and uncontrolled HIV infection.

All-cause hospitalization rates were highest for elite controllers (23.3 hospitalizations per 100 patient-years), followed by patients with high viremia (16.9), patients with low viremia (12.6), and patients with medical control (10.5), the researchers reported online December 15th in The Journal of Infectious Diseases.

In the multivariable model, elite controllers were 77% more likely than medically controlled patients to require hospitalization. Other factors independently associated with hospitalization included older age, female gender, IV drug use, lower CD4 count, coinfection with HIV and hepatitis C virus (HCV), HIV/HCV/HBV tri-infection, more outpatient visits, and Medicaid or Medicare insurance (versus private insurance).

Among elite controllers, the most common reasons for hospitalization were cardiovascular disease (31.1% of admissions) and pulmonary disease (21.6%), whereas non-AIDS-defining infections accounted for only 2.7% of admissions (compared with 24.1% of admissions for the entire study group).

"Historically, antiretroviral therapy was much more toxic and difficult to use than it is today," Dr. Crowell explained. "Because elite controllers naturally experience the immune preservation and delayed disease progression that is the principal goal of antiretroviral therapy, they have long been told that this therapy was unnecessary and its risks outweighed its benefits. Today, there are many well tolerated and easy-to-use options available for antiretroviral therapy. We also now understand that elite control of HIV comes at the cost of chronic inflammation. It is possible that the benefits of antiretroviral therapy for elite controllers may now outweigh the minimal risks associated with therapy."

"Studies to investigate various treatments among elite controllers are ongoing," he said. "In order to provide the best possible care to elite controllers, we must learn how to mitigate the adverse effects associated with chronic inflammation and immune activation while preserving the otherwise beneficial effects of elite control."

If the inflammation notion is correct, would elite controllers be better treated with anti-inflammatory therapies or with antiretrovirals? "Ongoing studies will provide valuable insights, but it is unlikely that we will ever have a definitive answer" to that question, Dr. Crowell said.

"It is just too hard," he added, "to conduct the requisite large, randomized trials to evaluate clinical endpoints in a population as rare as elite controllers."

"Elite control has historically been cited as a model for a potential 'functional cure' of HIV," Dr. Crowell concluded. "A functional cure of HIV should equal or exceed the benefits to infected patients that can be achieved with antiretroviral therapy. Elite control does not do this. Elite control offers clues toward how we might achieve a functional cure of HIV, but ultimately we must strive for something better."

Drs. Maile Y. Karris and Richard H. Haubrich from the University of California San Diego wrote an editorial related to this report. Dr. Karris told Reuters Health by email, "In general persons living with HIV have higher levels of ongoing inflammation than HIV-uninfected people which is believed due to multiple factors (HIV replication or microbial translocation). Of these factors, ongoing HIV replication is the greatest driver of inflammation - so antiretroviral therapy is beneficial to diminish 'inflammation' as well as CD4 T cell recovery/preservation."

"In elite controllers (with preserved CD4 T cells and undetectable viremia), the use of anti-inflammatory therapies may offer clinical benefits - but we do not know if the benefit of anti-inflammatory therapy would outweigh potential risks (i.e. gastritis/GI bleeding with aspirin or rhabdomyolysis with statins.) Ongoing (NCT02081638) and planned studies will address this question," she said.

Dr. Olivier Lambotte from Hôpital de Bicêtre, Le Kremlin-Bicêtre, France, principal investigator for the ANRS HIV Controllers cohort, told Reuters Health by email, "There is an abnormal level of systemic inflammation in controllers which is not only dependent of low level of viral replication but also due to other mechanisms as microbial translocation. The use of ARV drugs is helpful but is not sufficient; the use of anti-inflammatory drugs is a major field of interest, and there is a trial with statins at the NIH."

"Controllers should have a careful clinical follow-up as other HIV-infected patients to be able to detect co-morbidities," Dr. Lambotte concluded. "The best strategy of treatment remains to be determined."

SOURCE: http://bit.ly/1svL26C

J Infect Dis 2014.