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Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study

Schooley, Robert T.; Ruane, Petera; Myers, Robert A.b; Beall, Gildonc; Lampiris, Harryd; Berger, Daniele; Chen, Shan-Shanf; Miller, Michael D.f; Isaacson, Ericaf; Cheng, Andrew K.f; for the Study 902 Team

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From the University of Colorado, Denver, Colorado, aTower ID, Los Angeles, California, bBody Positive, Phoenix, Arizona, cHarbor-UCLA Medical Center, Torrance, Torrance, California dDepartment of Veterans Affairs Medical Center, San Francisco and University of California, San Francisco, California, eNorthstar Medical Center, Chicago, Illinois, fGilead Sciences, Foster City, California, USA.

Correspondence to A. Cheng, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404-1147, USA.

Received: 20 July 2001;

revised: 4 January 2002; accepted: 14 January 2002.

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Abstract

Objective: To evaluate the safety and efficacy of once daily doses of tenofovir DF (TDF) administered in combination with other antiretroviral therapy (ART) in treatment-experienced HIV-1-infected patients with incomplete virological suppression.

Design: One-hundred and eighty-nine subjects with plasma HIV-1 RNA levels between 400 and 100 000 copies/ml and stable ART (≥ 8 weeks) were randomized (2:2:2:1 ratio) to add TDF 75 mg, 150 mg, or 300 mg or placebo to existing ART in a double-blinded manner. After 24 weeks, patients initially randomized to placebo received blinded TDF 300 mg.

Methods: Efficacy was analyzed by the mean changes HIV-1 RNA levels (log10 copies/ml plasma; DAVGxx) from week 0 to weeks 4, 24, and 48. Safety was analyzed by incidence of grade 3 or 4 clinical and laboratory adverse events.

Results: At baseline, patients had mean 4.6 years prior ART use with 94% having HIV-1 with nucleoside-associated resistance mutations. There were statistically significant decreases in DAVG4 and DAVG24 for all doses of TDF compared with placebo, with the greatest effect seen with TDF 300 mg (DAVG4, −0.62, P < 0.001; DAVG24, −0.58;P < 0.001; DAVG48, −0.62). The incidence of adverse events was similar among the TDF groups and placebo through week 24. Throughout the 48-week study, no significant changes in renal function were observed.

Conclusions: In treatment-experienced patients with baseline nucleoside resistance mutations, TDF provided dose-related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of TDF was similar to that of placebo.

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Introduction

The current approach to treating HIV-1 infection is a regimen of highly active antiretroviral therapy (HAART), with the goal of suppressing plasma viral replication for as long as possible. Unfortunately, many patients do not achieve or sustain long-term virological suppression, which is a primary unmet need in the treatment of HIV-1 infection.

Tenofovir (PMPA) is an acyclic nucleotide reverse transcriptase inhibitor (NtRTI) with activity in vitro against HIV-1 and HIV-2 [1,2]. Further, tenofovir has a favorable resistance profile, as it is active against wild-type and most nucleoside-resistant HIV-1 strains [3,4]. In preclinical studies, the K65R mutation in reverse transcriptase was selected by tenofovir in vitro, resulting in a three- to fourfold decrease in susceptibility to tenofovir [3]. Although the K65R mutation can be selected by zalcitabine, abacavir and didanosine, in vitro or in vivo, its prevalence in treatment-experienced patients is rare (< 2%) [5]. Because the presence of a phosphonate group limits the oral bioavailability of tenofovir, a prodrug, tenofovir disoproxil fumarate (tenofovir DF), was developed, which is orally bioavailable and is rapidly converted to tenofovir following absorption [6].

This phase II study (GS-98-902) investigated the use of multiple doses of tenofovir DF in a population of treatment-experienced HIV-1-infected patients with evidence of suboptimal virological suppression. Three doses of tenofovir DF were evaluated (75 mg, 150 mg, and 300 mg), administered once daily in addition to the patient's existing antiretroviral regimen. These doses were chosen based on the phase I/II study, GS-97-901, during which four doses of tenofovir DF were evaluated (75 mg, 150 mg, 300 mg, and 600 mg) as monotherapy for 28 days [7]. No safety issues were identified in this short-term study, while the greatest antiviral response was seen in the antiretroviral-naive patients in the 300 mg arm: a median 1.6 log10 copies/ml reduction from baseline in plasma HIV-1 RNA. In the present study, antiviral efficacy and the durability of initial antiviral responses were also compared among the various groups in the study. This study consisted of a 48-week, double-blinded phase and an ongoing open-label phase. The results from the double-blinded phase of the study are presented.

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Methods

Study population and design

An Institutional Review Board reviewed the study protocol and consent form for each study center and all patients provided written informed consent. One-hundred and eighty-nine HIV-1 infected adults were enrolled into the study at 22 centers in the USA. Eligible patients had plasma HIV-1 RNA levels between 400 and 100 000 copies/ml and were on stable antiretroviral therapy (ART; no more than four agents) for at least 8 weeks prior to randomization. Patients were assigned randomly in a 2:2:2:1 ratio to add 75 mg, 150 mg, or 300 mg of tenofovir DF or identical appearing placebo once daily to their existing regimen in a double-blinded manner. Tenofovir DF was supplied by Gilead Sciences, Inc., as white to off-white, round, standard biconvex tablets containing 75 mg of the active ingredient. Placebo tablets matched the tenofovir DF tablets in physical appearance and contained denatonium benzoate to match the bitterness of the active tablets. Patients were encouraged to maintain their background antiretroviral regimen for at least 4 weeks post-randomization. Patients were stratified by site according to HIV-1 RNA level (< 20 000 or ≥ 20 000 copies/ml), CD4 cell count (< 200 × 106 or ≥ 200 × 106 cells/l), and the total number of antiretroviral drugs (< 4 or ≥ 4) used in past and current regimens at study entry. At 24 weeks post-randomization, patients initially assigned to the placebo arm were crossed over to tenofovir DF 300 mg once daily, in a blinded fashion, for the remainder of the study. After completing 48 weeks of the study, patients were given the option to continue to receive open-label tenofovir DF 300 mg once daily.

