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Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1: A Randomized, Controlled Equivalence TrialNNRTI-Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

Jeffrey L. Lennox, MD; Raphael J. Landovitz, MD, MSc; Heather J. Ribaudo, PhD; Ighovwerha Ofotokun, MD, MSc; Lumine H. Na, MS; Catherine Godfrey, MD; Daniel R. Kuritzkes, MD; Manish Sagar, MD; Todd T. Brown, MD, PhD; Susan E. Cohn, MD, MPH; Grace A. McComsey, MD; Francesca Aweeka, PharmD; Carl J. Fichtenbaum, MD; Rachel M. Presti, MD, PhD; Susan L. Koletar, MD; David W. Haas, MD; Kristine B. Patterson, MD; Constance A. Benson, MD; Bryan P. Baugh, MD; Randi Y. Leavitt, MD, PhD; James F. Rooney, MD; Daniel Seekins, MD; Judith S. Currier, MD, MSc, for the ACTG A5257 Team*
[+] Article, Author, and Disclosure Information

* For members of the ACTG A5257 Team, see Appendix 1.


From Grady Memorial Hospital and Emory University School of Medicine, Atlanta, Georgia; Center for Clinical AIDS Research and Education and University of California, Los Angeles, Los Angeles, California; Harvard School of Public Health, Brigham and Women's Hospital, Harvard Medical School, and Boston University School of Medicine, Boston, Massachusetts; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University, Baltimore, Maryland; Northwestern University Feinberg School of Medicine, Chicago, Illinois; Case Western Reserve University, Cleveland, Ohio; University of California, San Francisco, School of Pharmacy, San Francisco, California; University of Cincinnati College of Medicine, Cincinnati, Ohio; Washington University School of Medicine, St. Louis, Missouri; The Ohio State University College of Medicine, Columbus, Ohio; Vanderbilt University School of Medicine, Nashville, Tennessee; University of North Carolina School of Medicine, Chapel Hill, North Carolina; University of California, San Diego, School of Medicine, San Diego, California; Janssen Scientific Affairs, Titusville, New Jersey; Merck, Whitehouse Station, New Jersey; Gilead Sciences, Foster City, California; and Bristol-Myers Squibb, New York, New York.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

Financial Support: By the National Institute of Allergy and Infectious Diseases (award UM1AI068636), National Institute of Mental Health, and National Institute of Dental and Craniofacial Research. The protocol received financial support from the ACTG and the Site Data Management Center (grant UM1AI68634), the ACTG specialty laboratories listed in the article, and the 57 clinical research sites. The list of personnel and grant numbers from these clinical research sites are listed in Appendix 2.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1084.

Reproducible Research Statement:Study protocol, statistical code, and data set: Available through written agreement with the Division of AIDS of the National Institute of Allergy and Infectious Diseases.

Requests for Single Reprints: Jeffrey L. Lennox, MD, Professor of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 69 Jesse Hill Jr. Drive SE, Suite 202, Atlanta, GA 30303; e-mail, jlennox@emory.edu.

Current Author Addresses: Dr. Lennox: Emory University School of Medicine, 69 Jesse Hill Jr. Drive SE, Suite 202, Atlanta, GA 30303.

Drs. Landovitz and Currier: University of California, Los Angeles, Center for Clinical AIDS Research and Education, 9911 West Pico Boulevard, Suite 980, Los Angeles, CA 90035.

Dr. Ribaudo: Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115.

Dr. Ofotokun: Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA 30308.

Ms. Na: Center for Biostatistics in AIDS Research, Harvard School of Public Health, 651 Huntington Avenue, FXB-508, Boston, MA 02115.

Dr. Godfrey: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5601 Fisher's Lane, Room 9E49, MSC 9830, Bethesda, MD 20892-9830.

Dr. Kuritzkes: Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Room 449, Cambridge, MA 02139.

Dr. Sagar: Boston University, Evans Biomedical Research Building, 650 Albany Street, Room 647, Boston, MA 02118.

Dr. Brown: Division of Endocrinology and Metabolism, Johns Hopkins University, 1830 East Monument Street, Baltimore, MD 21287.

Dr. Cohn: Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Room 926, Chicago, IL 60611.

Dr. McComsey: Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106.

Dr. Aweeka: University of California, San Francisco, School of Pharmacy, 1001 Potrero Avenue, SFGH 100, San Francisco, CA 94143.

Dr. Fichtenbaum: University of Cincinnati College of Medicine, PO Box 670560, 231 Albert Sabin Way, Cincinnati, OH 45267-0560.

