JAIDS Journal of Acquired Immune Deficiency Syndromes:
Tenofovir Disoproxil Fumarate, Emtricitabine, and Efavirenz Versus Fixed-Dose Zidovudine/Lamivudine and Efavirenz in Antiretroviral-Naive Patients: Virologic, Immunologic, and Morphologic Changes-A 96-Week Analysis
Pozniak, Anton L MD*; Gallant, Joel E MD, MPH†; DeJesus, Edwin MD‡; Arribas, Jose R MD§; Gazzard, Brian MD*; Campo, Rafael E MD‖; Chen, Shan-Shan MPH¶; McColl, Damian PhD¶; Enejosa, Jeffrey MD¶; Toole, John J MD, PhD¶; Cheng, Andrew K MD, PhD¶; for the Study 934 Group
From the *Chelsea and Westminster Hospital, London, United Kingdom; †Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD; ‡Orlando Immunology Center, Orlando, FL; §Hospital de La Paz, Madrid, Spain; ‖University of Miami, Miami, FL; and ¶Gilead Sciences, Foster City, CA.
Received for publication June 12, 2006; accepted September 12, 2006.
Funded by Gilead Sciences.
A. L. Pozniak and J. R. Arribas report receiving consulting and lecture fees from Bristol-Myers Squibb (BMS), Gilead Sciences, and GlaxoSmithKline (GSK). J. E. Gallant reports receiving consulting and/or lecture fees from BMS, Gilead Sciences, and GSK, and receives grant support from Boehringer Ingelheim (BI), BMS, and Gilead Sciences. E. DeJesus and B. Gazzard have received consulting and lecture fees from BI, BMS, Gilead Sciences, and GSK. R. E. Campo reports receiving consulting fees from Gilead Sciences and grant support from Gilead Sciences and BMS. S.-S. Chen, A. K. Cheng, J. Enejosa, D. McColl, and J. J. Toole are employees and stockholders of Gilead Sciences.
Reprints: Andrew K. Cheng, MD, PhD, Gilead Sciences, 300 Lakeside Drive, Foster City, CA 94404 (e-mail: email@example.com).
Background: In antiretroviral-naive patients, tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) demonstrated superior outcomes compared with fixed-dose zidovudine (ZDV)/lamivudine (3TC) and EFV through 48 weeks. Results through a 96-week extension phase are presented.
Methods: In this randomized, open-label, noninferiority trial, 517 antiretroviral-naive HIV-infected patients received TDF, FTC, and EFV (TDF + FTC + EFV) or ZDV/3TC and EFV (ZDV/3TC + EFV). The primary endpoint was the proportion of patients with an HIV RNA level <400 copies/mL in patients without baseline nonnucleoside resistance.
Results: Through week 96, significantly more patients receiving TDF + FTC + EFV achieved and maintained an HIV RNA level <400 copies/mL (75% receiving TDF + FTC + EFV vs. 62% receiving ZDV/3TC + EFV; P = 0.004). There was a trend toward greater virologic suppression to <50 copies/mL in the TDF + FTC + EFV group (67% vs. 61%; P = 0.16). The TDF + FTC + EFV group demonstrated a significantly greater increase in CD4 count (270 vs. 237 cells/mm3; P = 0.036). No patient developed the K65R mutation. Limb fat at week 96 was significantly greater in the TDF + FTC + EFV group versus the ZDV/3TC + EFV group (7.7 vs. 5.5 kg; P < 0.001).
Conclusion: Over 96 weeks, the combination of TDF, FTC, and EFV was superior to fixed-dose ZDV/3TC + EFV for achieving and maintaining an HIV RNA level <400 copies/mL and an increase in CD4 cells.
