RESUMEN
Background/Aims: Switching from a three-drug regimen (3DR: boosted darunavir [bDRV] and two nucleoside reverse transcriptase inhibitors [NRTIs]) to a two-drug regimen (2DR: bDRV and dolutegravir [DTG]) demonstrated non-inferiority with regard to viral suppression in people living with HIV (PLWH) in the DUALIS study. This sub-analysis focuses on changes in metabolic and renal parameters when sparing the NRTI backbone.Methods: DUALIS was a randomized, open-label, multicenter (27) phase 3-trial. Participants were virologically suppressed (HIV-RNA < 50 copies/mL) on 3DR for at least 24 weeks. Subjects were either switched to DTG 50 mg + bDRV 800 mg (with ritonavir 100 mg) (2DR) or continued their regimen consisting of two NRTIs in combination with ritonavir-bDRV (3DR) once daily. Data of metabolic and renal parameters at baseline and week 48 were compared.Results: The LDL-fraction increased by + 13.3 (-3.0 to +31.3) mg/dL on 2DRs and was stable (-14.0 to +18.0 mg/dL) on 3DRs (p < 0.0010).PLWH gained +2.0 (-0.2 to +4.0) kg and +0.2 (-1.9 to +2.1) kg in body weight on 2DRs and 3DRs, respectively 3 (p = 0.0006).The MDRD eGFR decreased by -7,8 (-17.4 to -0.3) mL/min/1.73m2 and 0.4 (-8.8 to +5.7) mL/min/1.73m2 on 2DRs and 3DRs, respectively (p = 0.0002), while serum levels of cystatin C were stable in both arms (2DR: -0.1 to +0.1 mg/L; 3DR: 0.0 to +0.1 mg/L).Conclusions: While being non-inferior in terms of viral suppression, sparing the NRTI backbone showed a non-favorable profile in metabolic or renal parameters over 48 weeks.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Fármacos Anti-VIH/uso terapéutico , Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Ritonavir/uso terapéuticoRESUMEN
BACKGROUND: NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. METHODS: Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. RESULTS: After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. CONCLUSIONS: The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.
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Antígenos CD57/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Linfocitos T/metabolismo , Adulto , Quimioterapia Combinada , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Total HIV-DNA load in peripheral blood cell (PBMCs) reflects the global viral reservoir that seems not to be affected by antiretroviral treatment. However, some studies reported a different permeability of different drugs in cellular compartments. OBJECTIVE: To investigate the relation between the amount of total HIV-1 DNA and different treatment strategies. METHODS: Total HIV-1 DNA was quantified by real time PCR in PBMCs collected from 161 patients with long-term undetectable HIV-RNA receiving different therapy schedules (3-drug regimens or 2-drug regimen containing Raltegravir as integrase inhibitor). RESULTS: Overall, HIV patients who started therapy with a median pre-ART CD4+ cell count >400 cells/mm3 and HIV viral load of 3 log10 copies/ml, achieved a lower amount of HIV total DNA. No significant correlation was found in DNA size when patients were stratified on the basis of different therapeutic protocols. However, HIV DNA load analysis, when only performed in HIV patients with a median pre-ART CD4+ cell count >200 cells/mm3 and HIV viral load < 3 log10 copies/ml, showed a significative DNA decrease in Raltegravir treated group with respect to the NNRTIs-treated group. CONCLUSION: The data emphasize that HIV-DNA level represents a predictive factor in long-term suppressive therapy patients. In addition, the diminished reservoir, only observed in patients treated with the NRTI-sparing regimen RAL plus PI/r before immunological and virological derangement, suggests that latest generation drugs, such as integrase inhibitors, might represent an optimal chance in the management of HIV infection.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Provirus/genética , Carga Viral , Adulto , Fármacos Anti-VIH/farmacología , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , ADN Viral , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral , Resultado del TratamientoRESUMEN
BACKGROUND: The advent of well-tolerated and effective anti-retroviral drugs against human immunodeficiency virus-1 (HIV-1) infection has been a major step forward that has achieved long-term survival in recent years. The number of HIV-1 infected patients who experience difficulty in swallowing tablets is expected to increase as the HIV-infected population advances in age or develops comorbidities or treatment sequelae affecting the central nervous system. CASE PRESENTATION: Here, we describe two HIV-1-infected patients who experienced progressive dysphagia leading to inability to swallow the antiretroviral tablets included in the standard regimen. Both patients had a plasma viral load < 40 copies/mL while receiving anti-retroviral therapy with the recommended combination antiretroviral therapy (cART) regimen, but the dysphagia necessitated a switch. By switching to much smaller sized combined regimen of dolutegravir (DTG) plus rilpivirine (RPV) tablets, both of our patients were able to successfully continue treatment and maintain adherence without the need for crushing tablets or preparing an oral suspension. Additionally, switching from the recommended cART regimen to DTG plus RPV successfully maintained viral suppression. At the last available follow-up (12 months after switching to DTG/RPV), HIV-1 viral load remained below the lower limit of quantification. CONCLUSIONS: An alternative therapeutic option that takes tablet size into consideration could not only contribute to improved patient adherence, but also a reduced care burden for HIV-infected patients with dysphagia. Thus, switching to the "small-tablet regimen" of DTG plus RPV has the potential to improve the survival and well-being of patients with dysphagia.
