Second-line antiretroviral therapy:  long-term outcomes in South Africa.
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/mm(3) 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.
University of Southern California School of Medicine, Los Angeles, CA, USA.
Richard A
RA
Murphy
Department of Medicine, McCord Hospital, Durban, South Africa.
Henry
H
Sunpath
University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Carmen
C
Castilla
Department of Medicine, McCord Hospital, Durban, South Africa.
Shameez
S
Ebrahim
University of Cape Town, Cape Town, South Africa.
Richard
R
Court
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Hoang
H
Nguyen
Section of Retroviral Therapeutics, Brigham and Women's Hospital, Boston, MA, USA.
Daniel
D
Kuritzkes
Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
Vincent C
VC
Marconi
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Jean B
JB
Nachega
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D013019:South Africa; D016896:Treatment Outcome; D019562:Viral Load; D016903:Drug Monitoring
D019380:Anti-HIV Agents