 |
|
|
| |
Predictors of Overall and Late-Onset Lab Abnormalities With Contemporary Regimens
|
| |
| |
19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
New lab abnormalities grew rarer with greater time on current antiretroviral regimens, according to results of 3500-person US cohort study [1]. When late-onset abnormalities did arise, specific risk factors could be identified. Many of the same variables predicted overall risk of abnormalities. Babafemi Taiwo (Northwestern University, Chicago) and CNICS cohort collaborators believe their findings suggest that lab monitoring can become less frequent in people without early abnormalities.
CNICS combines eight observational cohorts across the United States. This analysis included people starting their first antiretroviral combination at a CNICS site between 2000 and 2010. The investigators excluded people whose initial regimen included didanosine or stavudine and people who had major lab abnormalities before starting antiretroviral therapy (ART). They defined ART as two or more nucleosides plus a protease inhibitor, a nonnucleoside, or an integrase inhibitor.
Significant lab abnormalities assessed included (1, hepatic) aspartate or alanine transaminase at or above 3 times the upper limit of normal or direct bilirubin at or above 2 times the upper limit of normal, (2, hematologic) hemoglobin at or below 10 g/dL, neutrophil count at or below 750/mm(3), platelet count at or below 50 x 10(9)/mL, (3, lipid) non-high-density lipoprotein (HDL) cholesterol at or above 160 mg/dL, and (4, renal) estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73m(2). The investigators estimated time to first abnormality by Kaplan-Meier analysis up to discontinuation or switch of any drug in the regimen, loss to follow-up, death, or 96 weeks.
Among 3516 people starting ART, 83% were men, 44% white, and 36% black. Median age stood at 39 years (interquartile range 32 to 45). Most people (62%) started a nonnucleoside regimen, while 38% started a protease inhibitor. Most regimens (73%) included tenofovir, while most (79%) did not include zidovudine and most (90%) did not include abacavir.
During follow-up the investigators counted 451 hematologic abnormalities, 339 hepatic abnormalities, 114 renal abnormalities, and 451 lipid abnormalities. Incidence of each type of abnormality was much higher in the first 16 weeks of treatment than afterwards:
Incidence of lab abnormalities (per 100 person-years) in first 2 years of an initial antiretroviral regimen:
-- Hematologic: 41.3 before 16 weeks, 5.0 after 16 weeks
-- Hepatic: 23.4 before 16 weeks, 12.5 after 16 weeks
-- Renal: 8.5 before 16 weeks, 1.8 after 16 weeks
-- Lipid: 41.9 before 16 weeks, 26.0 after 16 weeks
Multivariate analysis determined that older age and female gender raised the risk of most types of abnormality, while higher pretreatment CD4 generally lowered the risk and race/ethnicity differed in impact from one type of abnormality to the next. The following list gives hazard ratios (HR) (and 95% confidence intervals) for risk factors for each group of lab abnormality throughout follow-up and after 16 weeks of therapy. A hazard ratio below 1.0 indicates a lower risk:
Hematologic abnormalities:
-- Female gender: overall HR 1.64 (1.26 to 2.13), after 16 weeks HR 1.68 (1.05 to 2.68)
-- Black vs white race: overall HR 1.69 (1.29 to 2.22), after 16 weeks HR 2.54 (1.56 to 4.13)
-- Each 100-cell higher CD4 count: overall HR 0.74 (0.67 to 0.81), after 16 weeks HR 0.88 (0.77 to 1.02, not significant)
-- AIDS diagnosis: overall HR 1.44 (1.12 to 1.85), after 16 weeks not significant
-- Zidovudine: overall HR 1.77 (1.26 to 2.49), after 16 weeks HR 2.04 (1.08 to 3.88)
-- Hepatitis B: overall HR 1.76 (1.13 to 2.72), after 16 weeks not significant
Hepatic abnormalities:
-- Other nonblack race vs white: overall HR 1.40 (1.04 to 1.88), after 16 weeks HR 1.51 (1.00 to 2.27)
-- Each 100-cell higher CD4 count: overall 0.89 (0.82 to 0.97), after 16 weeks HR not significant
-- AIDS diagnosis: overall HR 1.36 (1.03 to 1.79), after 16 weeks HR not significant
-- Hepatitis B: overall HR 2.95 (1.98 to 4.39), after 16 weeks HR 2.28 (1.23 to 4.23)
-- Hepatitis C: overall HR 3.40 (2.59 to 4.46), after 16 weeks HR 3.50 (2.40 to 5.10)
Renal abnormalities:
-- Each decade of age: overall HR 1.86 (1.49 to 2.32), after 16 weeks HR 1.62 (1.15 to 2.27)
-- Female gender: overall HR 1.83 (1.10 to 3.05), after 16 weeks HR 2.31 (1.09 to 4.87)
-- Each 100-cell higher CD4 count: overall 0.77 (0.66 to 0.91), after 16 weeks HR 0.83 (0.66 to 1.04, not significant)
-- Hypertension: overall HR 2.35 (1.49 to 3.69), after 16 weeks HR 2.63 (1.37 to 5.04)
Lipid abnormalities:
-- Each decade of age: overall HR 1.19 (1.08 to 1.32), after 16 weeks HR 1.28 (1.14 to 1.44)
-- Black vs white: overall HR 0.63 (0.50 to 0.79), after 16 weeks HR 0.69 (0.53 to 0.91)
-- Hepatitis B: overall HR 0.39 (0.22 to 0.72), after 16 weeks HR 0.47 (0.24 to 0.93)
-- Hepatitis C: overall HR 0.30 (0.21 to 0.44), after 16 weeks HR 0.21 (0.12 to 0.35)
-- Hypertension: overall HR 1.31 (1.05 to 1.64), after 16 weeks HR 1.33 (1.02 to 1.75)
This analysis identified no significant associations between tenofovir or abacavir and the lab abnormality groups.
Taiwo and colleagues believe their findings suggest "that as time on initial ART increases, monitoring frequency may be reduced in subgroups without early abnormalities." They suggested that "future guidelines should consider frequencies, timing, and predictors of laboratory abnormalities."
Reference
1. Taiwo B, Yanik E, Napravnik S, et al. Laboratory abnormalities following initiation of modern ART in the US, 2000-2010 among the CNICS cohort. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 633.
|
| |
|
|
|
|
|