RESUMEN
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. OBJECTIVES: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. STUDY DESIGN: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan-Meier curves and Cox regression models were performed to estimate time to event probability. RESULTS: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9-31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1-13%] by 12 and 9% (95% CI 2-16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1-17%) and 22% (95% CI 11-33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01-0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25-0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6-779; p = 0.004). CONCLUSIONS: DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.
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Fármacos Anti-VIH/uso terapéutico , Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Raltegravir Potásico/uso terapéutico , Ritonavir/uso terapéutico , Carga Viral , Adulto , Fármacos Anti-VIH/efectos adversos , Estudios de Cohortes , Darunavir/efectos adversos , Quimioterapia Combinada/efectos adversos , Femenino , VIH-1/genética , Humanos , Italia , Masculino , Persona de Mediana Edad , ARN Viral/genética , Raltegravir Potásico/efectos adversos , Ritonavir/efectos adversosRESUMEN
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed. OBJECTIVE: To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics. METHODS: Fifty participants naïve to ART underwent HIV viral kinetic sampling evaluated using biexponential mixed effects modeling. A subset of 28 subjects (with complete viral suppression) underwent flow cytometry and evaluation of soluble markers of inflammation at weeks 0, 4, and 48 of ART. RESULTS: RAL + LPV/r compared to EFV/TDF/FTC resulted in a prolonged first phase viral decay rate (18 vs. 13 days p < 0.01). From weeks 0 to 4, RAL + LPV/r was associated with a trend toward greater decreases in activated CD4+ T cells (-3.81 vs. -1.18 p = 0.09) and less decreases in activated effector memory CD4+ T cells (-0.63 vs. -2.69 p-0.07). These trends did not persist to week 48. No differences were noted at any time point for soluble markers of immune activation. CONCLUSIONS: The prolonged first phase viral decay observed with RAL + LPV/r in persons starting ART did not result in differences in viral suppression at week 48. We also observed trends in declines in certain cellular markers of immune activation but it remains unclear if this could translate to long-term immunologic benefits in persons on an INSTI + PI.
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Infecciones por VIH/inmunología , Infecciones por VIH/virología , Linfocitos T/inmunología , Carga Viral , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Biomarcadores , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Memoria Inmunológica , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: Unboosted atazanavir with raltegravir has been investigated at 300mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations. OBJECTIVES: Atazanavir 200mg twice daily could increase tolerability and plasma exposure. STUDY DESIGN: Patients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated. RESULTS: 102 patients [72.5% male, age 46.4 years (42-54), BMI 24kg/m2 (22-26)] were included. CD4+ T lymphocytes were 417 cell/µL (302-704) and 76 patients (74.5%) had HIV-RNA <50 copies/ml. After 123 weeks 18.6% patients showed virological failure and 3.9% discontinued for intolerance. Available genotypes showed selection of major integrase (7/10 patients) and protease resistance-associated mutations (5/13 patients). In patients switching with dyslipidemia (n=67) total, LDL cholesterol and triglycerides significantly decreased. Patients switching with eCRCL<60ml/min (n=27) had no significant changes while patients with eCRCL >60ml/min showed significant decrease (-9.8ml/min, p=0.003) at 96-weeks. Atazanavir and raltegravir trough concentrations were 321ng/mL (147-720) and 412ng/mL (225-695). Self-reported non-adherence (n=4) was significantly associated with virological failure (p=0.02); patients with virological success had borderline longer previous virological control (33 vs. 18 months, p=0.07). DISCUSSION: Switch to atazanavir/raltegravir was safe and well tolerated allowing optimal drugs' plasma exposure. However, a concerning rate (18.6%) failed with newly selected mutations and stopped ATV/RAL because of DDI and intolerance issues or were lost to follow-up. This regimen might be considered in selected patients, without history of protease inhibitors failure or HBV infection, showing optimal adherence and prolonged suppression.