Antiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens.
BACKGROUND
Virologic failure (VF) on a first-line ritonavir-boosted protease inhibitor (PI/r) regimen is associated with low rates of resistance, but optimal management after failure is unknown.


METHODS
The analysis included participants in randomized trials who experienced VF on a first-line regimen of PI/r plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) and had at least 24 weeks of follow-up after VF. Antiretroviral management and virologic suppression (human immunodeficiency virus type 1 [HIV-1] RNA <400 copies/mL) after VF were assessed.


RESULTS
Of 209 participants, only 1 participant had major PI-associated treatment-emergent mutations at first-line VF. The most common treatment approach after VF (66%) was to continue the same regimen. The virologic suppression rate 24 weeks after VF was 64% for these participants, compared with 72% for those who changed regimens (P = .19). Participants remaining on the same regimen had lower NRTI resistance rates (11% vs 30%; P = .003) and higher CD4(+) cell counts (median, 275 vs 213 cells/µL; P = .005) at VF than those who changed. Among participants remaining on their first-line regimen, factors at or before VF significantly associated with subsequent virologic suppression were achieving HIV-1 RNA <400 copies/mL before VF (odds ratio [OR], 3.39 [95% confidence interval {CI}, 1.32-8.73]) and lower HIV-1 RNA at VF (OR for <10 000 vs ≥10 000 copies/mL, 3.35 [95% CI, 1.40-8.01]). Better adherence after VF was also associated with subsequent suppression (OR for <100% vs 100%, 0.38 [95% CI, .15-.97]). For participants who changed regimens, achieving HIV-1 RNA <400 copies/mL before VF also predicted subsequent suppression.


CONCLUSIONS
For participants failing first-line PI/r with no or limited drug resistance, remaining on the same regimen is a reasonable approach. Improving adherence is important to subsequent treatment success.
Harvard School of Public Health.
Yu
Y
Zheng
Harvard School of Public Health.
Michael D
MD
Hughes
Harvard School of Public Health Harvard Medical School, Boston, Massachusetts.
Shahin
S
Lockman
University of California, San Diego.
Constance A
CA
Benson
University of North Carolina, Chapel Hill.
Mina C
MC
Hosseinipour
University of Colorado Denver, Aurora.
Thomas B
TB
Campbell
Weill Medical College, Cornell University, Ithaca, New York.
Roy M
RM
Gulick
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
Eric S
ES
Daar
Harvard Medical School, Boston, Massachusetts.
Paul E
PE
Sax
University of Pittsburgh, Pennsylvania.
Sharon A
SA
Riddler
University of California, San Diego.
Richard
R
Haubrich
Case Western Reserve University, Cleveland, Ohio.
Robert A
RA
Salata
University of California, Los Angeles.
Judith S
JS
Currier
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors
antiretroviral therapy; first-line; protease inhibitor; virologic failure