Tenofovir Disoproxil Fumarate, Emtricitabine, and Efavirenz Compared With Zidovudine/Lamivudine and Efavirenz in Treatment-Naive Patients

Internal Medicine Service, Hospital de La Paz, Madrid, Spain.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 01/2008; 47(1):74-8. DOI: 10.1097/QAI.0b013e31815acab8
Source: PubMed


As antiretroviral regimens for the treatment of HIV infection improve, trials providing data on long-term follow-up are increasingly important.
A regimen of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) demonstrated superior virologic, immunologic and morphologic effects compared with a regimen of fixed-dose zidovudine/lamivudine (ZDV/3TC) and EFV through 96 weeks in a randomized open-label trial. After 96 weeks, patients on TDF + FTC transitioned to fixed-dose combination TDF/FTC.
Through 144 weeks, significantly more patients in the TDF/FTC arm reached and maintained an HIV RNA level <400 copies/mL (71% receiving TDF/FTC and EFV vs. 58% receiving ZDV/3TC and EFV; P = 0.004), with a trend toward greater CD4 cell increase in the TDF/FTC arm (312 vs. 271 cells/mm; P = 0.09). Over 144 weeks of follow-up, more patients in the ZDV/3TC arm discontinued therapy because of adverse events (11% vs. 5%; P = 0.01) and no patients discontinued because of renal events. Patients in the ZDV/3TC arm had significantly less limb fat than patients in the TDF/FTC arm (5.4 vs. 7.9 kg; P < 0.001) at 144 weeks.
Cumulative results from 3 years of follow-up suggest that a regimen of TDF/FTC and EFV demonstrates superior durability of viral load suppression and an improved safety and morphologic profile compared with ZDV/3TC and EFV.

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Available from: Joel E. Gallant, Dec 26, 2013
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    • "Small case series and observational studies first described TDF-related nephrotoxicity (Mauss et al., 2005; Malik et al., 2005; Zimmermann et al., 2006). Although early clinical trials showed similar rates of nephrotoxicity between TDF and non-TDF controls (Gallant et al., 2004; Arribas et al., 2008), newer long-term studies found mild-moderate nephrotoxicity with consistent TDF use (Monteagudo-Cho et al., 2012). TDF has had a good safety profile, with low absolute rates of renal dysfunction or adverse events in treatment-naïve and experienced patients (Jones et al., 2004; Moreno et al., 2006; Guaraldi et al., 2009). "

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    • "The percentage distribution of patients considered in the model with respect to the proposed CD4 cell count takes into account observations on HIV infection/AIDS in Emilia Romagna (epidemics update as of December 31, 2009). The immunologic response to each of the two therapeutic study regimens, ie, TDF-FTC + EFV (multipill regimen) and the single-tablet regimen, was considered comparable, with 80% response rates in the first year, 67% in the second year, 64% in the third year, and 64% in the following years throughout ten observation years.20–22 When data were not available, it was assumed that the response remained constant at the last observed value by applying the last value carried forward technique. "
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    ABSTRACT: The aim of this study was to assess the economic value of a reduced number of pills in patients infected with the immunodeficiency virus (HIV) and on highly active antiretroviral therapy by a cost-effectiveness model. An incremental cost-effectiveness analysis of efavirenz, tenofovir, and emtricitabine (TDF-FTC-EFV) as a single-tablet regimen versus a multipill regimen, with reference to untreated HIV-infected patients, was carried out from the perspective of the Italian National Health Service. The comparisons were performed with the help of a Markov decision model over a 10-year time horizon. Based on the ADONE (ADherence to ONE pill) study, it was then possible to identify the utility score increment in patients switching from a multipill regimen of TDF-FTC + EFV therapy to a single-tablet regimen. The single-tablet regimen (0.755 quality-adjusted life-years [QALYs]/year) resulted in better patient quality of life, with a higher number of QALYs than for the TDF-FTC + EFV multipill regimen (0.716 QALYs/year). The single-tablet regimen was the most cost-effective treatment strategy, with an incremental cost-effectiveness ratio of €22,017.00 versus €26,558.00 for the multipill regimen. A 24% decrease in cost of the multipill regimen determined equivalence with the single-tablet regimen in terms of the incremental cost-effectiveness ratio. Univariate sensitivity and probabilistic analysis carried out on the main variables did not highlight significant variations with respect to the base case scenario. The single-tablet regimen resulted in better adherence, and therefore better quality of life as perceived by patients, corresponding to a €4541.00 lower cost-effectiveness ratio per QALY versus the multipill regimen, with a 17% lower cost in favor of the single-tablet regimen. The value determined could be used to identify a maximum potential "premium price" of 29% to be assigned to therapeutic regimens proposing a single-tablet regimen for HIV-infected patients.
    Full-text · Article · Feb 2013 · ClinicoEconomics and Outcomes Research
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    • "The association of TDF and renal dysfunction has remained an area of interest. In several clinical trials, TDF has been found to be safe with renal effects reported to be 1-3% with minimal differences from comparative non TDF arms [4-7]. However, several case reports and series show patients treated with TDF may present with acute renal failure, Fanconi syndrome and diabetes insipidus. "
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    ABSTRACT: Tenofovirdisoproxilfumarate (TDF) is a nucleotide analogue widely recommended in international HIV treatment guidelines. The association of TDF and renal dysfunction has remained an area of interest. We conducted a retrospective review of all patients on TDF from July 2007 to December 2009 in our institution and evaluated their renal function. Absolute change of creatinine clearance (CLCr) using Cockroft-Gault equation from baseline was calculated at 6, 12, 18 and 24 months. Overall, 226 patients were included in the study. Ninety percent were male. The median age was 46 yrs old (23-82), median weight was 60 kg (IQR 53.75-68), median CD4 count was 127 cells/mm3 (IQR 38-258) and median CLCr 82.7 mL/min (IQR 71.4-101.7) on initiation of TDF. The median decline of CLCr from baseline was -3.9 ml/min (IQR -12.3 to 7.6), and -3.6 ml/min (IQR -12.4 to 6.7) at 12 (n = 102), 24 months (n = 75) respectively. Eighteen of 226 patients had a decline in renal function to </=50 ml/min. Majority of which had an improvement of CLCr on follow up. Only 80% of patients ever received monitoring of renal function. While we noted renal toxicity to be rare and transient among our cohort receiving TDF as part of their ARV regimen, these results reflect the short term renal effects of TDF given that ARV treatment is lifelong. Given that laboratory monitoring may be difficult to implement in many situations, future prospective studies looking into an evidence based algorithm for less frequent renal function monitoring than current guideline recommendations may be helpful.
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