Decreases in mortality have occurred in HIV-infected patients since the introduction of highly active antiretroviral therapy (HAART) more than 10 years ago.1 Multiple adult HIV treatment guidelines recommend the following as initial antiretroviral therapy: efavirenz (EFV) combined with zidovudine (ZDV) or tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC).2-5 Because most HIV-infected patients are likely to require prolonged and continuous antiretroviral therapy, there is a need for simpler, once-daily, well-tolerated regimens with minimal long-term toxicity and durable efficacy. This report examines the efficacy and tolerability of 2 regimens composed of EFV plus twice-daily fixed-dose ZDV/3TC or once-daily TDF and FTC over 96 weeks from an extension phase of study 934.
Design of Study
The complete details for the study design have been previously reported.6 An institutional review board or ethics committee approved the study protocol and informed consent form at each site. Each participant gave written informed consent at the beginning of the study and, again, to continue in the extension phase from week 48 through week 96. In brief, antiretroviral-naive adults with HIV-1 RNA levels >10,000 copies/mL regardless of CD4 cell count were randomized to receive a once-daily regimen of 600 mg of EFV, 300 mg of TDF, and 200 mg of FTC or 600 mg of EFV and a fixed dose combination of 300 mg of ZDV and 150 mg of 3TC twice a day. At screening, patients were required to have an estimated glomerular filtration rate (GFR; by the Cockcroft-Gault [CG] equation7) >50 mL/min. Patients who were not receiving randomized study medications did not participate in the study past week 48. The comparative portion of the trial was extended to 144 weeks.
Clinical examinations and laboratory analyses were conducted every 12 weeks from week 48 through week 96. A physical examination and assessment of adherence based on pill counts were performed at each visit. At week 48, whole-body dual-energy x-ray absorptiometry (DEXA) assessments of body fat composition were performed in a subset of patients (n = 100), whereas at week 96, all patients were asked to have whole-body DEXA scans that were read centrally in a blinded fashion.
The primary objective was to assess the noninferiority of TDF + FTC + EFV compared with ZDV/3TC + EFV as measured by an HIV RNA level <400 copies/mL through week 48. The secondary objectives of efficacy were to assess the noninferiority of TDF + FTC + EFV compared with ZDV/3TC + EFV at week 96 by an HIV RNA level <50 copies/mL and <400 copies/mL and by changes in CD4 cell counts.
All patients who received at least 1 dose of study medication were included in the safety analysis, which evaluated events that occurred after initiation of the study regimen to within 30 days after discontinuation of the regimen. The severity of adverse events and laboratory abnormalities was graded according to modified common toxicity criteria of the National Institutes of Allergy and Infectious Diseases.8
The primary outcome measures have been previously published.6 In brief, the efficacy endpoint, an HIV RNA level <400 copies/mL, was defined by the time to loss of virologic response (TLOVR) algorithm of the US Food and Drug Administration.9 The TDF + FTC + EFV group was considered noninferior to the ZDV/3TC + EFV group if the lower bound of the 2-sided 95% confidence interval (CI) for the difference between groups (TDF + FTC + EFV − ZDV/3TC + EFV) was −13% or more. Twenty-two patients with baseline resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) were excluded from the primary endpoint analysis.6 Additionally, 24 patients (12 from each from group) who completed the week 48 study with an HIV RNA level <400 copies/mL but did not consent to participate in the study extension from weeks 48 through 96 were also excluded. Thus, we report efficacy on 463 randomized patients. The 2 treatment groups were compared using the Cochran-Mantel-Haenszel test for TLOVR endpoints, Fisher exact test for other categoric data, and Wilcoxon rank sum test for continuous data. Analyses of CD4 cell count and safety laboratory data included patients who were on the randomized regimen. All statistical analyses were performed using SAS version 8.2 (SAS Institute, Cary, NC) at Gilead Sciences. There were no stopping rules. All reported P values are 2-sided and not adjusted for multiple testing.
