Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV

Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, United States
New England Journal of Medicine (Impact Factor: 54.42). 02/2006; 354(3):251-60. DOI: 10.1056/NEJMoa051871
Source: PubMed

ABSTRACT Durable suppression of replication of the human immunodeficiency virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere.
We conducted an open-label, noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were randomly assigned to receive either a regimen of tenofovir disoproxil fumarate (DF), emtricitabine, and efavirenz once daily (tenofovir-emtricitabine group) or a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily (zidovudine-lamivudine group). The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study.
Through week 48, significantly more patients in the tenofovir-emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine-lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P=0.002). This difference excludes the inferiority of the tenofovir DF, emtricitabine, and efavirenz regimen, indicating a significantly greater response with this regimen. Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter (80 percent in the tenofovir-emtricitabine group vs. 70 percent in the zidovudine-lamivudine group; 95 percent confidence interval for the difference, 2 to 17 percent; P=0.02) and in increases in CD4 cell counts (190 vs. 158 cells per cubic millimeter, respectively; 95 percent confidence interval for the difference, 9 to 55; P=0.002). More patients in the zidovudine-lamivudine group than in the tenofovir-emtricitabine group had adverse events resulting in discontinuation of the study drugs (9 percent vs. 4 percent, respectively; P=0.02). In none of the patients did the K65R mutation develop.
Through week 48, the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs. ( number, NCT00112047.)

