Induction-maintenance Strategy Research Articles

Induction maintenance with tumour necrosis factor-inhibitor combination therapy with discontinuation versus methotrexate monotherapy in early rheumatoid arthritis: a systematic review and meta-analysis of efficacy in randomised controlled trials

ObjectiveTo determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with...

PMO-176 Induction maintenance treatment in chronic hepatitis B; step-down from tenofovir and lamivudine to lamivudine monotherapy is effective

IntroductionTenofovir Disoproxil Fumarate (TDF) is a potent and effective oral antiviral used to treat Chronic Hepatitis B (CHB), but concerns remain about possible long-term toxicity and the costs of indefinite...

Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study

AimTo assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy.MethodsA phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal...

Complete regression of HIV-associated multicentric Castleman disease treated with rituximab and thalidomide

Complete regression of HIV-associated multicentric Castleman disease treated with rituximab and thalidomide

Induction therapy with trizivir plus efavirenz or lopinavir/ritonavir followed by trizivir alone in naive HIV-1-infected adults

Induction-maintenance strategies were associated with a low response rate. We compared the virological response with two different induction regimens with trizivir plus efavirenz or lopinavir/ritonavir. A randomized, multicentre, open-label clinical trial with 209 antiretroviral-naive HIV-infected patients assigned to trizivir plus either efavirenz or lopinavir/ritonavir during 24-36 weeks. Patients reaching undetectable plasma viral loads during induction entered a 48-week maintenance on trizivir alone. The primary endpoint was the proportion of patients without treatment failure at 72 weeks using an intent to treat (ITT) analysis (switching equals failure). Patients were randomly assigned (efavirenz 104; lopinavir/ritonavir 105), and 114 (55%) entered the maintenance phase (efavirenz 54; lopinavir/ritonavir 60). Baseline characteristics were balanced between groups. The response rate at 72 weeks was 31 and 43% (ITT analysis, P = 0.076) and 63 and 75% (on-treatment analysis, P = 0.172) in the efavirenz and lopinavir/ritonavir arms, respectively. Virological failure occurred in 27 patients: six during induction (efavirenz, three; lopinavir/ritonavir, three; P = 1.0) and 21 during maintenance (efavirenz, 14; lopinavir/ritonavir, seven; P = 0.057). Thirty-four patients in the efavirenz arm switched treatment because of adverse events compared with 25 in the lopinavir/ritonavir arm (P = 0.17). Trizivir plus either efavirenz or lopinavir/ritonavir followed by maintenance with trizivir achieved a low but similar response at 72 weeks, with a high incidence of adverse events leading to drug discontinuation during the induction phase in both arms. The study showed a trend towards an increased virological failure rate in the efavirenz arm during the maintenance phase.

Abacavir sulfate/lamivudine/zidovudine fixed combination in the treatment of HIV infection

Treatment of HIV infection has typically been carried out using two nucleoside analogs and a protease inhibitor. Such regimens can be complex and have high pill burdens. Use of alternative regimens, such as triple nucleoside-based regimens, can improve adherence and decrease toxicities associated with protease inhibitor therapy. A formulation of abacavir sulfate/lamivudine/zidovudine allows a dosing schedule of one pill twice daily. The components have performed favorably compared with protease inhibitor-based regimens, such as indinavir. Compared with efavirenz-based regimens, abacavir sulfate/lamivudine/zidovudine has not performed as well. The combination is being studied as a cornerstone for induction maintenance strategies, in which switching a patient to abacavir sulfate/lamivudine/zidovudine has been associated with similar virologic outcomes as continuing with either protease inhibitor- or efavirenz-based regimens. Administration of abacavir sulfate/lamivudine/zidovudine also avoids side effects of antiretroviral therapy, such as hyperlipidemia, but its use is associated with a hypersensitivity reaction in a small number of patients. The combination of abacavir sulfate/lamivudine/zidovudine is an important part of the HIV armamentarium. Its potency and ease of administration make it worth consideration in the treatment of HIV, either by itself or in combination with other agents.

A Virological Benefit from an Induction/Maintenance Strategy: The Forte Trial

To evaluate whether the addition of a fourth drug for up to 32 weeks to a standard three-drug antiretroviral combination decreases the risk of virological failure without increasing toxicity in treatment-naive patients. Induction/maintenance (IM) therapy [two nucleoside reverse transcriptase inhibitors (NRTIs) + one non-NRTI (NNRTI) + one protease inhibitor for 24-32 weeks until plasma HIV RNA viral load (VL) < or =50 copies/ml then two NRTIs + NNRTI] was compared with standard therapy (ST) (two NRTIs + NNRTI). The primary endpoint was virological failure: VL >50 copies/ml at 32 (and 24) weeks or subsequent rebound to >400 copies/ml. 122 (62 IM, 60 ST) participants were randomized and followed for a median of 81 weeks (IQR 64-145). 52% were asymptomatic; median CD4+ T-cell count was 160 x 10(6)/l (IQR 92-260) and median VL 98,830 copies/ml (IQR 37,500-241,290). In an intent-to-treat analysis, the proportion of participants with virological failure at or after 32 weeks was higher in the ST arm [26 (43%) versus 11 (18%), P = 0.002]. The mean decrease in VL at 48 weeks was 0.84 95% confidence interval (CI) (0.15, 1.53) log10 copies/ml greater in the IM arm (P = 0.02). There were no significant differences between the two arms in the change in CD4+ T-cell count from baseline to 48 weeks, the number of participants with adverse events or the frequency of progression to AIDS/death. Drug resistance at failure was detected less frequently in the IM arm. Starting antiretroviral therapy with an IM strategy improved virological outcomes compared with a three-drug regimen, without significantly increasing toxicity.

Quadruple-Drug Induction HAART in Advanced HIV Infection

A randomized controlled study exploring an induction-maintenance strategy was performed with a quadruple-drug regimen: zidovudine/lamivudine/abacavir/nevirapine. The study was prematurely interrupted due to the high proportion of adverse events. The median time on protocol-defined therapy was 110 days; 13/28 (46%) patients interrupted therapy and 2/6 tested patients selected praecox viral mutants. Despite this, we observed a significant (p ≤ .001) increment of CD4. The theoretical advantages of induction-maintenance strategies are tempered by an increased risk of adverse experiences.