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Second-Line Antiretroviral Therapy: Long-Term Outcomes in South Africa

Murphy, Richard A. MD, MPH*; Sunpath, Henry MBBS, MPH; Castilla, Carmen MD; Ebrahim, Shameez BPharm; Court, Richard MBChB§; Nguyen, Hoang MD, MPH; Kuritzkes, Daniel R. MD; Marconi, Vincent C. MD#; Nachega, Jean B. MD, MPH, PhD**

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1st, 2012 - Volume 61 - Issue 2 - p 158–163
doi: 10.1097/QAI.0b013e3182615ad1
Clinical Science

Background: Currently, boosted protease inhibitor–containing regimens are the only option after first-line regimen failure available for patients in most resource-limited settings, yet little is known about long-term adherence and outcomes.

Methods: We enrolled patients with virologic failure (VF) who initiated lopinavir/ritonavir–containing second-line antiretroviral therapy (ART). Medication possession ratios were calculated using pharmacy refill dates. Factors associated with 12-month second-line virologic suppression [viral load (VL) <50 copies/mL] and adherence were determined.

Results: One hundred six patients (median CD4 count and VL at failure: 153 cells/mm3 and 28,548 copies/mL, respectively) were enrolled. Adherence improved after second-line ART switch (median adherence 6 months prior, 67%; median adherence during initial 6 months of second-line ART, 100%; P = 0.001). Higher levels of adherence during second-line ART was associated with virologic suppression at month 12 of ART (odds ratio 2.5 per 10% adherence increase, 95% CI 1.3 to 4.8, P = 0.01). Time to virologic suppression was most rapid among patients with 91%–100% adherence compared with patients with 80%–90% and <80% adherence (log rank test, P = 0.01). VF during 24 months of second-line ART was moderate (month 12: 25%, n = 32/126; month 18: 21%, n = 23/112; and month 24: 25%, n = 25/99).

Conclusions: The switch to second-line ART in South Africa was associated with an improvement in adherence, however, a moderate ongoing rate of VF—among approximately 25% of patients receiving second-line ART patients at each follow-up interval—was a cause for concern. Adherence level was associated with second-line ART virologic outcome, helping explain why some patients achieved virologic suppression after switch and others did not.

*Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY

Department of Medicine, McCord Hospital, Durban, South Africa

Department of Medicine, Brigham and Women's Hospital, Boston, MA

§Department of Medicine, University of Cape Town, Cape Town, South Africa

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

#Department of Medicine, Infectious Disease Division, Emory University School of Medicine, Atlanta, GA

**Department of Medicine, Centre for Infectious Diseases, Stellenbosch University, Cape Town, South Africa

Correspondence to: Richard A. Murphy, Richard A. Murphy, MD, MPH, 1621 Eastchester Road, Bronx, NY 10461 (e-mail:

Supported in part by the IDSA Medical Scholars Program, the Arnold P. Gold Foundation Medical Student Scholarship, Partners AIDS Research Center, McCord Hospital, and National Institutes of Health Grants K24-RR016482 and P30 AI060354.

Presented at the Conference on Retroviruses and Opportunistic Infections, February 2011, Boston, MA.

R. A. Murphy and H. Sunpath contributed equally to this work.

D. R. Kuritzkes is a consultant to, or has received research funding from Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck and Roche.

The other authors have no conflicts of interest to disclose.

Received February 17, 2012

Accepted May 24, 2012

© 2012 by Lippincott Williams & Wilkins