emtricitabine--tenofovir-disoproxil-fumarate-drug-combination and abacavir--lamivudine-drug-combination

Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety.. To compare the efficacy and safety of these three combinations.. Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC).. Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC.. The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.. El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad.. Comparar la eficacia y seguridad de las 3 combinaciones.. Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC).. Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC.. Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Lamivudine; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Zidovudine

The aim of this study was to investigate the effect on fasting lipid parameters of switching to tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) from abacavir (ABC) plus lamivudine (3TC; both fixed-dose combinations), while maintaining ritonavir-boosted lopinavir (LPV/r).. This was an open-label randomized two-arm 12-week controlled study in virologically suppressed HIV-infected patients with elevated cholesterol (≥5.2 mmol/l). Patients stable on ABC/3TC plus LPV/r either continued treatment or switched to TDF/FTC plus LPV/r for 12 weeks. Standard efficacy and safety end points (including fasting lipids) were assessed.. In total, 85 subjects were treated (n=42 ABC/FTC and n=43 TDF/3TC). A statistically significant decrease in total cholesterol was observed in the TDF/FTC group: from median (IQR) 6.22 mmol/l (5.91-6.77) at baseline to 5.75 mmol/l (5.04-6.18) at week 12 (median [IQR] change from baseline -0.73 mmol/l [-1.20- -0.18]; P<0.001). No notable change was observed for the ABC/3TC group. The difference between groups at week 12 was -0.82 mmol/l (P<0.001). For TDF/FTC (but not for ABC/3TC), statistically significant reductions (P<0.05) from baseline were observed in total, low-density lipoprotein, high-density lipoprotein (HDL)- and non-HDL cholesterol (at weeks 4 and 12). Statistically significant decreases were observed in median estimated creatinine clearance (Cockcroft-Gault) from baseline to week 12 for patients who switched to TDF/FTC (-5.47 ml/min) versus the ABC/3TC group (-2.15 ml/min; P=0.016 between groups). Virological suppression was maintained in both groups. No new safety issues were identified.. Switching to TDF/FTC from ABC/3TC was associated with rapid improvements in fasting lipid parameters and continued virological control in patients receiving LPV/r as the third component of antiretroviral therapy. The effect of these changes on clinical end points remains unclear and would need to be evaluated in a longer-term study.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cholesterol; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug Substitution; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Humans; Lamivudine; Lipids; Lopinavir; Male; Medication Adherence; Middle Aged; Organophosphorus Compounds; Ritonavir; Treatment Outcome

Topics: Anti-Retroviral Agents; Clinical Trials as Topic; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Lamivudine; Organophosphorus Compounds; Viral Load

Abacavir/lamivudine (Epzicom) and emtricitabine/tenofovir (Truvada), two new once-daily fixed-dose NRTI combinations, have been approved for use in antiretroviral regimens to treat HIV infection. Epzicom appears to be as effective as its components taken separately and, in one study, Truvada was at least as effective as zidovudine/lamivudine (Combivir). Use of once-daily fixed-dose combinations means less flexibility in dosing, and some patients with hepatic or renal impairment will not be able to take them.

Topics: Anti-HIV Agents; Deoxycytidine; Dideoxynucleosides; Dose-Response Relationship, Drug; Drug Combinations; Drug Hypersensitivity; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Lamivudine; Organophosphorus Compounds

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Deoxycytidine; Dideoxynucleosides; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Humans; Lamivudine; Organophosphorus Compounds; United States; United States Food and Drug Administration