Interactive Clinical Technologies, Inc. (ICTI) was selected to develop and maintain an interactive voice response system (IVRS), which centralized patient randomization and drug dispensing. Through the IVRS system, ICTI generated the random allocation sequence, and enrolled and assigned patients to their treatment groups. In order to conceal the allocation sequence for the duration of the 48-week study, ICTI assigned patients with blinded kit numbers.

The co-primary efficacy end points were the time-weighted mean change in plasma HIV-1 RNA (log10 copies/ml) from baseline to weeks 4 (DAVG4) and 24 (DAVG24). In addition, the time-weighted mean change in HIV-1 RNA levels from baseline to week 48 (DAVG48) was assessed for the three active treatment groups. This parameter was used in lieu of traditional analyses (measuring only HIV-1 RNA changes from baseline) as DAVG reflects treatment experience with all patients and all data contributing to the endpoint. DAVG24 is defined as the subject's time-weighted mean marker value between baseline and week 24 minus the subject's baseline value. Specifically, if the AUC24 is the area-under-the-curve of log10 HIV-1 RNA copies/ml between baseline and week 24 (using the trapezoidal rule with available marker data between weeks 0 and 24 inclusive), then DAVG24 is defined as: [AUC24 − 24⋅Y0]/24 = DAVG24 where time is measured in weeks and Y0 denotes the value of log10 RNA copies/ml at time 0, taken to be the average of the prebaseline and baseline values. For subjects with marker data only through week w (w < 24), DAVG24 is taken to be [AUCw − w⋅Y0]/w. Similar measures were calculated using values at week 48.

The primary safety end-point was the percentage of patients with grade 3 or 4 abnormalities (clinical adverse events and laboratory toxicities occurring after treatment initiation through 30 days following administration of the last dose of study drug). Additional safety assessments included the effects of tenofovir DF on renal and bone parameters, organs that preclinical (animal) studies indicated may be areas of potential concern.

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Assessments

Unless otherwise specified, all referenced laboratory values were obtained from samples sent to a central laboratory. Plasma HIV-1 RNA level was assessed at the screening visit using the standard Amplicor HIV-1 Monitor Test [lower limit of quanitation (LLQ), 400 copies/ml] (Roche, Nutley, New Jersey, USA). Subsequently, plasma HIV-1 RNA levels were measured at prebaseline, baseline and at the end of weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48 using the Ultrasensitive HIV-1 Monitor Test (LLQ, 50 copies/ml) (Roche). CD4 cell counts were performed at screening, baseline and at the end of weeks 4, 8, 12, 24, 36, and 48. Plasma for genotypic analyses of the HIV-1 reverse transcriptase and protease genes was stored at the prebaseline, baseline and at the end of weeks 2, 4, 12, 16, 20, 24, 32, 40 and 48. Genotypic analyses were performed with HIV-1 TruGene technology (Visible Genetics, Toronto, Canada). Safety and tolerance were evaluated by assessing adverse events and clinical laboratory values at weeks 2, 4, 8 and every 4 weeks thereafter until completion of the study. Bone mineral density was assessed with dual-energy X-ray absorptiometry (DXA) scanning of the L1–L4 vertebral column every 3 months at selected centers.

Any adverse event with an onset date after study drug administration or within 30 days following study completion was recorded as an adverse event, regardless of the severity or relationship to study medication.

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Statistical analysis

A sample size of 50 patients per group for each of the tenofovir DF arms was calculated to provide at least 80% power to detect a 30% difference at the 5% significance level between the treatment groups using a two-sided test.

Data were analyzed for ‘intent-to-treat’ (ITT, missing = failure) populations. ITT was the primary population for all analyses of efficacy and baseline characteristics, which included data from all patients who were randomized into the study and received one dose of study medication with no data exclusions. The safety population included all patients who received at least one dose of the study medication.

Safety analyses included the percentage of patients who developed grade 3 or 4 toxicity (clinical and/or laboratory). Efficacy was analyzed as the time-weighted average change from baseline in log10 HIV-1 RNA copies/ml up to week 4 (DAVG4) and week 24 post-randomization (DAVG24). Pair-wise comparisons of treatment groups were based on the Wilcoxon rank sum test. P values < 0.05 were considered statistically significant.

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Results

Subject population

The study period lasted from 2 September 1998 (first patient randomized) to 16 March 2000 (final patient observation for 48-week blinded phase of study). One-hundred and eighty-nine adults were enrolled into the study: 54 subjects were assigned to the tenofovir DF 75 mg group, 51 to the tenofovir DF 150 mg group, 56 to the tenofovir DF 300 mg group, and 28 to the placebo group. The majority of patients in this study had symptomatic HIV-1 infection or AIDS. Baseline characteristics for the ITT population, which are summarized in Table 1, were similar in the four treatment arms. The overall mean plasma HIV-1 RNA level at entry was 3.7 log10 copies/ml and the overall mean CD4 count was 374 × 106 cells/l. There were no statistically significant differences between the groups in CD4 cell counts or HIV-1 RNA levels at baseline.