Genotypic and phenotypic resistance analyses were also performed for patients who (1) continued study drugs and had ≥400 copies/mL of HIV RNA on at least 2 consecutive visits after achieving <400 copies/mL (viral rebound) on at least 1 occasion, (2) continued study drugs and had ≥400 copies/mL at week 96, or (3) discontinued study drugs before week 96 and had ≥400 copies/mL of HIV RNA on their last study visit (before discontinuing study drugs).
The demographic data have been published previously.6 As shown in Figure 1 and Table 1, through 96 weeks, significantly more patients achieved and maintained virologic suppression on TDF + FTC + EFV (75%) compared with those on ZDV/3TC + EFV (62%) using an HIV RNA level <400 copies/mL (P = 0.004; 95% CI for the difference between the 2 groups: 4% to 21%). A higher percentage of patients receiving TDF + FTC + EFV also had an HIV RNA level <50 copies/mL (67% vs. 61%; P = 0.16; 95% CI: −2% to 15%), but the difference did not achieve statistical significance. In the TDF + FTC + EFV group, there were 17 patients who achieved and maintained an HIV RNA level <400 copies/mL but failed to achieve and maintain a level <50 copies/mL. At week 96, 13 of these 17 patients had HIV RNA levels <100 copies/mL (6 of 17 had HIV RNA levels <50 copies/mL).
At week 96, the patients treated with TDF + FTC + EFV experienced significantly greater increases from baseline in absolute CD4 cell counts than the patients given ZDV/3TC + EFV (mean increase of 270 vs. 237 cells/mm3; P = 0.036) (see Figure 2). As measured by pill counts, the mean adherence to treatment was similar between groups (89% for the TDF + FTC + EFV group vs. 87% for the ZDV/3TC + EFV group; P = 0.13).
Significantly more patients discontinued the study in the ZDV/3TC + EFV group (see Table 1). As seen at week 48, there continued to be a significantly greater number of patients receiving ZDV/3TC + EFV who discontinued because of adverse events. Unlike the situation at week 48, however, there was a significant difference in virologic rebound (defined as having a confirmed HIV RNA level >400 copies/mL after achieving <400 copies/mL on 1 occasion) between the ZDV/3TC + EFV group (12 [5%] of 231 patients) compared with the TDF + FTC + EFV group (2 [<1%] of 232 patients; P = 0.007). The number of patients who discontinued the study for reasons other than virologic failure, pregnancy, death, and adverse events was similar between the groups from weeks 48 through 96 (18 patients in the TDF + FTC + EFV group vs. 14 patients in the ZDV/3TC + EFV group).
Through 96 weeks, 43 patients (29 in the ZDV/3TC + EFV group vs. 14 in the TDF + FTC + EFV group) met criteria for resistance testing, yielding 41 genotypes (2 patients in the ZDV/3TC + EFV group failed for technical reasons; Table 2). The K65R mutation, which can be selected by tenofovir, did not arise in any patient. Between weeks 48 and 96, 2 additional patients in the ZDV/3TC + EFV group developed the M184V/I mutation. Thus, at week 96, there was a significant difference between the 2 groups in the development of the M184V mutation, which was observed in 2 patients in the TDF + FTC + EFV group compared with 9 in the ZDV/3TC + EFV group (P = 0.036). One patient in the ZDV/3TC + EFV group developed the K70R mutation, a thymidine analogue mutation. EFV resistance was the most common form of resistance that developed in both groups; the most common form of EFV resistance observed was the K103N mutation. There was no significant difference in the frequency of EFV resistance development between groups.
Safety and Tolerability
The safety population comprised 511 patients who received any study medications. Grade 2 through 4 adverse events (regardless of relation to study drug) were observed in 185 (72%) of 257 patients in the TDF + FTC + EFV group and in 180 (71%) of 254 patients in the ZDV/3TC + EFV group (Table 3). Grade 2 through 4 laboratory abnormalities arose in 160 (63%) of 254 patients in the TDF + FTC + EFV group and in 160 (64%) of 251 patients in the ZDV/3TC + EFV group (see Table 3).
