Antiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens.

TitleAntiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens.
Publication TypeJournal Article
Year of Publication2014
AuthorsZheng Y, Hughes MD, Lockman S, Benson CA, Hosseinipour MC, Campbell TB, Gulick RM, Daar ES, Sax PE, Riddler SA, Haubrich R, Salata RA, Currier JS
JournalClin Infect Dis
Volume59
Issue6
Pagination888-96
Date Published2014 Sep 15
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Randomized Controlled Trials as Topic, Retreatment, Reverse Transcriptase Inhibitors, Treatment Outcome, Viral Load
Abstract

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.

DOI10.1093/cid/ciu367
Alternate JournalClin. Infect. Dis.
PubMed ID24842909
PubMed Central IDPMC4155445
Grant List1 UM1 AI068634 / AI / NIAID NIH HHS / United States
1 UM1 AI068636 / AI / NIAID NIH HHS / United States
A1069424 / / PHS HHS / United States
AI064086 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
UL1 RR024996 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UL1RR024996 / RR / NCRR NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069419 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069456 / AI / NIAID NIH HHS / United States
UM1 AI069472 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1AI069412 / AI / NIAID NIH HHS / United States
UM1AI069419 / AI / NIAID NIH HHS / United States
UM1AI069472 / AI / NIAID NIH HHS / United States