Table 1
Table 1
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Patients participating in this study had substantial prior exposure to ART, with an overall mean duration of 55 months. Almost all of the patients in this study had HIV-1 drug resistance mutations at baseline. The proportion harboring HIV with mutations was similar in all groups: 94% had resistance mutations associated with NRTI; 57% had primary resistance mutations (any amino acid change from wild-type for D30, G48, I50, V82 or L90) associated with protease inhibitors; and 32% had primary resistance mutations (K103N or Y181C) associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). HIV-1 reverse transcriptase mutations associated with nucleoside resistance were defined according to the Resistance Collaborative Group definition as one or more of the following: M41L, A62V, K65R, D67N, T69D/N, K70R, L74V/I, V75T, F77L, Y115F, F116Y, Q151M, M184V, L210W, T215Y/F or K219Q [8].

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Subject accountability

Three patients did not receive study drug. During the first 24 weeks of the study, more patients in the placebo group (25%) compared to those in the tenofovir DF groups (9–16%) discontinued study drug (Fig. 1). Through 48 weeks, 24–26% of patients in the three tenofovir DF-treated groups discontinued study drug.

Fig. 1
Fig. 1
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Plasma HIV-1 RNA response

Patients adding tenofovir DF once daily to a stable background antiretroviral regimen resulted in statistically significant mean decreases in the co-primary efficacy endpoints, the average change in HIV-1 RNA from week 0 to week 4 (DAVG4) and week 0 to week 24 (DAVG24) (Table 2). The DAVG4 was 0.02, −0.22 (P = 0.008), −0.44 (P < 0.001), and −0.62 (P < 0.001) for the placebo, tenofovir DF 75 mg, 150 mg, and 300 mg groups, respectively. These changes remained statistically significant with a DAVG24 of 0.02, −0.26 (P = 0.013), −0.34 (P = 0.002), and −0.58 (P < 0.001) in log10 copies/ml plasma HIV-1 RNA for the placebo, tenofovir DF 75 mg, 150 mg, and 300 mg groups, respectively. The antiviral response to tenofovir DF was durable and sustained with a DAVG48 of −0.33, −0.34 and −0.62 in log10 copies/ml plasma HIV-1 RNA for the tenofovir DF 75 mg, 150 mg and 300 mg groups, respectively.

Table 2
Table 2
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The incidence of modifications to background antiretroviral treatment was balanced among all four groups during the first 24 weeks on study (placebo, 32%; 75 mg, 27%; 150 mg, 27%; 300 mg, 31%). As a consequence, the significant antiviral responses seen through week 24 were unlikely to be influenced by changes in background ART. Through 48 weeks, the incidence of modifications in background ART remained balanced among the groups (75 mg 44%, 150 mg 47%, 300 mg 47%).

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HIV resistance data

Genotypic and phenotypic resistance testing was also performed, and is described fully in a separate paper [9].

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CD4 cell count response

Pairwise comparisons revealed no statistically significant differences between treatment groups in mean change in CD4 cell count at any pretreatment or on-treatment time point. By 24 weeks of treatment, mean changes in CD4 cell counts were +20 × 106 cells/l, +18 × 106 cells/l, 0 cells/l, and –14 × 106 cells/l in the placebo, 75 mg, 150 mg, and 300 mg groups, respectively. After 48 weeks of treatment, mean changes in CD4 counts were +10 × 106 cells/l, +20 × 106 cells/l and +11 × 106 cells/l in the tenofovir DF 75 mg, 150 mg, and 300 mg groups, respectively.

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Adverse event profile

In the first 24 weeks, headache, asthenia, pain, diarrhea, nausea, vomiting, pharyngitis, and rash were the most common clinical adverse events seen in this study, each occurring in > 20% of study patients. Of these, only diarrhea appeared to be more common in the tenofovir DF groups (21–25%) than in the placebo group (14%). By 48 weeks, additional events occurring in > 20% of patients were viral infection, abdominal pain, flu-like symptoms, back pain, rhinitis, and cough. No dose-related increase in the incidence of any adverse events was observed.

The incidences of grade 3 or 4 clinical adverse events were similar in all four groups and none of the comparisons between these groups through weeks 24 or 48 were statistically significant (all P-values > 0.05), as shown by the Wilcoxon rank sum test (Table 3). Apart from depression (6% in the 300 mg group), no grade 3 or 4 event occurred in more than 5% of patients in any group throughout the 48-week study period.

Table 3
Table 3
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Grade 3 or 4 laboratory abnormalities occurring in ≥ 10% of the patients during the first 24 weeks included elevated levels of creatine kinase (10% overall) and triglycerides (12% overall), but for both parameters the incidence in the tenofovir DF 300 mg group was less than that in the placebo group (Table 3). No additional grade 3 or higher laboratory abnormalities were seen through 48 weeks and there was no evidence of a dose effect for any of these parameters.

No clinically significant renal abnormalities were observed and no patient was discontinued from study because of serum creatinine elevations. The median serum creatinine values for the four original dose groups remained constant from 0.8 to approximately 0.9 mg/dl through 48 weeks on treatment. Two patients (75 mg group and placebo crossover to 300 mg group) developed a confirmed grade 1 (two consecutive values 0.5 mg/dl greater than the baseline value) serum creatinine elevation, but both resumed dosing with tenofovir DF and completed the 48-week study. During the 48-week study, no patient developed a grade 2 (2.1–3.0 mg/dl) or higher serum creatinine elevation.

No marked changes from baseline in median phosphorus levels occurred in any treatment group through week 24 or in the three tenofovir DF groups through week 48. The incidence of treatment emergent grade 2 hypophosphatemia (1.5–1.9 mg/dl) at 24 weeks was similar between the placebo (4%) and tenofovir DF groups (2%–7%). Notably, none of the placebo patients developed grade 1–4 hypophosphatemia after crossing over to tenofovir DF 300 mg for 24 weeks. The incidence of grade 2 hypophosphatemia at week 48 was similar to that at week 24. Through 48 weeks, no patient developed treatment emergent grade 3 or 4 hypophosphatemia.