Through 96 weeks, significantly more patients in the ZDV/3TC + EFV group experienced adverse events that resulted in discontinuation of study medications (11% in the ZDV/3TC + EFV group vs. 5% in the TDF + FTC + EFV group; P = 0.008). The adverse events that led to discontinuation in at least 2% of patients in either group include the following: anemia (6% in the ZDV/3TC + EFV group vs. 0% in the TDF + FTC + EFV group), fatigue (2% in the ZDV/3TC + EFV group vs. 0% in the TDF + FTC + EFV group), nausea (2% in the ZDV/3TC + EFV group vs. <1% in the TDF + FTC + EFV group), and rash (<1% in the ZDV/3TC + EFV group vs. 2% in the TDF + FTC + EFV group). Few additional patients discontinued because of adverse events from weeks 48 through 96: 5 in the ZDV/3TC + EFV group and 2 in the TDF + FTC + EFV group. No patient discontinued because of anemia from weeks 48 through 96.
The 2 treatment groups had comparable renal safety over the 96-week study; no patients discontinued the study drug because of renal events. The median GFR, as estimated by the CG equation or modification of diet in renal disease10 (MDRD) equation, demonstrated decreases from baseline to week 96 in both groups (CG equation in mL/min: −1.5 in the TDF + FTC + EFV group vs. −0.3 in the ZDV/3TC + EFV group; P = 0.51 and MDRD in mL/min per 1.73m2: −1.7 in the TDF + FTC + EFV group vs. −1.1 in the ZDV/3TC+EFV group; P = 0.006). Among patients who had baseline mild renal dysfunction (<80 mL/min), the median increase in the GFR from baseline to week 96 was similar (in mL/min: 6.4 in the TDF + FTC + EFV group vs. 2.5 in the ZDV/3TC + EFV group; P = 0.79). Among those with an estimated GFR >80 mL/min at baseline, the median decrease in the GFR from baseline to week 96 was also similar (in mL/min: −2.6 in the TDF + FTC + EFV group vs. −0.6 in the ZDV/3TC + EFV group; P = 0.41) There were no confirmed grade 1 through 4 abnormalities in serum creatinine in the TDF + FTC + EFV group compared with 2 (<1%) patients (grades 1 and 2) in the ZDV/3TC + EFV group. There were no cases of Fanconi syndrome.
Patients who received TDF + FTC + EFV had a lower mean increase in fasting total cholesterol (25 mg/dL in the TDF + FTC + EFV group vs. 38 mg/dL in the ZDV/3TC + EFV group; P < 0.001). Similar fasting low-density lipoprotein (LDL) cholesterol levels were seen between groups (18 mg/dL in the TDF + FTC + EFV group vs. 24 mg/dL in the ZDV/3TC + EFV group; P = 0.067). The increase from baseline in fasting high-density lipoprotein (HDL) levels was significantly lower in the TDF + FTC + EFV group (10 mg/dL in the TDF + FTC + EFV group vs. 13 mg/dL in the ZDV/3TC + EFV group; P = 0.022). The increase from baseline in the mean fasting triglycerides was not significantly different between the 2 treatment groups (0 mg/dL in the TDF + FTC + EFV group vs. 30 mg/dL in the ZDV/3TC + EFV group; P = 0.115).
Using whole-body DEXA, patients at week 96 receiving ZDV/3TC + EFV had significantly less median total fat and total limb fat than those receiving TDF + FTC + EFV (Table 4). The 2 groups had a similar amount of trunk fat at week 96. Among patients who had DEXA scans at weeks 48 and 96, a significant median loss in limb fat in the ZDV/3TC + EFV group (n = 44) was observed (−0.7 kg; P = 0.001), whereas in the TDF + FTC + EFV group (n = 49), there was a significant median gain in limb fat (0.3 kg; P = 0.01; Fig. 3). Through 96 weeks, patients receiving TDF + FTC + EFV had a significantly greater median increase from baseline in weight of 2.7 kg compared with 0.5 kg in patients receiving ZDV/3TC + EFV (P < 0.001). Notably, both groups entered the trial with a similar median weight.