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Sulfato de Atazanavir/administración & dosificación , Sulfato de Atazanavir/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Raltegravir Potásico/administración & dosificación , Raltegravir Potásico/efectos adversos , Adulto , Fármacos Anti-VIH/farmacocinética , Sulfato de Atazanavir/farmacocinética , Recuento de Linfocito CD4 , Farmacorresistencia Viral , Femenino , Infecciones por VIH/virología , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Plasma/química , Raltegravir Potásico/farmacocinética , Estudios Retrospectivos , Selección Genética , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Data on the efficacy of simplifying therapy using darunavir/ritonavir and lopinavir/ritonavir monotherapy in clinical practice remain limited. METHODS: A retrospective single-centre study including patients initiating darunavir/ritonavir or lopinavir/ritonavir monotherapy with a plasma HIV-1 viral load (pVL) <50 copies/mL and at least one subsequent follow-up visit. The primary endpoint was the percentage of patients remaining free of virological failure (VF; defined as a confirmed pVL >50 copies/mL or as any change in the regimen after a single determination with a pVL >50 copies/mL) during the follow-up. We also evaluated the percentage of patients remaining free of treatment failure (TF; defined as VF or the early discontinuation of monotherapy for any reason) and compared the effectiveness of the two regimens. Effectiveness was evaluated using cumulative survival analysis (at Weeks 48 and 96). Factors associated with VF and TF were analysed using Cox regression. RESULTS: A total of 522 patients were included (309 receiving lopinavir/ritonavir and 213 receiving darunavir/ritonavir). The median follow-up was 64.3 (30.5-143.0) weeks. The percentage of patients free of VF and TF was 94% (95% CI 91%-96%) and 79% (95% CI 75%-82%) at 48 weeks, respectively, and 86% (95% CI 81%-89%) and 62% (95% CI 57%-67%) at 96 weeks, respectively. The risk of VF was similar for the two regimens (HR=1.0, 95% CI 0.6-1.8; P=0.962). Lopinavir/ritonavir monotherapy was associated with a 1.5-fold greater risk of TF (95% CI 1.1-2.1; P=0.012) and a 2.3-fold greater risk of discontinuation of therapy due to adverse events (95% CI 1.3-3.9; P=0.003). CONCLUSIONS: The virological efficacy of darunavir/ritonavir and lopinavir/ritonavir monotherapy is high in clinical practice. Treatment discontinuation due to safety issues is more frequent with lopinavir/ritonavir.
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Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Adulto , Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Darunavir , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , VIH-1/aislamiento & purificación , Humanos , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Masculino , Estudios Retrospectivos , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento , Carga ViralRESUMEN
Novel combination antiretroviral regimens may be needed for selected HIV-infected patients with toxicity or resistance. We evaluated prospectively 25 virologically suppressed patients, largely pretreated (15.6 years on therapy) with antiretroviral drug toxicity (n=19) or interactions (n=9, mainly with chemotherapy against non-Hodgkin lymphoma or anti-HCV therapy), who switched to a dual therapy with etravirine (ETR) plus raltegravir (RAL). Patients were required not to have prior virological failure or resistance to both drugs. After a median follow up of 722 days (473-1088: 53.3 patients-year), there were no cases of transient virological replication or failure. Only 1 patient left therapy at day 10 due to a grade 2 rash, and therefore efficacy by intent-to-treat analysis was 96% at 48 weeks. There were no cases of liver toxicity grade 3-4, and total cholesterol (TC) and triglycerides (TG) levels decrease significantly after initiation (TC, -17 mg/dl; p=0.01; TG, -42 mg/dl; p=0.01), as well as the TC/High density lipoprotein-cholesterol ratio (from 4.35 to 4.28). Geometric mean plasma trough level of RAL was 166 ng/ml (IQR, 40-249), well above the inhibitory concentration 90 (IC(90)). In conclusion, a novel dual therapy with ETR plus RAL is effective and well tolerated, and it could be an option to maintain durable viral suppression in hard-to-treat HIV-infected patients.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Piridazinas/administración & dosificación , Piridazinas/farmacocinética , Pirrolidinonas/administración & dosificación , Pirrolidinonas/farmacocinética , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Femenino , Estudios de Seguimiento , VIH/efectos de los fármacos , VIH/fisiología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Estudios Prospectivos , Piridazinas/efectos adversos , Piridazinas/farmacología , Pirimidinas , Pirrolidinonas/efectos adversos , Raltegravir Potásico , Carga Viral/efectos de los fármacosRESUMEN
OBJECTIVES: To assess the outcome of a dual regimen combining darunavir/ritonavir plus etravirine in a cohort of antiretroviral therapy (ART)-experienced patients. METHODS: A retrospective analysis was performed on all ART-experienced patients starting a darunavir/ritonavir plus etravirine regimen at the 3 clinics. Patients were stratified according to HIV RNA detectability (≥ 40 copies/mL) at baseline. Two efficacy endpoints were evaluated by Kaplan-Meier and Cox multivariable models: virological failure (confirmed HIV RNA ≥ 40 copies/mL after 6 months) and therapeutic failure (including virological failure and treatment discontinuation for any reason). RESULTS: Sixty-eight patients were included in the study. They had a median of 10.8 years on ART and 5 previous ART regimens; 61.3% showed primary protease inhibitor (PI) mutations and 70% showed previous non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure. HIV RNA was detectable in 34 (50%) patients. The median observation period was 21 (interquartile range [IQR], 11.9-25.1) months. After 24 months, 75.1% of the patients were still on the study regimen and 88.8% remained free from virological failure. Although a higher therapeutic failure rate was reported in patients with detectable viremia at baseline, only the immunological status revealed an independent predictive role. No differences in virological failure were observed according to HIV RNA detectability at baseline; a higher number of previous ART regimens was the only predictor. Discontinuation due to adverse events occurred in 5.9%. CONCLUSIONS: Darunavir/ritonavir plus etravirine regimen proved virological efficacy and safety in heavily pretreated patients with a high rate of virological success, even in patients who switched during virological failure.