The incidence of grade 2 proteinuria at 24 weeks was similar between the placebo (14%) and tenofovir DF groups (6%–7%). Through 48 weeks, no patient in any group experienced grade 3 or 4 proteinuria. Further, the incidence of graded urine protein abnormalities was similar across the active treatment groups, and there was no evidence of a dose effect.

Sixty-two patients at selected sites were monitored for bone mineral density using DXA. Baseline bone mineral density was similar among the four groups, with mean values ranging from 1.071 to 1.160 g/cm2. The median percentage changes from baseline at week 24 were −2.00%, −0.16%, −0.15%, and −1.19% for the placebo, tenofovir DF 75 mg, 150 mg, and 300 mg dose groups, respectively, and were within the range of measurement error and not statistically significant. At week 48, the median changes from baseline were +0.68%, −1.64%, and −1.35% for the 75 mg, 150 mg, and 300 mg dose groups, respectively, suggesting no dose effect.

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Discussion

In treatment-experienced patients with baseline nucleoside resistance mutations the addition of tenofovir DF to stable antiretroviral regimens resulted in significant reductions in the average change in plasma HIV-1 RNA from week 0 to weeks 4 and 24. Furthermore, these reductions were durable. Exhibiting a safety profile similar to placebo through 24 weeks, this study illustrates that tenofovir DF is both safe and well tolerated. No dose-related increase in the incidence of any adverse event was observed during this study. Furthermore, no significant changes in renal function were observed through 48 weeks.

There are few similar studies with patient populations as treatment-experienced as the GS-98-902 population. In the CNA3002 study, abacavir or placebo was added to background therapy in patients with HIV-1 RNA between 400 and 50 000 copies/ml [10]. Only 5% of patients had more than 18 months of prior ART while in GS-98-902 patients had a mean 55 months of prior ART. The addition of abacavir resulted in a median change from baseline in log10 copies/ml plasma HIV-1 RNA of −0.44 at week 16. The addition of tenofovir DF 300 mg resulted in a statistically significant average change from baseline to week 24 in log10 copies/ml HIV-1 RNA (DAVG24) of −0.58. In CNA3002 and GS-98-902, the change in median CD4 cell count from baseline did not differ significantly between the active and placebo arms. These results suggest that in treatment-experienced patients, the addition of a single antiretroviral agent to stable background therapy may result in only small changes in CD4 cell counts.

The next generation of antiretroviral agents will include efficacious and durable regimens that offer convenience, ensure tolerability, and preserve future treatment options. Based on the results from this clinical trial a regimen containing tenofovir DF has the potential to address each of these needs by offering a safe and convenient single tablet, once daily NtRTI that can be effective in patients with pre-existing NRTI resistance. Further, tenofovir DF may represent a long-term component of any antiretroviral regimen, with only rare emergence of drug resistance mutations [9], leading to long-term viral suppression.

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Acknowledgements

The authors acknowledge the contributions of all the investigators, study site personnel and patients who participated in this study. We also thank I. McGowan, A. McCullough, and J. Elder for their contributions to the study.

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References

1. Balzarini J, Holy A, Jindrich J. et al. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother 1993, 37: 332–338.

2. Robbins BL, Srinivas RV, Kim C, Bischofberger N, Fridland A. Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2-phosphonomethoxypropyl)adenine (PMPA), Bis(isopropyloxymethylcarbonyl) PMPA. Antimicrob Agents Chemother 1998, 42: 612–617.

3. Wainberg MA, Miller MD, Quan Y. et al. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther 1999, 4: 87–94.

4. Shirasaka T, Kavlick MF, Ueno T. et al. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc Natl Acad Sci USA 1995, 92: 2398–2402.

5. Bloor S, Kemp SD, Hertogs K. et al. Patterns of HIV drug resistance in routine clinical practice: a survey of almost 12,000 samples from the USA in 1999. Antivir Ther 2000, 5 (Suppl 3): 132.132.

6. Shaw J-P. In vitro stability of bis POC PMPA (GS 4331) in the biological fluids. Gilead Sciences Report. No. 97-Vit-1278-001. March 7, 1997.

7. Barditch-Crovo P, Deeks S, Collier A. et al. Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother 2001, 45: 2733–2739.

8. DeGruttola V, Dix L, D'Aquila R. et al. The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antivir Ther 2000, 5: 41–48.

9. Margot NA, Isaacson E, McGowan I. et al. Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. AIDS 2002, 16: 1227–1235.

10. Katlama K, Bonaventura C, Plettenberg A. et al. The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind trial, CNA3002 European Study Team. AIDS 2000, 14: 781–789.

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Appendix

In addition to the authors, the investigators of the Study 902 Team included: R. Anderson, S. Brown, C. Cohen, B. Gripshover, S. Jacobson, P. Keiser, C. Lahart, J. L. Lennox, D. Mildvan, J. Nadler, M. Saag, J. H. Sampson, T. Schacker, G. Skowron, M. A. Thompson, J. Zurlo.

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Antiviral Research
Protective effect of the acyclic nucleoside phosphonate tenofovir toward human T-cell leukemia/lymphotropic virus type 1 infection of human peripheral blood mononuclear cells in vitro
Balestrieri, E; Sciortino, MT; Mastino, A; Macchi, B
Antiviral Research, 68(3): 154-162.
10.1016/j.antiviral.2005.09.001
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Hiv Medicine
Evaluation of hypophosphataemia in tenofovir disoproxil fumarate (TDF)-exposed and TDF-unexposed HIV-infected out-patients receiving highly active antiretroviral therapy
Buchacz, K; Brooks, JT; Tong, T; Moorman, AC; Baker, RK; Holmberg, SD; Greenberg, A
Hiv Medicine, 7(7): 451-456.