A superior virologic response was demonstrated for the TDF + FTC + EFV group for the proportion of patients with an HIV RNA level <400 copies/mL at 96 weeks. In contrast to week 48, there was no statistical difference demonstrated for an HIV RNA level <50 copies/mL. The difference between the week 48 and week 96 results is partially accounted for by patients who had 2 consecutive viral loads between weeks 48 and 96 >50 copies/mL but remaining <400 copies/mL.
One concern regarding interpretation of trial results from open-label studies is the potential for bias when discontinuations for nonobjective reasons play a role in the study outcome. It is notable that the discontinuations for events other than adverse events, virologic failure, pregnancy, or death were similar between groups during weeks 48 through 96, however.
A significant difference was seen in the proportion of patients receiving ZDV/3TC + EFV who developed virologic rebound (confirmed HIV RNA level >400 copies/mL) or the M184V/I mutation from baseline through week 96. In study 903, a double-blind antiretroviral-naive trial of TDF, 3TC, and EFV versus stavudine (d4T), 3TC, and EFV, 39% (14 of 36) and 22% (8 of 36) of patients with genotypes in the TDF group developed the M184V/I and K65R mutations through 96 weeks, respectively.11 In this study, however, 14% (2 of 14) of genotyped patients receiving TDF, FTC, and EFV developed the M184V/I mutation and no patient developed the K65R mutation through 96 weeks. The similarly long intracellular half-life of tenofovir diphosphate and FTC triphosphate may have contributed to the resistance findings observed in this study.12,13 Drug penetration into sanctuary sites, which is unknown for some of the agents studied, may also have contributed to the findings. Single mutations lead to large decreases in susceptibility for 3TC, FTC, and EFV, whereas a single mutation leads to much lower decreases in susceptibility for tenofovir. Multiple mutations are required for full loss of susceptibility to ZDV. The 96-week resistance findings from this study, particularly the difference with M184V development, demonstrate how outcomes differ for regimens compared with individual agents.
Renal adverse events were uncommon in this trial, which is consistent with the 48-week results and results from other reported randomized clinical trials involving TDF in treatment-naive and treatment-experienced patients6,11,14,15
One of the limitations of the study is the absence of baseline DEXA scans, which hampers our ability to make accurate longitudinal interpretations. At week 64 in the 5005 substudy of AIDS Clinical Trial Group (ACTG) 384, patients receiving ZDV/3TC (n = 41) with nelfinavir or EFV demonstrated a median 4.0% (approximately 0.3 kg) gain of limb fat from baseline.16 Among the 280 patients in this trial who underwent DEXA scanning at week 96, those receiving TDF + FTC + EFV had significantly more total limb fat (2.2-kg difference between groups) than those receiving ZDV/3TC + EFV. Of note, in study 903 at week 96, the TDF + 3TC + EFV group (n = 128) also demonstrated significantly more total limb fat (2.6-kg difference in median limb fat) than the d4T + 3TC + EFV group (n = 134).11 In study 903 at week 144, the significant difference in median total limb fat between the 2 groups increased to 3.6 kg.11 Whether we are likely to see a larger difference in total limb fat at week 144 in this trial is unknown. Nevertheless, the loss of 0.7 kg of total limb fat observed in the subset of patients receiving ZDV/3TC + EFV with week 48 and week 96 data is noteworthy, given the absence of effective nonsurgical treatments for lipoatrophy and the slow and possibly incomplete recovery of limb fat after changing antiretroviral therapy.17-19 The results from week 48 and week 96 indicate an advantage of the TDF + FTC nucleoside backbone with respect to lipoatrophy.