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Available from: Joel E. Gallant, Aug 29, 2015
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    • "Whereas some negative effects on kidney function have been reported with indinavir, lopinavir/ritonavir, atazanavir, and ritonavir in the published literature,37,64,65 the antiretroviral associated with kidney impairment with the greatest frequency is tenofovir, a preferred medication according to the Department of Health and Human Services guidelines, and commonly used in clinical practice.45 In premarketing studies of tenofovir, there was no reported kidney impairment in its safety profile.66,67 However, following US Food and Drug Administration approval, a number of case reports surfaced describing a variety of toxic effects on the kidneys.68–84 "
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    ABSTRACT: The prevalence of human immunodeficiency virus (HIV) infection in older and elderly adults is significant worldwide. This population poses new challenges and opportunities in the management of HIV. In addition to the risks affecting HIV patients of all ages, including risk of opportunistic infection and medication resistance, age-related changes in physiology, higher comorbidity burdens, increased use of medications, and potential adverse drug reactions to HIV medications all factor into the care of older adults with HIV. The risk and progression of cardiovascular and renal comorbidities may be higher in the older adult HIV population and in patients taking specific HIV medications. Understanding these risks is essential when managing a new type of patient: the older adult with HIV.
    HIV/AIDS - Research and Palliative Care 09/2013; 5:263-274. DOI:10.2147/HIV.S36311
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    • "Por ejemplo, el estudio de Robbins et al., 2003 (26) reportó una proporción de pacientes con carga viral indetectable del 75%. Similarmente, en el estudio de Gallant et al., 2006 (27), diseñado con el objetivo de comparar un esquema basado en Tenofovir , Emtricitabina y Efavirenz versus el esquema Lamivudina/Zidovudina + Efavirenz, reportó en el brazo de control (Lamivudina/Zidovudina + Efavirenz) una proporción del 73% de los pacientes que lograron indetectabilidad de la carga viral. Por su parte, un estudio abierto con 19 pacientes con el esquema innovador Combivir ® + Stocrim ® realizado en Londres por Portsmouth S et al., 2004 (20), encontró que el tiempo medio para alcanzar una carga viral indetectable fue de 12 semanas (rango 4-36 semanas); tiempo que es similar al que se obtuvo en el presente estudio (12 semanas) (ver figura 2). "
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    ABSTRACT: Background: The strengthening of generic drugs policy may be accompanied by reservations about their quality, and therefore, also about effectiveness of some of these products. Phase IV clinical trials are a proper design to evaluate the effectiveness and safety of these drugs. Objective: Assess the effectiveness and the safety data of generic drug scheme Lamivudine/Zidovudine/Efavirenz in HIV (+) naïve patients who are served in a specialized comprehensive ambulatory care program, and compare these results with efficacy and safety data reported in reference studies (using the same therapeutic scheme of innovator drugs and conducted in patients with the same conditions). Methods: An open-label and non-controlled phase IV clinical trial was conducted. Effectiveness (measured as viral load reduction to undetectable level and lymphocytes CD4 + increase) and safety (adverse reactions) of the generic drug scheme Lamivudine/Zidovudine + Efavirenz were assessed. Antiretroviral therapy was used during 12 months in HIV (+) naïve patients over 18 years old who had the indication to treatment. Clinical follow-up and Pharmacotherapy follow-up were used as assessment strategies and data collection. Non-inferiority hypothesis was contrasted against the study results and those reported in a reference study. Results: The study included 47 patients, of which 33 completed the study. After one year of treatment, 28 patients (85%) achieved a statistically significant reduction in viral load (assessed by undetectable mRNA copies/mL), and 30 of them (91%) had a progressive and statistically significant increase in T- CD4 + lymphocyte count greater than 200 cells/mm3. The comparison was performed using an article that met the defined criteria, and non-inferiority hypothesis was proven. The proportions of patients [CI 95%] achieving undetectability was not statistically different when comparing with reference study: 0.85 [0.69 to 0.93] versus 0.90 [0.81 to 0.93], p = 0.7. Similarly, there was no difference in the average increase of CD4 + [SD]: 179 ± 142 versus 201 ± 21, p = 0.08. Likewise, No important differences in the safety profile were found. Conclusions: The generic drug scheme Lamivudine/Zidovudine/Efavirenz is effective and safe, and effectiveness outcomes achieved were not lower than those reported in reference studies designed to assess the same scheme of innovator drugs.
    Vitae 04/2013; 20(1):30-40. · 0.26 Impact Factor
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    • "The robust immunologic response of > 50 cells / mm3 was seen in 77.4% of patients at 12 months with a median CD4 cell count increase of 139 cells / mm3 which is consistent with results obtained in other programs in similar settings [26,27]. Since more than half of the entire patient cohort were on a Tenofovir-containing regimen which is known for its superiority, convenient dosing, low toxicity and high potency [28-30], we were expecting a lower virologic failure rate than 23%. However, there were no statistically significant differences in virologic suppression by baseline drug regimen among this study cohort. "
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    ABSTRACT: Background Predictors of immuno-virologic outcomes and discordance and their associations with clinical, demographic, socio-economic and behavioral risk factors are not well described in Nigeria since HIV viral load testing is not routinely offered in public HIV treatment programs. Methods The HACART study was a multi-center observational clinic-based cohort study of 2585 adults who started HAART between April 2008 and February 2009. A total of 628 patients were randomly selected at 12 months for immuno-virologic analyses. Results Virologic suppression rate (<400 copies/ml) was 76.7%, immunologic recovery rate (CD4 change from baseline ≥50 cells/mm3) was 77.4% and immuno-virologic discordance rate was 33%. In multivariate logistic regression, virologic failure was associated with age <30 years (OR 1.79; 95% CI: 1.17-2.67, p=0.03), anemia (Hemoglobin < 10 g/dl) (OR 1.71; 95% CI: 1.22-2.61, p=0.03), poor adherence (OR 3.82; 95% CI: 2.17-5.97, p=0.001), and post-secondary education (OR 0.60; 95% CI: 0.30-0.86, p=0.02). Immunologic failure was associated with male gender (OR 1.46; 95% CI: 1.04-2.45, p=0.04), and age <30 years (OR 1.50; 95% CI: 1.11-2.39, p=0.03). Virologic failure with immunologic success (VL-/CD4+) was associated with anemia (OR 1.80; 95% CI: 1.13-2.88, p=0.03), poor adherence (OR 3.90; 95% CI: 1.92-8.24, p=0.001), and post-secondary education (OR 0.40; 95% CI: 0.22-0.68, p=0.005). Conclusions Although favorable immuno-virologic outcomes could be achieved in this large ART program, immuno-virologic discordance was observed in a third of the patients. Focusing on intensified treatment preparation and adherence, young patients, males, persons with low educational status and most importantly baseline anemia assessment and management may help address predictors of poor immuno-virologic outcomes, and improve overall HIV program impact. Viral load testing in addition to the CD4 testing should be considered to identify, characterize and address negative immuno-virologic outcomes and discordance.
    BMC Infectious Diseases 03/2013; 13(1):113. DOI:10.1186/1471-2334-13-113 · 2.61 Impact Factor
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