Dr. Presti: Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, MO 63110.

Dr. Koletar: N1137 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210.

Dr. Haas: Vanderbilt Health One Hundred Oaks, 719 Thompson Lane, Suite 47183, Nashville, TN 37204.

Dr. Patterson: University of North Carolina at Chapel Hill, 130 Mason Farm Road, CB 7215, Chapel Hill, NC 27599-7215.

Dr. Benson: University of California, San Diego, 200 West Arbor Drive, MC #8208, San Diego, CA 92103.

Dr. Baugh: Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Room K-10205, Titusville, NJ 08560.

Dr. Leavitt: Merck & Co., PO Box 1000, Mailstop UG3D-30, North Wales, PA 19454-1099.

Dr. Rooney: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404.

Dr. Seekins: 777 Scudders Mill Road, P11-26, Plainsboro, NJ 08536.

Author Contributions: Conception and design: J.L. Lennox, R.J. Landovitz, H.J. Ribaudo, I. Ofotokun, C. Godfrey, D.R. Kuritzkes, M. Sagar, S.E. Cohn, G.A. McComsey, F. Aweeka, R.M. Presti, C.A. Benson, B.P. Baugh, R.Y. Leavitt, J.F. Rooney, D. Seekins, J.S. Currier.

Analysis and interpretation of the data: J.L. Lennox, R.J. Landovitz, H.J. Ribaudo, I. Ofotokun, C. Godfrey, D.R. Kuritzkes, M. Sagar, T.T. Brown, S.E. Cohn, G.A. McComsey, F. Aweeka, R.M. Presti, S.L. Koletar, D.W. Haas, C.A. Benson, B.P. Baugh, R.Y. Leavitt, J.F. Rooney, D. Seekins, J.S. Currier.

Drafting of the article: J.L. Lennox, R.J. Landovitz, H.J. Ribaudo, I. Ofotokun, C. Godfrey, S.E. Cohn, D.W. Haas, D. Seekins.

Critical revision of the article for important intellectual content: J.L. Lennox, R.J. Landovitz, H.J. Ribaudo, I. Ofotokun, C. Godfrey, D.R. Kuritzkes, M. Sagar, T.T. Brown, G.A. McComsey, F. Aweeka, C.J. Fichtenbaum, R.M. Presti, S.L. Koletar, D.W. Haas, K.B. Patterson, C.A. Benson, B.P. Baugh, R.Y. Leavitt, J.F. Rooney, D. Seekins, J.S. Currier.

Final approval of the article: J.L. Lennox, R.J. Landovitz, H.J. Ribaudo, I. Ofotokun, C. Godfrey, D.R. Kuritzkes, M. Sagar, T.T. Brown, S.E. Cohn, G.A. McComsey, F. Aweeka, C.J. Fichtenbaum, R.M. Presti, S.L. Koletar, D.W. Haas, K.B. Patterson, C.A. Benson, B.P. Baugh, R.Y. Leavitt, J.F. Rooney, D. Seekins, J.S. Currier.

Provision of study materials or patients: J.L. Lennox, R.J. Landovitz, I. Ofotokun, D.R. Kuritzkes, M. Sagar, S.E. Cohn, G.A. McComsey, F. Aweeka, C.J. Fichtenbaum, R.M. Presti, S.L. Koletar, K.B. Patterson, C.A. Benson, B.P. Baugh, R.Y. Leavitt, J.F. Rooney, D. Seekins, J.S. Currier.

Statistical expertise: H.J. Ribaudo, L.H. Na.

Obtaining of funding: J.L. Lennox, D.R. Kuritzkes, M. Sagar, G.A. McComsey, F. Aweeka, R.M. Presti, C.A. Benson, B.P. Baugh, R.Y. Leavitt, D. Seekins, J.S. Currier.

Administrative, technical, or logistic support: C. Godfrey.

Collection and assembly of data: H.J. Ribaudo, I. Ofotokun, D.W. Haas.


Ann Intern Med. 2014;161(7):461-471. doi:10.7326/M14-1084
Text Size: A A A

This article has been corrected. The original version (PDF) is appended to this article as a Supplement.

Background: Nonnucleoside reverse transcriptase inhibitor–based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.

Objective: To evaluate 3 nonnucleoside reverse transcriptase inhibitor–sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.

Design: A phase 3, open-label study randomized in a 1:1:1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954)

Setting: 57 sites in the United States and Puerto Rico.