In starting therapy for antiretroviral-naive patients, it is important to minimize the risk of side effects and long-term toxicity, especially those that are difficult to reverse, such as lipoatrophy. The combination of 3TC and ZDV has been a preferred nucleoside backbone for several years. It has been shown in this study and others that starting patients on ZDV increases the risk of short- and long-term side effects compared with the use of alternative agents such as TDF. Long-term follow-up of antiretroviral-naive patients entering clinical trials and randomized to TDF has demonstrated a similar renal safety profile compared with controls out to 3 years.11 EFV, FTC, and TDF were administered as individual agents in this trial, but a fixed-dose combination of TDF + FTC + EFV is now available and may promote better adherence to antiretroviral therapy. Because once-daily therapy is now a reality, the use of ZDV with its twice-daily dosing and side effect profile is likely to become less acceptable to physicians and patients. The durable antiviral response, favorable resistance profile, and excellent safety profile of the TDF + FTC + EFV group in this study provides continued support for the use of this regimen in antiretroviral therapy-naive patients.
The authors are grateful to the patients who participated in the study. In addition to the authors, the names of the members of the Study 934 Group have been previously published.6
1. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med
2. Hammer SM, Saag MS, Schechter M, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA Panel. JAMA
3. US Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at: http://AIDSinfo.nih.gov
. Accessed October 6, 2006.
4. Gazzard B. Writing Committee British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Med
. 2005;(Suppl 2):1-61.
5. Carosi G, Torti C, Andreoni M, et al. Key questions in antiretroviral therapy: Italian Consensus Workshop (2005). J Antimicrob Chemother
6. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine and efavirenz vs. zidovudine, lamivudine and efavirenz for HIV. N Engl J Med
7. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron
8. National Institutes of Allergy and Infectious Diseases. Division of AIDS table of grading severity of adult adverse experiences. 1992. Available at: http://rcc.tech-res-intl.com/
. Accessed October 6, 2006.
9. US Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for industry: antiretroviral drugs using plasma HIV RNA measurements-clinical considerations for accelerated and traditional approval. 2002. Available at: http://www.fda.gov/cder/guidance
. Accessed October 6, 2006.
10. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med
11. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs. stavudine in combination therapy in antiretroviral naïve patients: a 3 year randomized trial. JAMA
12. Hawkins T, Veikley W, St. Claire RL, et al. Intracellular pharmacokinetics of tenofovir diphosphate, carbovir triphosphate, and lamivudine triphosphate in patients receiving triple-nucleoside regimens. J Acquir Immune Defic Syndr
13. Wang LH, Begley J, St. Clair RL, et al. Pharmacokinetic and pharmacodynamic characteristics of emtricitabine support its once daily dosing for the treatment of HIV infection. AIDS Res Hum Retroviruses
14. Johnson M, Grinsztejn B, Rodriguez C, et al. 96-Week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS
15. Molina JM, Wilkin A, Domingo P, et al. Once daily vs. twice daily lopinavir/ritonavir in antiretroviral naïve patients: 96 week results. Presented at: Third International AIDS Society Conference on HIV Pathogenesis and Treatment; 2005; Rio de Janeiro.
16. Dube MP, Parker RA, Tebas P, et al. Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides. AIDS
17. McComsey GA, Ward DJ, Hessenthaler SM, et al. Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Clin Infect Dis
18. Martin A, Smith DE, Carr A, et al. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from thymidine analogue to abacavir: the MITOX Extension Study. AIDS
19. Moyle G, Sabin C, Cartledge J, et al. A 48 week, randomized, open-label comparative study of tenofovir DF vs. abacavir as substitutes for a thymidine analog in persons with lipoatrophy and sustained virologic suppression of HAART [abstract 44LB]. Presented at: 12th Conference on Retroviruses and Opportunistic Infections; 2005; Boston.
This article has been cited 77 time(s).
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antiretroviral naive; emtricitabine; lamivudine; lipoatrophy; tenofovir; zidovudine
© 2006 Lippincott Williams & Wilkins, Inc.
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