Hospital Rate Lower in Antiretroviral Controllers Than in Elite Controllers
People who reach an undetectable viral load by taking antiretroviral therapy run a much lower risk of hospital admission than "elite controllers" -- people who have an undetectable viral load without taking antiretrovirals, according to results of a large 2005-2011 study.1 The elite controllers in this study had particularly high hospital admission rates for heart disease and psychiatric illness.
A tiny proportion of HIV-positive people -- called elite controllers -- maintains an undetectable viral load without taking antiretroviral therapy. Although HIV does not multiply in their bodies nearly as rapidly as in most other HIV-positive people, elite controllers do have ongoing inflammation caused by the virus. Research indicates that this low-grade inflammation exceeds levels seen in people who reach and maintain an undetectable viral load by taking antiretroviral therapy. Research also links ongoing inflammation to cardiovascular (heart) disease, infections, and neurologic (nervous system) disorders in people with HIV.
Whether this constant low-level inflammation in elite controllers boosts the risk of hospital admission for AIDS or non-AIDS diseases was not closely analyzed until this study.
How the Study Worked
The study involved HIV-positive people in care at one of 11 centers across the United States at some point from 2005 through 2011. The 11 centers are part of an ongoing study of HIV-positive people called the HIV Research Network (HIVRN). People with consecutive CD4 counts below 350 or a single CD4 count below 200 were not included in the analysis during the time when they had low CD4 counts.
Researchers defined elite controllers as people with 3 or more consecutive undetectable viral loads without antiretroviral therapy on separate days over a period of 12 months or more. The study included three other groups: medical controllers (3 or more consecutive undetectable viral loads on separate days over a period of 12 months or more while taking antiretrovirals), low viremia (all viral loads below 1000 copies while taking antiretrovirals), and high viremia (any viral load above 1000 copies while taking antiretrovirals). ("Viremia" refers to virus detectable in blood.)
To determine hospital admission rates, researchers checked HIVRN records, which include hospital admission and discharge dates. Most of the HIVRN study sites also had data on the reason for hospital admission. The investigators figured all-cause admission rates and cause-specific admission rates as number of admissions per 100 person-years. Cause-specific rates, for example, are admissions per 100 person-years for specific conditions like cardiovascular disease, psychiatric illness, or non-AIDS infection.
The researchers used standard statistical methods to calculate risk of hospital admission for all causes and for specific causes according to viral load status (elite controller, medical controller, low viremia, or high viremia). This type of analysis considers the potential impact of several factors, including age, race, sex, CD4 count, and insurance status.
What the Study Found
The study included 23,461 HIV-positive people in care, of whom 149 were elite controllers. During the study period, 9226 people qualified as medical controllers, 12,044 as low-viremia patients, and 12,847 as high-viremia patients. (The same person could be in two or more of these three groups at different times if their viral load changed during the study period.) Compared with medical controllers, elite controllers were more likely to be women (50.3% versus 25.7%) and black (58.4% versus 40.9%). Median CD4 count when people entered the study was much higher in elite controllers (778) than in medical controllers (481), low-viremia patients (510), or high-viremia patients (482).
During the study period there were 8456 hospital admissions. The hospital admission rate for any cause was highest among elite controllers (23.3 per 100 person-years), followed by high-viremia patients (16.9 per 100 person-years), low-viremia patients (12.6 per 100 person-years), and medical controllers (10.5 per 100 person-years). A rate of 23.3 per 100 person-years means about 23 of every 100 people got admitted to the hospital each year.
Statistical analysis that considers several hospital admission risk factors simultaneously determined that elite controllers had a 77% higher all-cause admission rate than medical controllers -- regardless of whatever other risk factors they had (Figure 1). Compared with medical controllers in this analysis, low-viremia patients had a 34% higher hospital admission rate and high-viremia patients had a 71% higher hospital admission rate (Figure 1). Several other factors independently predicted hospital admission in this analysis -- older age, female sex, injection drug use, lower CD4 count, HIV/HCV coinfection, HIV/HBV/HCV coinfection, more outpatient visits, and Medicaid or Medicare (versus private insurance).
Non-AIDS infections accounted for the highest proportion of hospital admissions overall, 24.1%. But non-AIDS infections explained only 2.7% of hospital admissions among elite controllers. Cardiovascular disease accounted for 13.5% of hospital admissions overall but for 31.1% of admissions among elite controllers. Lung disease accounted for only 4.8% of overall hospital admissions but for 21.6% of admissions among elite controllers.
Statistical analysis that accounted for several hospital admission risk factors determined that elite controllers had more than a 3-fold higher rate of admission for cardiovascular disease than did medical controllers. Compared with medical controllers, elite controllers had a 4-fold higher rate of hospital admission for psychiatric illness, high-viremia patients had more than a 3-fold higher rate, and low-viremia patients had nearly a 2-fold higher rate.
What the Results Mean for You
This large and well-planned study made several important findings about how often and why people with HIV go to the hospital. Perhaps the single most important finding is that people who reach an undetectable viral load with antiretroviral therapy (called medical controllers in this study) get admitted to the hospital significantly less often than elite controllers (people who maintain an undetectable viral load without the help of drugs).
Elite controllers made up less than 1% of people in this 23,461-person study group. In one sense elite controllers might be envied because they keep their HIV under fairly tight control without antiretrovirals, which can be expensive, may cause side effects, and may interact in harmful ways with non-HIV drugs. Although the viral load of elite controllers remains undetectable, we know HIV is still busy in their bodies because they have more inflammation and immune system activation than people without HIV. This study did not directly measure inflammation or immune system activation, but it suggests that even this low-level HIV activity may contribute to diseases serious enough to send people to the hospital. Compared with people who reached an undetectable viral load through antiretroviral therapy, elite controllers had a higher overall hospital admission rate -- and higher rates of admission for cardiovascular (heart) disease and psychiatric illness.
The study also confirmed that reaching an undetectable viral load with antiretroviral therapy is better than having even a low viral load (below 1000 copies) or a high viral load (above 1000 copies). Both a low viral load and a high viral load -- independently of other risk factors -- predicted a higher rate of hospital admission when compared with an undetectable viral load resulting from antiretroviral therapy. Enough strong and safe antiretrovirals are available to allow most HIV-positive people to reach and maintain an undetectable viral load. Taking all your antiretrovirals exactly as instructed by your HIV provider is the key to reaching and keeping an undetectable viral load.
Researchers who conducted this study proposed that the higher hospital admission rate in elite controllers -- partly explained by a higher cardiovascular admission rate -- could reflect ongoing immune system activation and inflammation in elite controllers. Therefore they suggested that elite controllers may benefit from antiretroviral therapy. They also recommend further research to determine whether elite controllers may benefit from antiinflammatory medications like aspirin or statins.
- Crowell TA, Gebo KA, Blankson JN, et al. Hospitalization rates and reasons among HIV elite controllers and persons with medically controlled HIV infection. J Infect Dis. 2015;211:1692-1702.