Patients: Treatment-naive persons aged 18 years or older with HIV-1 RNA levels greater than 1000 copies/mL without resistance to nucleoside reverse transcriptase inhibitors or protease inhibitors.

Intervention: Atazanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus combination emtricitabine, 200 mg/d, and tenofovir disoproxil fumarate, 300 mg/d.

Measurements: Virologic failure, defined as a confirmed HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks or greater than 200 copies/mL at or after 24 weeks, and tolerability failure, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity. A secondary end point was a combination of virologic efficacy and tolerability.

Results: Among 1809 participants, all pairwise comparisons of incidence of virologic failure over 96 weeks showed equivalence within a margin of equivalence defined as −10% to 10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinemia. For combined virologic efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at the time of virologic failure was rare but more frequent with raltegravir.

Limitation: The trial was open-label, and ritonavir was not provided.

Conclusion: Over 2 years, all 3 regimens attained high and equivalent rates of virologic control. Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted atazanavir regimen.

Primary Funding Source: National Institute of Allergy and Infectious Diseases.

Figures

Grahic Jump Location
Figure 1.

Study flow diagram.

A total of 114 participants discontinued randomized treatment before virologic failure: 28 in the ATV/r group, 35 in the RAL group, and 51 in the DRV/r group. ART = antiretroviral therapy; ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; RAL = raltegravir.

* 10 participants were excluded for >1 reason.

† Per protocol, participants found to be ineligible were excluded from analysis.

‡ 5 participants never started ART.

§ 4 participants never started ART.

|| Study closure occurred when the last participants completed 96 wk of follow-up.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Cumulative incidence of primary end points and preplanned composite failure.

ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; RAL = raltegravir.

* “As-treated” signifies that a participant's time to virologic failure was censored at the time of the competing event of discontinuation of randomized treatment.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 1.

Pairwise treatment differences in the cumulative probability of virologic failure by week 96.

ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; RAL = raltegravir.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 2.

Pairwise treatment differences in the cumulative probability of tolerability failure by week 96.

ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; RAL = raltegravir.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 3.

Pairwise treatment differences in the cumulative probability of virologic or tolerability failure by week 96.

ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; RAL = raltegravir.

Grahic Jump Location
Grahic Jump Location
Figure 3.

Proportion of participants with an HIV-1 RNA level ≤50 copies/mL over time, with 95% CIs.

Error bars for all panels indicate pointwise 95% CIs at prespecified key study weeks. ART = antiretroviral therapy; ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; ITT = intention-to-treat; RAL = raltegravir. Top. The number of participants contributing data at each time point (the denominator for the proportion) represents the number of participants with an HIV-1 RNA level available for that study week, regardless of status of randomized treatment. The numerator represents the number of participants with an HIV-1 RNA level ≤50 copies/mL; missing evaluations are assumed to be missing completely at random, and loss to follow-up is assumed to be noninformative. Middle. The number of participants contributing data at each time point (the denominator for the proportion) represents the number of participants continuing randomized treatment with an HIV-1 RNA level available for that study week. The numerator represents the number of participants with an HIV-1 RNA level ≤50 copies/mL; missing evaluations are assumed to be missing completely at random, and loss to follow-up is assumed to be noninformative. Bottom. The number of participants contributing data at each time point (the denominator for the proportion) represents the number of participants with the potential for follow-up to that week based on date of randomization. The numerator represents the number of participants with an HIV-1 RNA level ≤50 copies/mL still receiving randomized treatment.

Grahic Jump Location
Grahic Jump Location
Figure 4.

Outcomes at week 96, according to the FDA snapshot definition.

ART = antiretroviral therapy; ATV/r = atazanavir plus ritonavir; DRV/r = darunavir plus ritonavir; FDA = U.S. Food and Drug Administration; RAL = raltegravir.

