Raltegravir Plus Nucleoside Reverse-Transcriptase Inhibitor (NRTI) Plus Lopinavir, NRTIs Plus Lopinavir for Second-Line Treatment of HIV: 96-Week Follow-up Results from a Randomized Controlled Trial

Abstract

Background: A boosted protease inhibitor (PI) plus two nucleoside reverse-transcriptase inhibitors (NRTIs) or a boosted PI plus an integrase inhibitor is recommended as second-line antiretroviral therapy (ART) alternatives. Our study aimed to evaluate the efficacy and safety of raltegravir (RAL)-based and lopinavir-boosted ritonavir (LPV/r)-based regimens as second-line options in the Chinese population. Methods: A multicenter, open-label, prospective, randomized controlled cohort study was performed at 18 research sites in China. Human immunodeficiency virus (HIV)-infected adults with a plasma viral load >400 copies/mL after at least 1 year of first-line ART were enrolled. Participants were randomized in a 2:1 ratio to receive oral RAL plus tenofovir disoproxil fumarate (TDF) plus LPV/r (RAL group) and lamivudine (3TC) plus TDF plus LPV/r (LPV/r group) for 48 weeks. The primary endpoint was a plasma viral load <400 copies/mL at the 48th week, which was measured by reverse transcription polymerase chain reaction (RT-PCR). Other important indicators, such as cluster of differentiation 4 (CD4) cell count and HIV-1 DNA, were measured by flow cytometry and quantitative PCR, respectively. Results: A total of 175 patients were randomized to either the RAL group (n = 119) or the LPV/r group (n = 56). High levels of drug resistance to both TDF and 3TC were observed in both groups (41.4% vs. 39.5%, p = 0.84). At the 48th week, the viral load <400 copies/mL was achieved in 100 (94.3%) out of 106 patients in the RAL group and 47 (92.2%) out of 59 patients in the LPV/r group (p = 0.60). There was non-significant difference between the two groups in the percentage of patients with cluster of CD4 cell counts >200 cells/μL (85.0% vs. 76.5%, p = 0.19). Likewise, the non-significant decrease in HIV-1 DNA was observed in the two groups at the 48th week. Faster viral suppression and CD4 cell recovery were observed in the RAL group. Conclusions: The LPV/r-based regimen as a second-line ART demonstrated a similar effective long-term virologic suppression rate compared to the RAL-based regimen. A regimen of NRTIs plus PI remains the most effective and cost-effective second-line option in developing regions. Clinical Trial Registration: NCT01844310; Registered May 1, 2013. Available at: https://clinicaltrials.gov/study/NCT01844310.