Antiviral Therapy
Antiretroviral efficacy and virological profile of a zidovudine/lamivudine/tenofovir disoproxil fumarate combination therapy in antiretroviral-naive patients
Masquelier, B; Neau, D; Boucher, S; Lavignolle-Aurillac, V; Schrive, MH; Recordon-Pinson, P; Ragnaud, JM; Fleury, H
Antiviral Therapy, 11(6): 827-830.

Clinical Drug Investigation
Renal safety of tenofovir in HIV-infected children - A prospective, 96-week longitudinal study
Vigano, A; Zuccotti, GV; Martelli, L; Giacomet, V; Cafarelli, L; Borgonovo, S; Beretta, S; Rombola, G; Mora, S
Clinical Drug Investigation, 27(8): 573-581.

Clinical Infectious Diseases
Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: Three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus
Karras, A; Lafaurie, M; Furco, A; Bourgarit, A; Droz, D; Sereni, D; Legendre, C; Martinez, F; Molina, JM
Clinical Infectious Diseases, 36(8): 1070-1073.

AIDS
Amprenavir and didanosine are associated with declining kidney function among patients receiving tenofovir
Crane, HM; Kestenbaum, B; Harrington, RD; Kitahata, MM
AIDS, 21(): 1431-1439.

AIDS Reader
Proximal Tubular Dysfunction Associated With Tenofovir and Didanosine Causing Fanconi Syndrome and Diabetes Insipidus: A Report of 3 Cases
Irizarry-Alvarado, JM; Dwyer, JR; Brumble, LM; Alvarez, S; Mendez, JC
AIDS Reader, 19(3): 114-121.

Antiviral Research
Strand transfer inhibitors of HIV-1 integrase: Bringing IN new era of antiretroviral therapy
McColl, DJ; Chen, XW
Antiviral Research, 85(1): 101-118.
10.1016/j.antiviral.2009.11.004
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Pharmacotherapy
Tenofovir: A nucleotide analog for the management of human immunodeficiency virus infection
Antoniou, T; Park-Wyllie, LY; Tseng, AL
Pharmacotherapy, 23(1): 29-43.

AIDS Reviews
Strategies for overcoming resistance in HIV-1 infected patients receiving HAART
Clotet, B
AIDS Reviews, 6(3): 123-130.

Clinical Infectious Diseases
Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment
Gallant, JE; Parish, MA; Keruly, JC; Moore, RD
Clinical Infectious Diseases, 40(8): 1194-1198.

Clinical Infectious Diseases
Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: The role of lopinavir-ritonavir-didanosine
Rollot, F; Nazal, EM; Chauvelot-Moachon, L; Kelaidi, C; Daniel, N; Saba, M; Abad, S; Blanche, P
Clinical Infectious Diseases, 37(): E174-E176.

Journal of Biological Chemistry
Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations
Deval, J; White, KL; Miller, MD; Parkin, NT; Courcambeck, J; Halfon, P; Selmi, B; Boretto, J; Canard, B
Journal of Biological Chemistry, 279(1): 509-516.
10.1074/jbc.M308806200
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Clinical Pharmacokinetics
Tenofovir disoproxil fumarate - Clinical pharmacology and pharmacokinetics
Kearney, BP; Flaherty, JF; Shah, J
Clinical Pharmacokinetics, 43(9): 595-612.

Bioorganic & Medicinal Chemistry Letters
Stereoselective synthesis of 9-beta-D-arabianofuranosyl guanine and 2-amino-9-(beta-D-arabianofuranosyl)purine
Yu, XJ; Li, GX; Qi, XX; Deng, YQ
Bioorganic & Medicinal Chemistry Letters, 15(3): 683-685.
10.1016/j.bmcl.2004.11.029
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Journal of Medical Virology
Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir
Trotta, MP; Bonfigli, S; Ceccherini-Silberstein, F; Bellagamba, R; D'Arrigo, R; Soldani, F; Zaccarelli, M; Bellocchi, MC; Lorenzini, P; Marconi, P; Boumis, E; Forbici, F; Comandini, UV; Tozzi, V; Narciso, P; Perno, CF; Antinori, A
Journal of Medical Virology, 78(5): 535-541.
10.1002/jmv.20573
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Journal of Infectious Diseases
Toward a pharmacogenetic understanding of nucleotide and nucleoside analogue toxicity
Hulgan, T; Haas, DW
Journal of Infectious Diseases, 194(): 1471-1474.

Infection
Effectiveness of Antiretroviral Regimens Containing Abacavir with Tenofovir in Treatment-Experienced Patients: Predictors of Virological Response and Drug Resistance Evolution in a Multi-Cohort Study
Di Giambenedetto, S; Torti, C; Prosperi, M; Manca, N; Lapadula, G; Paraninfo, G; Ladisa, N; Zazzi, M; Trezzi, M; Cicconi, P; Corsi, P; Nasta, P; Cauda, R; De Luca, A
Infection, 37(5): 438-444.
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Antiviral Research
Evaluation of antiretrovirals in animal models of HIV infection
Van Rompay, KKA
Antiviral Research, 85(1): 159-175.
10.1016/j.antiviral.2009.07.008
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Clinical Therapeutics
Tenofovir disoproxil fumarate: A nucleotide reverse transcriptase inhibitor for the treatment of HIV infection
Fung, HB; Stone, EA; Piacenti, FJ
Clinical Therapeutics, 24(): 1515-1548.

