Elite controllers – HIV-positive individuals who maintain undetectable viral loads in the absence of treatment – were hospitalised more frequently than people with HIV who control the disease with antiretroviral therapy, according to new data. The association mainly appears to be driven by a higher rate of cardiovascular hospitalisations among elite controllers.
A Healio report notes that according to the data, however, elite controllers had a lower rate of non-Aids-defining infections. Dr Trevor A Crowell, a research physician with the US Military HIV Research Programme and assistant professor of medicine at the Uniformed Services University of the Health Sciences, and colleagues evaluated adults with HIV and CD4 counts of 350 cells/mm3 or more, and compared the rates of hospitalisation among elite controllers, people medically controlled with ART, patients with low viremia and patients with high viremia (using a threshold of 1,000 copies/mL). They used data from 11 sites in the HIV Research Network, and the analysis included 23,461 individuals from 2005 to 2011. The analysis included 64,290 person-years of observation.
There were 149 confirmed elite controllers in the study, which makes it one of the largest published cohorts of elite controllers, Crowell said. Among the remaining participants, 9,226 were medically controlled, 12,044 had low viremia and 12,847 had high viremia. Of the 8,456 hospitalizations among participants, the elite controllers had the highest all-cause hospitalisation rate: 23.3 hospitalizations per 100 person-years. By comparison, there were 16.9 hospitalisations for high viremia patients, 12.6 for low viremia patients and 10.5 for medically controlled patients.
In a multivariable analysis, elite control was associated with a higher hospitalisation rate compared with medical control (adjusted IRR=1.77; 95% CI, 1.21-2.6). The rate of cardiovascular hospitalisations (aIRR=3.19; 95% CI, 1.5-6.79) and psychiatric hospitalisations (aIRR=3.98; 95% CI, 1.54-10.28) were higher among the elite controllers vs. medically controlled patients. Elite controllers experienced with a lower hospitalisation rate due to non-Aids-defining infection (aIRR=0.32; 95% CI, 0.08-1.3) compared with medically controlled participants. However, overall, non-Aids-defining infections were the most common reason for hospitalization, accounting for 24.1% of admissions.
According to Crowell, elite controllers have historically been told they do not require ART because their virus appeared to be suppressed naturally, resulting in relative preservation of the immune system and delayed progression to Aids. However, it is now known that elite controllers have chronic inflammation that is at least partially driven by low levels of viral replication, he said.
New data found that HIV elite controllers demonstrated higher levels of inflammatory markers despite low levels of viremia, says a Healio report. "Recent reports have suggested that elite controllers may have a more inflammatory state and may be at greater risk of coronary atherosclerosis," Dr Jonathan Z Li, assistant professor of medicine at Harvard Medical School and Brigham and Women's Hospital , is quoted as saying. "We found that elite controllers do have higher levels of inflammation despite having low levels of HIV detected in the blood. More research is needed to determine if these patients may benefit from antiretroviral therapy."
Li and colleagues identified 42 elite controllers from the International HIV Controllers Study. They measured inflammation levels in the elite controllers and compared them with those in two cohorts: 80 HIV-suppressed non-elite controllers and 43 HIV-negative individuals. Inflammation was characterized by the presence of 20 soluble markers of inflammation.
There were significant differences between the cohorts in the levels of 15 of the markers – 14 markers where highest among elite controllers, whereas RANTES was the only marker significantly higher among the other two cohorts. The levels of seven inflammatory markers — sCD14, IP-10, IL-4, IL-10, sCD40L, IFN-gamma and GM-CSF — were at least double in the elite controllers compared with either of the two cohorts. The levels of sCD14 and IL-4 were three times as high in elite controllers.
Using partial least squares discriminate analysis modelling, the researchers could differentiate between the cohorts and discern gender differences in inflammation markers. Lastly, the researchers found no association between inflammation markers and either residual viremia or CD4+ counts. Viral load was associated with CD4+ cell decline, but not inflammatory marker levels.
[link url="http://www.healio.com/infectious-disease/hiv-aids/news/online/%7B1dea6dae-89d9-4270-b2a2-7b476fef4673%7D/hospitalization-rates-greater-among-elite-controllers"]Full Healio report[/link]
[link url="http://jid.oxfordjournals.org/content/early/2014/12/15/infdis.jiu809.abstract?sid=25602cd6-26f8-4ded-adf0-d06f86fbd292"]Journal of Infectious Diseases abstract[/link]
[link url="http://www.healio.com/infectious-disease/hiv-aids/news/online/%7Bfb3a945c-f77f-4239-b850-65198f0ac1a5%7D/higher-levels-of-inflammatory-markers-found-in-elite-controllers"]Full Healio report[/link]
[link url="http://ofid.oxfordjournals.org/content/2/1/ofu117.abstract"]Open Forum Infectious Diseases abstract[/link]