Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial.
BACKGROUND
Daily oral triple therapy is effective at halting HIV disease progression, but can have toxic effects and is costly. We investigated whether dual therapy with lopinavir and ritonavir plus lamivudine is non-inferior to standard triple therapy.


METHODS
The GARDEL study (Global AntiRetroviral Design Encompassing Lopinavir/r and Lamivudine vs LPV/r based standard therapy) is a 48 week, phase 3, randomised, controlled, open-label, non-inferiority trial in antiretroviral-therapy-naive adults (age ≥18 years) with documented HIV-1 RNA viral load of at least 1000 copies per mL. The study was done at 19 centres in six countries. Patients were randomly assigned (1:1) to dual therapy or triple therapy by sealed envelopes, in blocks of four, stratified by baseline viral load (<100,000 vs ≥100,000 copies per mL). Dual therapy consisted of lopinavir 400 mg and ritonavir 100 mg plus lamivudine 150 mg, both twice daily. Triple therapy consisted of lopinavir 400 mg and ritonavir 100 mg twice daily and lamivudine or emtricitabine plus another nucleoside reverse transcriptase inhibitor (NRTI) in fixed-dose combination. Efficacy was analysed in all participants who received at least one dose of study drug. The primary endpoint was virological response rate, defined as the proportion of patients with HIV RNA less than 50 copies per mL at 48 weeks. Dual therapy was classed as non-inferior to triple therapy if the lower bound of the 95% CI for the difference between groups was no lower than -12%. Patients and investigators were unmasked to treatment allocation. This study is registered with ClinicalTrials.gov, number NCT01237444.


RESULTS
Between Dec 10, 2010, and May 15, 2012, 217 patients were randomly assigned to the dual-therapy group and 209 to the triple-therapy group. 198 patients in the dual-therapy group and 175 in the triple-therapy group completed 48 weeks of treatment. At week 48, 189 patients (88·3%) in the dual-therapy group and 169 (83·7%) in the triple-therapy group had viral response (difference 4·6%, 95% CI -2·2 to 11·8; p=0·171). Patients with baseline viral load of at least 100,000 copies per mL showed similar results (87·2% vs 77·9%, respectively; difference 9·3%, 95% CI -2·8 to 21·5; p=0·145). Toxicity-related or tolerability-related discontinuations were more common in the triple-therapy group (n=10 [4·9%]) than in the dual-therapy group (n=1 [0·4%]; difference 4·5%, 95% CI -8·1 to -0·9; p=0·011). 65 adverse events in the dual-therapy group and 88 in the triple-therapy group were possibly or probably drug related (p=0·007). Two serious adverse events occurred, both in the dual-therapy arm, one of which (a case of gastritis) was reported as possibly or probably related to drug treatment.


CONCLUSIONS
Dual therapy with lopinavir and ritonavir plus lamivudine regimen warrants further clinical research and consideration as a potential therapeutic option for antiretroviral-therapy-naive patients.


BACKGROUND
Fundación Huésped and AbbVie.
Clinical Research Department, Fundación Huésped, Buenos Aires, Argentina. Electronic address: pedro.cahn@huesped.org.ar.
Pedro
P
Cahn
HIV Unit, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Mexico.
Jaime
J
Andrade-Villanueva
Internal Medicine, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
José R
JR
Arribas
Infectious Unit, Hospital Clínic/IDIBAPS, University of Barcelona, Barcelona, Spain.
José M
JM
Gatell
Asociación Civil Impacta Salud y Educación, Lima, Peru.
Javier R
JR
Lama
Medical Affairs Therapeutic Area, Virology and Nanotechnology, Global Pharmaceutical Research and Development, AbbVie, Chicago, IL, USA.
Michael
M
Norton
Clinical Research Department, Fundación Huésped, Buenos Aires, Argentina.
Patricia
P
Patterson
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Juan
J
Sierra Madero
Clinical Research Department, Fundación Huésped, Buenos Aires, Argentina.
Omar
O
Sued
Clinical Research Department, Fundación Huésped, Buenos Aires, Argentina.
Maria Inés
MI
Figueroa
Clinical Research Department, Fundación Huésped, Buenos Aires, Argentina.
Maria José
MJ
Rolon
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D055815:Young Adult
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D019438:Ritonavir