Annals of Pharmacotherapy
Tenofovir disoproxil fumarate
Grim, SA; Romanelli, F
Annals of Pharmacotherapy, 37(6): 849-859.
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Clinical Microbiology Reviews
Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections
De Clercq, E
Clinical Microbiology Reviews, 16(4): 569-+.
10.1128/CMR.16.4.569-596.2003
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Antimicrobial Agents and Chemotherapy
Tenofovir resistance and resensitization
Wolf, K; Walter, H; Beerenwinkel, N; Keulen, W; Kaiser, R; Hoffmann, D; Lengauer, T; Selbig, J; Vandamme, AM; Korn, K; Schmidt, B
Antimicrobial Agents and Chemotherapy, 47(): 3478-3484.
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Clinica Chimica Acta
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Markowitz, GS; Perazella, MA
Clinica Chimica Acta, 351(): 31-47.
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Clinical Infectious Diseases
Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America
Gupta, SK; Eustace, JA; Winston, JA; Boydstun, II; Ahuja, TS; Rodriguez, RA; Tashima, KT; Roland, M; Franceschini, N; Palella, FJ; Lennox, JL; Klotman, PE; Nachman, SA; Hall, SD; Szczech, LA
Clinical Infectious Diseases, 40(): 1559-1585.

Therapie
Assessment of renal abnormalities in 107 HIV patients treated with tenofovir
Lochet, P; Peyriere, H; Le Moing, V; Blayac, JP; Hansel, S; Reynes, J
Therapie, 60(2): 175-181.

Clinical Infectious Diseases
HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy
Roling, J; Schmid, H; Fischereder, M; Draenert, R; Goebel, FD
Clinical Infectious Diseases, 42(): 1488-1495.

Future Virology
Role of tenofovir in the treatment of chronic HBV infection
van Bommel, F; Berg, T
Future Virology, 3(3): 207-220.
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AIDS Reviews
Risk Factors for Gastrointestinal Adverse Events in HIV Treated and Untreated Patients
Hill, A; Balkin, A
AIDS Reviews, 11(1): 30-38.

Antimicrobial Agents and Chemotherapy
Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children
Hazra, R; Balis, FM; Tullio, AN; DeCarlo, E; Worrell, CJ; Steinberg, SM; Flaherty, JF; Yale, K; Poblenz, M; Kearney, BP; Zhong, LJ; Coakley, DF; Blanche, S; Bresson, JL; Zuckerman, JA; Zeichner, SL
Antimicrobial Agents and Chemotherapy, 48(1): 124-129.
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AIDS Patient Care and Stds
HIV and hepatitis B: A review
Thomas, C; Nelson, M; Stebbing, J
AIDS Patient Care and Stds, 17(): 623-633.

Scandinavian Journal of Infectious Diseases
Severe metabolic acidosis and renal failure in an HIV-1 patient receiving tenofovir
Hansen, ABE; Mathiesen, S; Gerstoft, J
Scandinavian Journal of Infectious Diseases, 36(5): 389-392.
10.1080/00365540410027157
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Scandinavian Journal of Infectious Diseases
Tubulopathy consecutive to tenofovir-containing antiretroviral therapy in two patients infected with human immunodeficiency virus-1
Breton, G; Alexandre, M; Duval, X; Prie, D; Peytavin, G; Leport, C; Vilde, JL
Scandinavian Journal of Infectious Diseases, 36(): 527-528.
10.1080/00365540310016169
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Antiviral Therapy
Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy
Cote, HCF; Magil, AB; Harris, M; Scarth, BJ; Gadawski, I; Wang, N; Yu, E; Yip, B; Zalunardo, N; Werb, R; Hogg, R; Harrigan, PR; Montaner, JS
Antiviral Therapy, 11(1): 79-86.

Expert Opinion on Drug Safety
Tenofovir-induced kidney injury
Gitman, MD; Hirschwerk, D; Baskin, CH; Singhal, PC
Expert Opinion on Drug Safety, 6(2): 155-164.
10.1517/14740338.6.2.155
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Nephrology Dialysis Transplantation
Prevalence of chronic kidney disease in Chinese HIV-infected patients
Cheung, CY; Wong, KM; Lee, MP; Liu, YL; Kwok, H; Chung, R; Chau, KF; Li, CK; Li, CS
Nephrology Dialysis Transplantation, 22(): 3186-3190.
10.1093/ndt/gfm350
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Hiv Clinical Trials
The safety and efficacy of switching stavuldine to tenofovir DF in combination with lamivudine and efavirenz in HIV-1-infected patients: Three-year follow-up after switching therapy
Madruga, JVR; Cassetti, I; Suleiman, JMAH; Etzel, A; Zhong, L; Holmes, CB; Cheng, AK; Enejosa, J
Hiv Clinical Trials, 8(6): 381-390.
10.1310/hct0806-381
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Antiviral Therapy
Macroenzyme creatine kinase (CK) type 2 in HIV-infected patients is significantly associated with TDF and consists of ubiquitous mitochondrial CK
Schmid, H; Muhlbayer, D; Roling, J; Sternfeld, T; Julg, B; Schlattner, U; Nelson, PJ; Bogner, JR; Wallimann, T; Goebel, FD
Antiviral Therapy, 11(8): 1071-1080.

