Comparison of PI vs. PI: ATV vs. ATV/r, LPV/r mono vs. LPV/r + ZDV/3TC
Examination of protease inhibitor regimens, including atazanavir and lopinavir/ritonavir, in mono or combination therapies, along with baseline characteristics, patient response at week 48, virologic failure rates, and resistance data.
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Comparison of PI vs PI ATV vs ATV/r LPV/r mono vs LPV/r + ZDV/3TC LPV/r QD vs BID BMS 089 MONARK M02-418 M05-730 A5073 GARDEL ALERT ATADAR KLEAN GEMINI CASTLE ARTEMIS LPV/r + 3TC vs LPV/r + 2 NRTI ATV/r vs FPV/r ATV/r vs DRV/r FPV/r vs LPV/r SQV/r vs LPV/r ATV/r vs LPV/r DRV/r vs LPV/r
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI Design Randomisation* 1 : 1 Open-label W48 W96 N = 217 > 18 years ARV-na ve LPV/r 400/100 mg + 3TC 150 mg BID HIV RNA > 1,000 c/mL Any CD4 cell count HBsAg negative No R to study drugs N = 209 LPV/r 400/100 mg BID + FDC of 2 NRTI** *Randomisation was stratified by HIV RNA (<or > 100,000 c/mL) at screening ** Investigator-selected NRTI : ZDV/3TC = 54%, TDF/FTC = 37%, ABC/3TC = 9% Objective Non inferiority of LPV/r + 3TC at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower limit of the 95% CI for the difference = -12%, 85% power) Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI Baseline characteristics and patient disposition LPV/r + 3TC N = 214 34 16% 4.87 44% 319 21% 16 (7.5%) N = 1 N = 1 N = 7 N = 5 N = 1 0 N = 1 LPV/r + 2 NRTI N = 202 35 17% 4.87 43% 329 19% 27 (13.4%) N = 6 N = 10 N = 9 N = 1 0 N = 1 0 Median age, years Female HIV RNA (log10 c/mL), median HIV RNA > 100,000 c/mL CD4 cell count (/mm3), median CD4 < 200 per mm3 Discontinuation by W48 For virologic failure at week 24 For adverse event Lost to follow-up Non-compliance Death Opportunistic infection Pregnancy Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI Response to treatment at week 48 HIV RNA < 50 c/mL All patients Primary analysis All patients Baseline HIV-1 RNA 100 000 c/mL % 96.6 100 95.5 LPV/r + 3TC LPV/r + 2 NRTI 88.3 87.2 83.7 77.9 75 50 Median CD4/mm3 increase : + 227 (LPV/r + 3TC) vs + 217 (LPV/r + 2 NRTI) 25 0 ITT, snapshot ITT, snapshot Observed Adjusted difference (95% CI)= 4.6% (- 2.2 ; 11.8) Adjusted difference (95% CI)= 9.3%(- 2.8 ; 21.5) Adjusted difference (95% CI)= - 1.1% (- 5.6 ; 3.4) Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI Virologic failure definition - 2 consecutive HIV-1 RNA > 400 c/mL at or after W24 - HIV-1 RNA > 50 c/mL at W48 Resistance data at week 48 LPV/r + 3TC LPV/r + 2 NRTI Virologic failure 10 12 At week 24 1 6 At week 48 9 6 Median HIV-1 RNA at virologic failure, c/mL 236 1027 Success of amplification for genotype testing 5/10 7/12 Presence of resistance mutations 2 0 M184V Protease inhibitor resistance 2 0 - - Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI Adverse events LPV/r + 3TC LPV/r + 2NRTI P Grade 2-3 AE possibly or probably drug related 65 (30%) 88 (44%) 0.007 Patients with grade 2-3 AE possibly or probably drug related 43 48 - Drug-related AE 2% in either group Hyperlipidaemia 23 16 - Diarrhoea 14 14 - Nausea 2 9 0.05 Dyspepsia 2 6 0.02 AE leading to discontinuation 2 (1%) 11 (5%)* 0.01 NRTI related - Zidovudine 0 11 10 (anaemia = 3, GI, N = 6, rash = 1) 1 (rash) - Tenofovir Selected grade 3-4 laboratory abnormalities occurred at the same frequency in both groups, except for hyperlipidemia (more frequent in dual therapy group) Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI Summary LPV/r + 3TC dual therapy was virologically non inferior to a standard therapy of LPV/r + 2 NRTI Similar virologic response of the 2 regimens in patients with HIV RNA > 100 000 c/mL at enrolment No resistance mutations to protease inhibitor at virologic failure in either group 2 patients with M184V in dual therapy group Incidence of adverse events higher in triple therapy group Discontinuation because of adverse events mainly related to NRTI in the LPV/r + NRTI arm Potential advantages of first-line LPV/r + 3TC Cost Less toxicity (might need less monitoring) Spares the other NRTIs Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL
