Chronic Illness and Multimorbidity

1. Risk Factors for Short-Term Virologic
Outcomes among HIV-infected
Patients undergoing Regimen Switch of
Combination Antiretroviral Therapy
Chun Chao1, Beth Tang1, Leo Hurley2, Michael J Silverberg2, William Towner3, Melissa
Preciado1, Michael Horberg4
Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
1
Division of Research, Kaiser Permanente Northern California, Oakland, California
2
Los Angeles Medical Center, Kaiser Permanente Southern California, Los Angeles, California
3
Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic, Rockville, Maryland
4
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2. Introduction
 The therapeutic management of HIV+ patients involves
the balance of maintaining maximally controlled HIV
RNA levels and high CD4 T cell counts, while
minimizing adverse effects.
 Current treatment guidelines for HIV patients advocate
targeting maximal viral control and early regimen switch
in the event of treatment failure.
 However, not all patients are able to achieve and
maintain HIV RNA level below the assay’s lower limits
of quantification.
 Failure to achieve maximal viral suppression poses
challenges to the clinical management of HIV+ patients.
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3. Introduction (cont.)
 Information on predictors of virologic outcome
among treatment experienced patients therefore
would be helpful for clinicians considering regimen
changes.
 Previous studies reported that several factors may
influence the likelihood of achieving maximal viral
control after switching regimens,
◦ E.g., demographics, previous virologic response, previous
exposure to antivirals, and medication adherence.
◦ Racial disparity has been observed in HIV treatment
outcomes.
 However, many studies did not separately examine
failing with low level viremia (LLV) from advanced
virologic failure.
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4. Objective
 In this study, we investigated risk factors for
advanced virologic and for LLV among HIV+
patients who underwent cART regimen
switch in Kaiser Permanente California
health plans.
 We examined the role of
◦ Demographics;
◦ HIV disease factors,
 E.g., CD4 cell count, prior AIDS diagnosis, and
antiretroviral regimen-level factors
◦ Novel patient-level factors
 i.e., co-morbidity and healthcare utilization.
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5. Methods
 Study population:
◦ HIV+ persons age 18 and older who underwent a combination
antiretroviral therapy (cART) regimen switch between January
2001 - June 2008 at Kaiser Permanente Northern and Southern
California.
 Regimen switch defined as changing of at least 2 antiretroviral medications.
 For each person, first regimen switch that met the
following criteria was included in the analysis:
◦ ≥ 6 months of prior health plan membership;
◦ ≥ 6 months on the newly switched regimen, i.e., the stabilization
period, without switching to another regimen;
◦ At least one HIV RNA measurement to allow assessment of
virologic response on the new regimen.
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6. Outcomes of interest
 The outcomes of interest were
◦ Achieving maximal viral suppression
 defined as HIV RNA <75 copies/mL;
◦ low level viremia (LLV)
 defined as 75≤HIV RNA≤5000 copies/mL;
◦ Advanced virologic failure
 defined as HIV RNA >5000 copies/mL
at 6 months (+/- 8 weeks) after initiating the
new regimen.
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7. Study design diagram
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8. Covariates of interest
 The following covariates measured at time of regimen
switch were examined as potential risk factors for failing
on the new regimen:
◦ Demographic characteristics,
 Age, gender, race/ethnicity, and public insurance (Medicare and Medicaid) status;
◦ HIV disease factors
 HIV transmission risk group, years of known HIV infection in KP, prior AIDS-
defining diagnosis and CD4 cell count at time of regimen switch;
◦ cART use history
 Known years of cART use at KP, HIV genotyping done immediately prior to
regimen switch (yes/no), ART class of the new regimen, number of cART
regimens ever taken and virologic failure at the previous regimen;
◦ Other patient-level factors
 History of cardiovascular disease, hypertension, diabetes mellitus, obesity,
hepatitis B and C infection, and non-AIDS defining cancer;
 Healthcare utilization, such as number of office visit, emergency room visit and
hospitalization in the 6 months prior to regimen switch
◦ Calendar year of the regimen switch
◦ cART adherence to the newly switched regimen during the 6
months stabilization period.
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9. Data collection
 All data were collected electronically
from Kaiser Permanente Northern and
Southern California’s electronic health
records and HIV disease registries.
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10. Statistical analyses
 We calculated the distributions of covariates by
HIV virologic response on the new regimen.