Future Virology
From adefovir to Atripla(TM) via tenofovir, Viread(TM) and Truvada(TM)
De Clercq, E
Future Virology, 1(6): 709-715.
10.2217/17460794.1.6.709
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AIDS
Improvement of dyslipidemia in patients switching from stavudine to tenofovir: preliminary results
Domingo, P; Labarga, P; Palacios, R; Guerrero, MF; Terron, JA; Elias, MJP; Santos, J; Camps, MIR; Llibre, JM; Moreno, S
AIDS, 18(): 1475-1478.
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Expert Opinion on Pharmacotherapy
Use of tenofovir disoproxil fumarate and emtricitabine combination in HIV-infected patients
Gazzard, BG
Expert Opinion on Pharmacotherapy, 7(6): 793-802.
10.1517/14656566.7.6.793
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Biochemical Pharmacology
Acyclic nucleoside phosphonates: Past, present and future - Bridging chemistry to HIV, HBV, HCV, HPV, adeno-, herpes-, and poxvirus infections: The phosphonate bridge
De Clercq, E
Biochemical Pharmacology, 73(7): 911-922.
10.1016/j.bcp.2006.09.014
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Clinical Infectious Diseases
Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy
Reid, A; Stoehr, W; Walker, AS; Williams, IG; Kityo, C; Hughes, P; Kambugu, A; Gilks, CF; Mugyenyi, P; Munderi, P; Hakim, J; Gibb, DM
Clinical Infectious Diseases, 46(8): 1271-1281.
10.1086/533468
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International Journal of Clinical Practice
Tenofovir: what have over 1 million years of patient experience taught us?
Pozniak, A
International Journal of Clinical Practice, 62(8): 1285-1293.
10.1111/j.1742-1241.2008.01817.x
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Drugs
Tenofovir disoproxil fumarate - A review of its use in the management of HIV infection
Lyseng-Williamson, KA; Reynolds, NA; Plosker, GL
Drugs, 65(3): 413-432.

Current Medicinal Chemistry
Treating chronic hepatitis B: Today and tomorrow
Borgia, G; Gentile, I
Current Medicinal Chemistry, 13(): 2839-2855.

AIDS Research and Human Retroviruses
Progressive Renal Tubular Dysfunction Associated with Long-Term Use of Tenofovir DF
Kinai, E; Hanabusa, H
AIDS Research and Human Retroviruses, 25(4): 387-394.
10.1089/aid.2008.0202
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Annals of Internal Medicine
Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection a randomized trial
Squires, K; Pozniak, AL; Pierone, G; Steinhart, CR; Berger, D; Bellos, NC; Becker, SL; Wulfsohn, M; Miller, MD; Toole, JJ; Coakley, DF; Cheng, A
Annals of Internal Medicine, 139(5): 313-320.

Current Pharmaceutical Design
Phosphonomethoxyalkyl analogs of nucleotides
Holy, A
Current Pharmaceutical Design, 9(): 2567-2592.

Enfermedades Infecciosas Y Microbiologia Clinica
Spanish GESIDA/Nacional AIDS plan recommendations for antiretroviral therapy in HIV-infected adults (October 2004)
Iribarren, JA; Labarga, P; Rubio, R; Berenguer, J; Miro, JM; Antela, A; Gonzalez, J; Moreno, S; Arrizabalaga, J; Chamorro, L; Clotet, B; Gatell, JM; Lopez-Aldeguer, J; Martinez, E; Polo, R; Tuset, M; Viciana, P; Santamaria, JM; Kindelan, JM; Ribera, E; Segura, F
Enfermedades Infecciosas Y Microbiologia Clinica, 22(): 564-642.

AIDS
Renal tubular toxicity associated with tenofovir assessed using urine-beta 2 microglobulin, percentage of tubular reabsorption of phosphate and alkaline phosphatase levels
Kinai, E; Hanabusa, H
AIDS, 19(): 2031-2033.

Hepatology
Anti-hepatitis B virus efficacy of tendovir disoproxil fumarate in HIV-infected patients
Benhamou, Y; Fleury, H; Trimoulet, P; Pellegrin, I; Urbinelli, R; Katlama, C; Rozenbaum, W; Le Teuff, G; Trylesinski, A; Piketty, C
Hepatology, 43(3): 548-555.
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Infectious Disease Clinics of North America
Approach to the treatment-experienced patient
Gallant, JE
Infectious Disease Clinics of North America, 21(1): 85-+.
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AIDS Patient Care and Stds
Renal Function in Patients with Preexisting Renal Disease Receiving Tenofovir-Containing Highly Active Antiretroviral Therapy in the HIV Outpatient Study
Young, B; Buchacz, K; Moorman, A; Wood, KC; Brooks, JT
AIDS Patient Care and Stds, 23(8): 589-592.
10.1089/apc.2008.0232
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International Journal of Std & AIDS
Hepatitis B infection in an HIV-positive man treated with tenofovir: a case of re-infection or reactivation?
Richardson, D; Lamba, H
International Journal of Std & AIDS, 15(3): 204-205.

AIDS Reader
Renal safety of tenofovir disoproxil fumarate
Sax, PE; Gallant, JE; Klotman, PE
AIDS Reader, 17(2): 90-+.

American Journal of Health-System Pharmacy
Tenofovir: A nucleotide analogue reverse-transcriptase inhibitor for treatment of HIV infection
DeChristoforo, R; Penzak, SR
American Journal of Health-System Pharmacy, 61(1): 86-98.

AIDS Reviews
K65R, TAMs and tenofovir
Miller, MD
AIDS Reviews, 6(1): 22-33.

Journal of Clinical Microbiology
Role of baseline human immunodeficiency virus genotype as a predictor of viral response to tenofovir in heavily pretreated patients
Barrios, A; de Mendoza, C; Martin-Carbonero, L; Ribera, E; Domingo, P; Galindo, MJ; Galvez, J; Estrada, V; Dalmau, D; Asensi, V; Soriano, V
Journal of Clinical Microbiology, 41(9): 4421-4423.
10.1128/JCM.41.9.4421-4423.2003
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Scandinavian Journal of Infectious Diseases
Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients
Lerbaek, A; Kristiansen, TB; Katzenstein, TL; Mathiesen, L; Gerstoft, J; Nielsen, C; Larsen, K; Nielsen, JO; Obel, N; Laursen, AL; Nielsen, SD
Scandinavian Journal of Infectious Diseases, 36(4): 280-286.
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Hiv Clinical Trials
Tenofovir-containing nucleoside/nucleotide-only antiretroviral maintenance therapy: Decision making and virological outcome
Buehlmann, M; Chave, JP; Flepp, M; Schiffer, V; Keiser, O; Furrer, H
Hiv Clinical Trials, 7(2): 48-54.