Grahic Jump Location

Tables

References

Letters

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Comments

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Comment
Posted on October 15, 2014
Giuseppe Lapadula, Andrea Gori
University Milano-Bicocca
Conflict of Interest: None Declared
We read with interest the paper by Lennox and colleagues, who reported in their randomized controlled trial (RCT) that atazanavir/ritonavir discontinuations due to lack of tolerability were significantly more common than darunavir/ritonavir or raltegravir discontinuations. This effect was mainly driven by atazanavir-induced jaundice and hyperbilirubinemia. (1) The study is characterized by an innovative design, in the field of HIV therapy, because patients were allowed to change treatment arm if intolerant to randomized treatment and because the time to discontinuation due to toxicity (as assessed and reported by the treating physician) was used as a predefined tolerability end-point . Although we understand the logic behind this attempt to reproduce “real life” conditions, we question whether this is within the possibilities and the scopes of a RCT.
In clinical practice, changing an antiretroviral regimen is a free and mutual decision of doctors and patients and it is determined by many factors that are not present or accounted for during RCT, such as socio-economics, previous knowledge and experience with the drugs, peer influences, doctor-patient relationship and the availability of all licensed alternative drugs. Last but not least, important determinants of physician prescriptions are patients’ expectations and, even more, doctors’ opinion on patients expectations. (2) The "threshold" of the tolerability of drug-related side effects, therefore, varies not only between patients, but also between doctors and, within the same patient or doctor, may change over time. Also, ascribing a treatment switch to a single cause ("toxicity") can be very difficult and, ultimately, subjective.
For all these reasons, we believe that assessing “discontinuation due to toxicity” as a component of a randomized clinical trial end-point, in the absence of predefined definition of tolerability and toxicity, can be challenging. In this respect, the data on treatment discontinuation rates, obtained from observational cohorts of unselected patients, can be more adherent to reality.


Reference List

(1) Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C et al. Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor-Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1: A Randomized, Controlled Equivalence Trial. Ann Intern Med 2014; 161(7):461-471.
(2) Cockburn J, Pit S. Prescribing behaviour in clinical practice: patients' expectations and doctors' perceptions of patients' expectations--a questionnaire study. BMJ 1997; 315(7107):520-523.


Comment on A5257-Study
Posted on October 28, 2014
Christoph Stephan, M.D.
Goethe-University Hospital
Conflict of Interest: Dr Stephan has served as an advisor, consultant, author, or trustee for: Bristol-Myers Squibb Company; Gilead Sciences, Inc.; GlaxoSmithKline/ViiV Healthcare; Janssen; Merck, AbbVie. Reception of an unrestricted research grant by Merck Sharpe & Dohme (MSD). The author does not own stocks from above companies, has no further relevant affiliations, or financial interests with any specific organizations or entities, and has no financial conflicts with the subject matter or materials, as discussed in the manuscript apart from those disclosed.
A design characteristic allowed patients to switch the third antiretroviral compound within A5257 open label trial – this is distinct from historical randomized clinical comparisons. Aim of this protocol specification may have been to enable antiretroviral therapy switch for patients facing non-serious adverse events, approaching a real-life clinical setting. Prerequisite for an unbiased observation is the free dispense for all administered study drugs. However ritonavir booster (100mg daily) was not provided for participants randomized to a protease inhibitor regimen within the study and it remains unclear how often these costs were finally reimbursed to affected patients. Secondly atazanavir maintenance was most likely disadvantaged by the distinct design characteristic, because cosmetically adverse hyperbilirubinemia had previously not been a typical reason for atazanavir cessation [1-3]. Both empathic physicians and affected patients had an interest to carry out the per-protocol allowed switch towards raltegravir, heading to kill two birds with one stone: saving patient’s money from ritonavir prescription and overcoming atazanavir related hyperbilirubinemia. This circumstance may have been aggravated by preferred recruitment of impecunious, uninsured female patients in advanced study phase, as previously mentioned [4]. Due to these limitations, consequences on treatment guideline modifications should be drawn with caution.

