DESIGN                      A5273 is a phase III, dual-arm, open-label, randomized, non-inferiority study for participants who are on a failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing first-line regimen. The study will evaluate the difference in virologic failure rate between two treatment arms: lopinavir/ritonavir plus raltegravir (LPV/r + RAL) and LPV/r plus best available nucleos(t)ide reverse transcriptase inhibitors (NRTIs).The NRTIs to be used will be specified by the site prior to randomization.

NOTE: On-study virologic failure is defined as confirmed viral load >400 copies/mL at or after week 24.

DURATION                Each participant will be followed for 96 weeks after enrollment.

SAMPLE SIZE            600 (300 per study arm)

POPULATION            Human immunodeficiency virus (HIV)-1 infected adults (age ≥18 years) who have confirmed virologic failure on an NNRTI-containing first-line regimen.

STRATIFICATION     Participants will be stratified by screening HIV-1 RNA (≥100,000 versus <100,000 copies/mL), screening CD4+ cell count (≥100 versus <100 cells/mm³), and selection of ZDV in the NRTI regimen (yes/no). Randomization will be balanced by site.

REGIMEN: At entry, all participants will stop the failing NNRTI-based regimen and switch to one of the following arms, randomly assigned in a 1:1 ratio:

Arm A: LPV/r plus RAL

Arm B: LPV/r plus best available NRTIs

Best available NRTI combinations will be selected by the site investigator prior to randomization from a list of combinations approved by the study or in consultation with the A5273 Clinical Management Committee (CMC). The NRTIs provided by the study are emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), abacavir/lamivudine/zidovudine (ABC/3TC/ZDV), abacavir/lamivudine (ABC/3TC), lamivudine/zidovudine (3TC/ZDV), abacavir (ABC), lamivudine (3TC), and zidovudine (ZDV).