RESUMO
BACKGROUND: In virologically suppressed patients, switching to darunavir/ritonavir monotherapy could avoid resistance and adverse events from continuing nucleoside analogues. METHODS: Two hundred and fifty-six patients with HIV RNA <50 copies/mL on current antiretrovirals were switched to darunavir/ritonavir 800/100 mg once daily, either as monotherapy (n = 127) or with two nucleoside analogues (n = 129). Treatment failure was defined as two consecutive HIV RNA levels at least 50 copies/mL by week 96, or discontinuation of study drugs. The trial had 80% power to show non-inferiority (δ = -12%) at week 48. Results Patients were 81% male, 91% Caucasian, and had a median baseline CD4 count of 575 cells/mm(3). There were more patients with hepatitis C co-infection at baseline in the monotherapy arm (18%) compared with the triple therapy arm (12%). In the efficacy analysis, HIV RNA <50 copies/mL by week 96 (per protocol, time to loss of virological response, switch equals failure) was 78% versus 82% in the monotherapy and triple therapy arms [difference -4.2%, 95% confidence interval (CI) -14.3% to +5.8%]; in a switch included analysis, HIV RNA <50 copies/mL was 93% versus 92% (difference +1.6%, 95% CI -5.0% to +8.1%). The percentage of patients with HIV RNA <5 copies/mL (optical density from the sample equal to the negative control) remained constant over time in both treatment arms. Conclusions In the week 96 analysis of the MONotherapy in Europe with TMC114 (MONET) trial, switching to darunavir/ritonavir monotherapy showed non-inferior efficacy to darunavir/ritonavir plus two nucleoside analogues in the switch included and observed failure analyses, but not in the main switch equals failure analysis.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Nucleosídeos/administração & dosagem , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Darunavir , Europa (Continente) , Feminino , Humanos , Masculino , RNA Viral/sangue , Falha de TratamentoRESUMO
The potential of advanced polymer or hybrid polymer membranes to reduce CO2 emissions in steel production was evaluated. For this, a conceptual process design and assessment was performed for a process that is a combination of carbon recycling and electrification of the steel making process. The results indicate a CO2 avoidance of 9%. CO2 emissions were reduced by factor 1.78 when using renewable electricity according to the proposed scheme compared to feeding this renewable electricity to the electrical grid. The CO2 abatement potential of the studied concept is highly dependent on the CO2 conversion in the plasma torch. If CO2 conversion in the plasma torch could be increased from 84.4% to 95.0%, the overall CO2 avoidance could be further increased to 16.5%, which is comparable to the values reported for the top gas recycling blast furnace. In this case, the CO2 emissions reduction achieved when using renewable electricity in the proposed scheme compared to using the same electricity in the electrical grid increases a factor from 1.78 to 3.27.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Proteína gp41 do Envelope de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Piridazinas/uso terapêutico , RNA Viral/sangue , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Enfuvirtida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Projetos Piloto , Pirimidinas , Resultado do TratamentoRESUMO
BACKGROUND: The Study of Etravirine Neuropsychiatric Symptoms versus Efavirenz (SENSE) trial compared etravirine with efavirenz in treatment-naive patients. The primary endpoint was neuropsychiatric adverse events up to week 12; HIV RNA suppression at week 48 was a secondary endpoint. METHODS: Patients with HIV RNA more than 5000â copies/ml were randomized to etravirine 400 âmg once daily (nâ=â79) or efavirenz (nâ=â78), plus two nucleoside analogues. HIV RNA less than 50 âcopies/ml at week 48 was analysed using the time to loss of virological response (TLOVR) algorithm. Drug resistance at treatment failure and safety endpoints were also evaluated. RESULTS: At baseline, the median CD4 cell count was 302 âcells/µl and HIV RNA was 4.8âlog10â copies/ml. In the intent to treat TLOVR analysis at week 48, 60 of 79 (76%) patients on etravirine versus 58 of 78 (74%) on efavirenz had HIV RNA less than 50 âcopies/ml. In the on-treatment analysis, 60 of 65 (92%) taking etravirine had HIV RNA les than 50âcopies/ml versus 58 of 65 (89%) for efavirenz: etravirine showed noninferior efficacy versus efavirenz in both analyses (Pâ<â0.05). Four patients had virological failure in the etravirine arm: none developed resistance to nucleoside analogues or nonnucleosides. Seven patients had virological failure in the efavirenz arm: three developed treatment-emergent resistance to nucleoside analogues and/or nonnucleosides. At the week 48 visit, the percentage with ongoing neuropsychiatric adverse events was 6.3% for etravirine and 21.5% for efavirenz (Pâ=â0.011). CONCLUSION: First-line treatment with etravirine 400âmg once daily and two nucleoside reverse transcriptase inhibitors (NRTIs) led to similar rates of HIV RNA suppression, compared with efavirenz and two NRTIs. None of the patients with virological failure in the etravirine arm developed resistance to nonnucleosides.