 |
|
|
| |
Incomplete HIV Control During ART Triples Risk of non-Hodgkin Lymphoma
|
| |
| |
19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
"....Every 100-cell higher current CD4 count lowered the risk 40%....... even low-level viremia (between 50 and 500 copies) probably contributes to NHL risk...... Current viral load between 50 and 500 copies tripled the risk ......The researchers suggested that "further reduction of NHL incidence will depend on early detection of HIV infection, prompt initiation of ART at higher CD4 cell counts and maximal sustained HIV suppression." They proposed that persistent immune dysfunction and B-cell activation may promote lymphoma even in people with well-controlled HIV infection."
Mark Mascolini
A viral load between 50 and 500 copies during antiretroviral therapy (ART) tripled the risk of non-Hodgkin lymphoma (NHL) in a 7700-person US analysis [1]. A higher current CD4 count lowered the risk.
Previous research associated low CD4 count and cumulative viremia with NHL risk, but little was known about risk factors in people taking current potent regimens until this analysis by the CFAR Network of Clinical Systems (CNICS).
The study involved 10,406 HIV-positive people in care since 1996 at eight sites across the United States. Everyone began combination ART and reached a viral load below 500 copies within 1 year; no one had a lymphoma diagnosis before achieving HIV suppression. CNICS investigators calculated NHL incidence (the new diagnosis rate) starting from the date when a person's viral load fell below 500 copies. They calculated incidence both during suppression (until NHL or last follow-up, death, or a rebound above 500 copies) and after suppression (until NHL diagnosis or last follow-up or death).
Most study participants (80%) were men, 57% became infected during sex between men, 53% were white, and median age stood at 39 (interquartile range [IQR] 33 to 46). While 1408 people (14%) had HCV coinfection, 667 (6%) had HBV coinfection. Median year of HIV suppression was 2004, so many of these people began treatment with still-standard regimens.
Median nadir CD4 count stood at 180 (IQR 60 to 290), and median peak pre-ART viral load was 40,000 copies. Median CD4 count at suppression was 310 (IQR 170 to 470). Most study participants (85%) reached a viral load below 50 copies, and 54% had a rebound above 500 copies during follow-up.
NHL developed in 76 people after viral suppression and in 35 during suppression. Incidence after suppression was 15 per 10,000 person-years and during suppression 14 per 10,000 person-years. After suppression NHL incidence was 20 per 10,000 person-years with a nadir CD4 count at or below 50 and 14 per 10,000 with a higher nadir. During suppression NHL incidence was 19 per 10,000 with a CD4 nadir below 50 and 12 per 10,000 with a higher nadir. In comparison, NHL incidence in the general population in 2004-2008 was 2 cases per 10,000 person-years.
CNICS statisticians built a multivariate model that considered age, race, gender, current CD4 count, peak pre-ART viral load, current viral load, current low-level viremia (between 50 and 500 copies), HCV coinfection, and year of viral suppression. In that analysis two factors independently predicted NHL during HIV suppression and three factors independently predicted NHL after suppression:
During viral suppression:
>> Every 100-cell higher current CD4 count lowered the risk 40% (adjusted hazard ratio [aHR] 0.6, 95% confidence interval [CI] 0.5 to 0.8).
>> Current viral load between 50 and 500 copies tripled the risk (aHR 3.0, 95% CI 1.5 to 6.1).
After viral suppression:
>> Every 100-cell higher current CD4 count lowered the risk 30% (aHR 0.7, 95% CI 0.6 to 0.8)
>> White race doubled the risk (aHR 2.1, 95% CI 1.3 to 3.4)
>> Male gender more than doubled the risk (aHR 2.4, 95% CI 1.03 to 5.6)
The CNICS investigators concluded that even low-level viremia (between 50 and 500 copies) probably contributes to NHL risk. And current CD4 count continues to be an independent predictor of NHL, even after statistical adjustment for age, race, and gender.
The researchers suggested that "further reduction of NHL incidence will depend on early detection of HIV infection, prompt initiation of ART at higher CD4 cell counts and maximal sustained HIV suppression." They proposed that persistent immune dysfunction and B-cell activation may promote lymphoma even in people with well-controlled HIV infection.
Reference
1. Achenbach C, Cole S, Kahn J, et al. Incidence and predictors of NHL among HIV+ patients on suppressive ART. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 131.
|
| |
|
|
|
|
|