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Piridazinas/uso terapéutico , Ritonavir/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Fármacos Anti-VIH/administración & dosificación , Estudios de Cohortes , Darunavir , Combinación de Medicamentos , Farmacorresistencia Viral , Quimioterapia Combinada , Femenino , VIH/genética , Infecciones por VIH/epidemiología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nitrilos , Piridazinas/administración & dosificación , Piridazinas/efectos adversos , Pirimidinas , ARN Viral , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Resultado del TratamientoAsunto(s)
Fármacos Anti-VIH/farmacocinética , Ciclohexanos/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Lopinavir/farmacocinética , Ritonavir/farmacocinética , Semen/química , Triazoles/farmacocinética , Adulto , Fármacos Anti-VIH/administración & dosificación , Ciclohexanos/administración & dosificación , Humanos , Lopinavir/administración & dosificación , Masculino , Maraviroc , Persona de Mediana Edad , Plasma/química , Ritonavir/administración & dosificación , Triazoles/administración & dosificaciónRESUMEN
BACKGROUND: Clinical use of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) may be hampered by toxicity, interactions or resistance issues. Simple and effective antiretroviral regimens avoiding both drug classes may be needed for selected patients. METHODS: This was a prospective cohort study. Virologically suppressed patients on PI or NRTI regimens, with problems of tolerability, safety concerns due to comorbidities or risk of drug interactions for both PIs and NRTIs, were given the opportunity to switch their regimen to etravirine plus raltegravir. Patients were required not to have prior virological failure to raltegravir and if there was prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure, only patients in whom efficacy of etravirine could be anticipated through the Stanford Drug Resistance Database were included. Follow-up was scheduled for at least 48 weeks, unless the patient was lost to follow-up or discontinued therapy. RESULTS: Twenty-five patients were included. Their median age was 54 years; they had a median of 16 years on antiretroviral therapy and a median of nine previous regimens; 21 (84%) patients had previous virological failure; and 15 (60%) patients had a genotypic test that showed three or more NRTI mutations in 9 (36%), four or more PI mutations in 11 (44%) and at least one NNRTI mutation in 8 (32%) patients. At 48 weeks efficacy was 84% (95% CI 65.3%-93.6%) by intent-to-treat analysis and 91.3% (95% CI 73.2%-97.6%) by per-protocol analysis. One (4%) patient died, two (8%) discontinued due to intolerance and one (4%) experienced virological failure. The CD4/CD8 ratio and plasma lipids improved. CONCLUSIONS: Dual therapy with etravirine plus raltegravir was well tolerated and maintained durable viral suppression in selected virologically suppressed patients for whom both PI and NRTI therapy was challenging.
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Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Piridazinas/administración & dosificación , Pirrolidinonas/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nitrilos , Proyectos Piloto , Estudios Prospectivos , Piridazinas/efectos adversos , Pirimidinas , Pirrolidinonas/efectos adversos , Raltegravir Potásico , Resultado del Tratamiento , Carga ViralAsunto(s)
Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Ciclohexanos/administración & dosificación , Ciclohexanos/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Triazoles/administración & dosificación , Triazoles/farmacocinética , Adulto , Quimioterapia Combinada/métodos , Humanos , Lopinavir/administración & dosificación , Masculino , Maraviroc , Plasma/química , Ritonavir/administración & dosificación , Factores de TiempoRESUMEN
BACKGROUND: Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery. METHODS: This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/ritonavir plus abacavir/lamivudine versus lopinavir/ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007). RESULTS: Of 95 patients included, 88 were randomized to lopinavir/ritonavir plus abacavir/lamivudine (nâ=â44) or lopinavir/ritonavir monotherapy (nâ=â44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/ritonavir plus abacavir/lamivudine, Pâ=â0.09/0.07, versus +215/+416 g in the lopinavir/ritonavir monotherapy group, Pâ=â0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)]. CONCLUSIONS: In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.