 Crude and adjusted associations between
covariates and HIV virologic response were
evaluated in logistic regression models.
◦ Age, gender, race/ethnicity, KP region (northern or
southern California), HIV transmission risk group, and
cART class of the new regimen were specified a priori
to be included in the multivariable analysis.
◦ In addition, covariates that demonstrated a p-value
<0.10 in the univariate analysis were included in the
final model.
◦ We also conducted stratified analysis by CD4 cell
count at regimen switch of <200/µL and ≥200/µL.
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11. Results
 We identified a total of 4,847 HIV+ patients at
Kaiser Permanente California who were of age 18
years or older and had a cART regimen switch
between 2001 and 2008. After the exclusion, a
total of 3447 subjects were included in the study.
 At the end of the stabilization period, 2608 (76%)
subjects achieved maximal viral suppression, 420
(12%) failed with LLV and 419 (12%) experienced
advanced virologic failure with HIV RNA >5000
copies/mL.
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12. Subject characteristics
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13. Crude analyses
 Those who developed treatment failure
on the new regimen were on average
younger, more likely to be racial/ethnic
minority, and more likely to be Medicare/
Medicaid enrollees.
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14. Multivariable results
 Younger age was associated with both advanced
virologic failure and failing with LLV on the new
regimen.
 Subjects who were heterosexual [OR=1.56
(0.99-2.46), compared with MSM], as well as
those with lower CD4 cell count [OR=0.82
(0.76-0.89) per 100/mm3 increase] had elevated
odds of developing advanced virologic failure.
 Advancement in calendar year was associated
with decreased likelihood of treatment failure.
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15. Multivariable analysis results
 cART-regimen level factors:
◦ Comparing with PI-based regimens, NRTI-only regimens
were associated with both failing with advanced virologic
failure and with LLV.
◦ New class- and mixed class-based regimens, on the other
hand, appear to be protective for failing with LLV.
◦ As expected, virologic failure at previous regimen was a
strong risk factor for failing the new regimen
 Odds Ratio (OR)=4.71 (2.84-7.81) for advanced failure
 OR= 3.15 (2.17-4.57) for LLV
◦ Greater medication adherence to the new regimen was
protective for treatment failure
 OR=0.96 (0.95-0.97) for advanced failure per 1% increase in
adherence
 OR=0.97 (0.96-0.98) for LLV per 1% increase in adherence
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16. Multivariable analyses
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17. Multivariable analyses (cont.)
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18. Stratified analyses
 When we repeated the analyses stratified by
CD4 cell count at regimen switch, the same risk
factors were identified for treatment failure
among the group with CD4 cell count <200/µL
and the group with CD4 cell count ≥200/µL.
 However, among those with CD4 cell count of
200/µL and higher, new class-based cART
regimen was also protective for advanced
virologic failure when compared with PI-based
regimen
◦ OR=0.29 (0.09-0.93) for advanced virologic failure
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19. Summary of findings
 Among a treatment-experienced HIV-infected patient
population undergoing regimen switch,
◦ about 24% failed to achieve maximal viral suppression after 6
months on the new regimen.
 12% experienced advanced virologic failure.
 Younger age, heterosexual patients compared with MSM,
lower CD4 cell count, NRTI-only regimens compared with
PI-based regimens, and previous virologic failure remained
independent risk factors for advanced virologic failure.
 cART regimens based on new class or mixed class was
protective for failing with LLV.
 Rates of treatment failure decreases as calendar year
advanced.
 In the multivariable analyses, racial/ethnic minorities or
patients with public insurance did not have elevated risk of
adverse virologic outcomes after regimen switch.
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20. Limitations and Strengths
 Limitations
◦ There was no standardized follow-up visits: a considerable
proportion of eligible patients (21%) were excluded due to
the lack of an HIV RNA measurement to determine
virologic response on the new regimen.
◦ Information on reasons for changing regimens for each
individual was not available from electronic medical
records.
◦ We only assessed short-term virologic response on the
new regimen.
 Strengths
◦ A well-defined, racial/ethnically diverse patient population
◦ A comprehensive clinical record system that allow detailed
assessment of each patient’s’ clinical history.
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21. Conclusion
 These findings point to the importance of the
choice of the new regimen, as well as
maintaining CD4 cell count and maximal viral
suppression.
 The risk factors identified in this study should
be taken into consideration when considering a
change of antiviral treatment and the
subsequent patient care plan.
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