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Comparison Between Guideline-Preferred and Nonpreferred First-Line HIV Antiretroviral Therapy

Published Online: June 19, 2014
Stephen S. Johnston, MA; Timothy Juday, PhD; Amanda M. Farr, MPH; Bong-Chul Chu, PhD; and Tony Hebden, PhD
Objectives

To compare antiretroviral therapy (ART) adherence and persistence and total healthcare expenditures in Medicaid-insured patients with human immunodeficiency virus (HIV) initiating preferred or nonpreferred first-line ART based on March 2012 HHS HIV treatment guidelines.

Study Design

Retrospective observational study using Medicaid administrative healthcare claims from 15 states.

Methods

Subjects were HIV patients 18 to 64 years who initiated first-line HIV-related ART between January 1, 2007, and September 30, 2011, with continuous enrollment for 6 months prior to and at least 3 months following ART initiation. Patients were classified as having initiated preferred or nonpreferred ART based on March 2012 HHS HIV treatment guidelines. Outcomes were: ART adherence (proportion of days covered dichotomized at ≥80% and ≥95%), time to ART nonpersistence, and per patient per month (PPPM) total healthcare expenditures. Outcomes were evaluated using multivariable regressions.

Results

Sample included 1979 patients initiating preferred ART regimens and 1614 patients initiating nonpreferred ART; overall mean age was 41 years; 48% of subjects were female. In the multivariable analyses, patients initiating preferred ART regimens had significantly greater odds of adherence ≥80% (odds ratio [OR], 1.38; 95% CI, 1.07-1.77) and adherence ≥95% (OR, 1.26; 95% CI, 1.05-1.51), and a significantly lower hazard of nonpersistence (HR, 0.48; 95% CI, 0.44-0.52). PPPM total healthcare expenditures were numerically lower for patients initiating preferred ART regimens (–$341; 95% CI, –$888 to $255) but the difference was not deemed significant.

Conclusions

This study reinforces the value of HHS recommendations for first-line ART. The potential impact of these findings will grow as more HIV patients become Medicaid-eligible under the Patient Protection and Affordable Care Act.

Am J Manag Care. 2014;20(6):448-455
More than 1 million people in the United States are currently infected with human immunodeficiency virus (HIV).1,2 While there is currently no cure for HIV, antiretroviral therapy (ART) can reduce HIV-associated morbidity and mortality.3 Based on accumulated clinical evidence, the March 2012 HHS guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommend 4 specific “preferred” ART regimens for ART-naïve patients.3 These are: efavirenz/tenofovir/ emtricitabine (EFV/TDF/FTC), ritonavir-boosted atazanavir + tenofovir/emtricitabine (ATV/r + TDF/ FTC), ritonavir-boosted darunavir + tenofovir/emtricitabine (DRV/r + TDF/FTC), and raltegravir + tenofovir/ emtricitabine (RAL + TDF/FTC).

These guideline-preferred ART regimens have been studied in randomized controlled trials and have been shown to confer the benefits of “optimal and durable virologic efficacy, favorable tolerability and toxicity profiles, and ease of use.”3 Comparatively, nonpreferred ART regimens (defined by guidelines as alternative, acceptable, or not recommended) may have “reduced virologic activity, lack of efficacy data from large clinical trials, or other factors (such as greater toxicities, pill burden, drug interaction potential, or need for additional testing).”3 Though the recommendations for preferred ART regimens are unambiguous, real-world evidence suggests that some healthcare providers nonetheless prescribe nonpreferred ART regimens.4,5 While the beneficial clinical aspects of guideline- preferred ART regimens are well described, the extent to which such benefits translate into improved ART adherence and persistence or lower healthcare expenditures in the ‘real world’ setting of routine clinical practice is poorly understood.

Among the various clinical settings in which HIV patients are commonly treated, the Medicaid setting is one of the most important. Medicaid is the largest source of health insurance for HIV patients living in the United States.6 Furthermore, as of January 2014, Medicaid coverage was expanded to cover all Americans with income below 133% of the federal poverty level, a provision of the Patient Protection and Affordable Care Act (PPACA). This change is predicted to significantly expand and improve access to, and quality of care for, HIV patients living in the United States.7-9 Thus, the objective of this study was to compare ART adherence and persistence and total healthcare expenditures in Medicaid- insured HIV patients initiating current guideline-preferred or nonpreferred first-line ART.

METHODS

Setting and Data

The setting of this retrospective observational cohort study was routine clinical practice in a sample of Medicaid programs in 15 states of varying sizes and sociodemographic compositions across the United States. The Medicaid data were drawn from the 2004-2011 Truven Health Analytics MarketScan Multi-State Medicaid Database, which comprises covered inpatient medical, outpatient medical (including lab claims but not lab results), and outpatient pharmaceutical claims and encounter records, along with patient enrollment records and demographic information such as age, sex, and race. During the study period, over 25 million patients were represented in the database. Further public disclosure of identifying information about the state Medicaid programs covered by the database is restricted by confidentiality agreements between Truven Health Analytics and the data-contributing states.

The data contained in the Medicaid database are statistically deidentified and compliant with the Health Insurance Portability and Accountability Act privacy regulations. Therefore, Institutional Review Board approval and written informed consent were not required for this study.

Patients were identified and study variables were constructed from the data using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, Current Procedural Terminology codes, Healthcare Common Procedure Coding System codes, and National Drug Codes (NDCs), as appropriate.

Patient Selection

HIV patients meeting all of the following inclusion criteria were selected into the study sample: initiated HIVrelated ART between January 1, 2007, and September 30, 2011 (the date of ART initiation was designated the index date); aged 18 to 64 years on the index date; had continuous enrollment with pharmacy benefits for 6 months prior to, and for at least 3 months following, the index date. Patients meeting any of the following exclusion criteria were excluded from the study sample: eligible for Medicare; showed evidence of HIV-related ART prescriptions any time prior to the index date, with data extending back to January 1, 2004, being used to check for prior ART use; showed any evidence of pregnancy or hepatitis B infection.

Study Period

The study period comprised an index date, a baseline period, and a follow-up period. As noted above, the date of ART initiation was designated as the index date. This could have been the date of initiation on a single or combination of ART agents. Outpatient prescription claims for HIV-related ART were evaluated during the first 14 days after the index date (index date included) to establish ART regimens. The fixed 6-month period ending on the day before the index date was designated the baseline period. A variable-length period beginning on the index date was designated as the follow-up period. The duration of the follow-up period equaled the number of days from the index date until the first occurrence of (1) a prescription claim for an ART that was not part of the initiated ART regimen; (2) at least a 30-day continuous gap in any agent from the ART regimen (in which case, the end of the follow- up period was set to the last day on which the patient had possession of ART); (3) disenrollment from Medicaid benefits; (4) or the study end date of December 31, 2011.

Classification of Patients’ Initiated ART

Based upon the March 2012 HHS HIV treatment guidelines,3 patients were classified as initiating either guideline-preferred or nonpreferred first-line ART. This classification was applied for all data years and did not vary according to the preferred guidelines during the timeframe in which the patient actually initiated ART. As noted above, the March 2012 guideline-preferred ART regimens were: EFV/TDF/FTC, ATV/r + TDF/FTC, DRV/r + TDF/FTC, and RAL + TDF/FTC.

Outcomes

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Issue: June 2014
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