References:
[1] Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet 2008;372(9639):646-55
[2] Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL, Garren KW, George T, Rooney JF, Brizz B, Lalloo UG, Murphy RL, Swindells S, Havlir D, Mellors JW; AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med 2008;358(20):2095-106
[3] Daar ES, Tierney C, Fischl MA, Sax PE, Mollan K, Budhathoki C, Godfrey C, Jahed NC, Myers L, Katzenstein D, Farajallah A, Rooney JF, Pappa KA, Woodward WC, Patterson K, Bolivar H, Benson CA, Collier AC; AIDS Clinical Trials Group Study A5202 Team. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. Ann Intern Med 2011;154(7):445-56
[4] Sax PE, Landovitz RJ. Selecting an Initial ART Regimen: Lessons From ACTG 5257. Medscape. Apr 11, 2014 see http://www.medscape.com/viewarticle/823164 (last accessed June 23rd, 2014)
Reply to Stefan, Lapadula and Gori
Posted on November 20, 2014
Jeffrey L. Lennox MD, Raphael J. Landovitz MD MSc, Heather Ribaudo PhD PhD
Grady Memorial Hospital and Emory University School of Medicine, Atlanta, GA; Division of Infectious Diseases, Center for Clinical AIDS Research and Education, University of California, Los Angeles,
Conflict of Interest: Dr. Lennox has received research funding from Gilead Sciences and Merck INC, and has served as a consultant to Bristol Myers Squibb and Merck INC. All three authors received funding from the National Institutes of Health in support of this study
Dr. Stefan proposes a potential bias against ritonavir-boosted atazanavir due to the necessity to reimburse ritonavir copayments. He also suggests that efforts to ensure adequate representation of women may have enriched the study for impoverished subjects predisposed to discontinue ritonavir-containing regimens to avoid costs. We did not target any particular socioeconomic subgroup of women for enrollment, nor have we suggested that we did so. The potential biases associated with ritonavir use during the study were anticipated and addressed during trial design. As noted in the manuscript, all participants not receiving their ritonavir from a federal insurance program were reimbursed in a timely manner. Further, the protocol encouraged sites to make within-class regimen switches, resulting in 72% of those who discontinued ritonavir-boosted atazanavir switching to ritonavir-boosted darunavir. Dr. Stephan also cites three studies in which hyperbilirubinemia was not a common reason for atazanavir cessation. One of these studies (A5142) did not include atazanavir. Another (A5202) placed stringent limitations on regimen switching since it was comparing not only ritonavir-boosted atazanavir to efavirenz, but also separate nucleoside reverse transcriptase combinations. The third study (CASTLE) compared a three pill, once daily boosted atazanavir regimen to a six pill, twice daily boosted lopinavir regimen, a design that may have discouraged regimen changes. Our study demonstrates that some subjects who develop cosmetically intolerable hyperbilirubinemia will choose to change therapy if equally effective and convenient options are available.

We agree with Drs. Lapadula and Gori that careful planning is essential for studies that include discontinuation of treatment due to toxicity as an endpoint. For this reason, toxicity endpoints in our study were pre-defined and strictly categorized according to the DAIDS toxicity table. Tolerability was also strictly defined as the intent of the participant to discontinue the treatment due to toxicity. We believe that participant-driven tolerability discontinuations for toxicity are a necessary and useful measure when comparing commercially available medications. However, we agree with Dr. Lapadula that results from randomized studies can be further informed through study of observational cohorts. In a recent analysis, 11.7% of Korean patients discontinued atazanavir due to jaundice (1); compared to 7.8% of participants. This despite Koreans’ lower frequency of a polymorphism in UDP glucuronosyl transferase 1A1 associated with atazanavir-induced hyperbilirubinemia than is found in the HIV-1-infected population in the United States.(2,3) Our study population may therefore have facilitated our ability to detect this important tolerability difference between DHHS-recommended ritonavir-boosted protease inhibitors.

1. Choe PG, Park WB, Song K-Y, Bang J-H, Kim ES, Park S-W, et. al. Effect of Ritonavir-boosting on Atazanavir Discontinuation due to Jaundice in HIV-infected Koreans. Infect Chemother 2012, 44(3):175-179.
2. Park WB, Choe PG, Song K-H, Jeon JH, Bang J-H, Park SW, Kim HB, et. al. Genetic Factors Influencing Severe Atazanavir-Associated Hyperbilirubinemia in a Population with Low UDP-Glucuronosyltransferase 1A1*28 Allele Frequency. Clin Infect Dis 2010, 51(1):101–106.
3. Hall D1, Ybazeta G, Destro-Bisol G, Petzl-Erler ML, Di Rienzo A. Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 1999, 9(5):591-9.
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Summary for Patients

Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

The full report is titled “Efficacy and Tolerability of 3 Non-nucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1. A Randomized, Controlled Equivalence Trial.” It is in the 7 October 2014 issue of Annals of Internal Medicine (volume 161, pages 461-471). The authors are J.L. Lennox, R.J. Landovitz, H.J. Ribaudo, I. Ofotokun, L.H. Na, C. Godfrey, D.R. Kuritzkes, M. Sagar, T.T. Brown, S.E. Cohn, G.A. McComsey, F. Aweeka, C.J. Fichtenbaum, R.M. Presti, S.L. Koletar, D.W. Haas, K.B. Patterson, C.A. Benson, B.P. Baugh, R.Y. Leavitt, J.F. Rooney, D. Seekins, and J.S. Currier, for the ACTG A5257 Team.

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