Nefrologia
Acute renal failure and proximal renal tubular dysfuntion in a patient with acquired immunodeficiency syndrome treated with tenofovir
de la Prada, FJ; Prados, AM; Tugores, A; Uriol, M; Saus, C; Morey, A
Nefrologia, 26(5): 626-630.

Hiv Clinical Trials
Randomized controlled trial of once-daily tenofovir, lamivudine, and Lopinavir/Ritonavir versus remaining on the same regimen in virologically suppressed HIV-Infected patients on their first PI-Containing HAART regimen
Loutfy, MR; Ackad, N; Antoniou, T; Baril, JG; Conway, B; de Wet, J; Trottier, B; Kovacs, CM; Thompson, W; Martel, AY; Trottier, S; Rouleau, D; Shafran, SD; Rachlis, A; Fraser, C; Smaill, F; Walmsley, SL; Tseng, AL; Sampalis, JS
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AIDS
Genetic basis of variation in tenofovir drug susceptibility in HIV-1
Murray, RJ; Lewis, FI; Miller, MD; Brown, AJL
AIDS, 22(): 1113-1123.

Hiv Medicine
Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations
Audsley, J; Arrifin, N; Yuen, LKW; Ayres, A; Crowe, SM; Bartholomeusz, A; Locarnini, SA; Mijch, A; Lewin, SR; Sasadeusz, J
Hiv Medicine, 10(4): 229-235.
10.1111/j.1468-1293.2008.00675.x
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Clinical Infectious Diseases
Tenofovir disoproxil fumarate
Gallant, JE; Deresinski, S
Clinical Infectious Diseases, 37(7): 944-950.

Kidney International
HAART-related nephropathies in HIV-infected patients
Daugas, E; Rougier, JP; Hill, G
Kidney International, 67(2): 393-403.

Antiviral Therapy
Challenges for the clinical development of new nucleoside reverse transcriptase inhibitors for HIV infection
Wainberg, MA; Sawyer, JPC; Montaner, JSG; Murphy, RL; Kuritzkes, DR; Raffi, F
Antiviral Therapy, 10(1): 13-28.

Hiv Medicine
Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy
Winston, A; Amin, J; Mallon, PWG; Marriott, D; Carr, A; Cooper, DA; Emery, S
Hiv Medicine, 7(2): 105-111.

Hiv Medicine
HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation
Boucher, S; Recordon-Pinson, P; Ragnaud, JM; Dupon, M; Fleury, H; Masquelier, B
Hiv Medicine, 7(5): 294-298.

AIDS
Antiretroviral activity of didanosine in patients with different clusters of reverse transcriptase mutations
Blanco, JL; Biglia, A; De Lazzari, E; Mallolas, J; Martinez, E; Pumarola, T; Larrousse, M; Milinkovic, A; Leon, A; Lonca, M; Laguno, M; Gatell, JM
AIDS, 20(): 1891-1892.

Antiviral Therapy
Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir
Barnas, D; Koontz, D; Bazmi, H; Bixby, C; Jemsek, J; Mellors, JW
Antiviral Therapy, 15(3): 437-441.
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Drugs
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Chapman, TM; McGavin, JK; Noble, S
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Seminars in Liver Disease
New treatment of chronic hepatitis B
Lok, ASF
Seminars in Liver Disease, 24(): 77-82.

International Journal of Antimicrobial Agents
Nephrolithiasis and hydronephrosis in an HIV-infected man receiving tenofovir
Cicconi, P; Bongiovanni, A; Melzi, S; Tordato, F; Monforte, AD; Bini, T
International Journal of Antimicrobial Agents, 24(3): 284-285.
10.1016/j.ijantimicag.2004.04.005
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Journal of Medical Virology
Efficacy and safety of tenofovir double-dose in treatment-experienced HIV-infected patients: The TENOPLUS study
Dominguez, S; Ghosn, J; Peytavin, G; Izzedine, H; Wirden, M; Ktorza, N; Miller, M; Aubron-Olivier, C; Trylesinski, A; Calvez, V; Deray, G; Katlama, C
Journal of Medical Virology, 79(2): 105-110.
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Expert Opinion on Pharmacotherapy
Evolving simplified treatment strategies for HIV infection: the role of a single-class quadruple-nucleoside/nucleotide regimen of trizivir and tenofovir
Mastroianni, CM; d'Ettorre, G; Vullo, V
Expert Opinion on Pharmacotherapy, 7(): 2233-2241.
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European Journal of Medical Research
Metabolic and anthropometric changes one year after switching from Didanosine/Stavudine to Tenofovir in HIV-infected patients
Claas, GJ; Julg, B; Roling, J; Goebel, FD; Bogner, JR
European Journal of Medical Research, 12(2): 54-60.

Hiv Medicine
Antiviral activity of low-dose alovudine in antiretroviral-experienced patients: results from a 4-week randomized, double-blind, placebo-controlled dose-ranging trial
Ghosn, J; Quinson, AM; Sabo, ND; Cotte, L; Piketty, C; Dorleacq, N; Bravo, ML; Mayers, D; Harmenberg, J; Mardh, G; Valdez, H; Katlama, C
Hiv Medicine, 8(3): 142-147.

Infection Control and Hospital Epidemiology
Assessment of adverse events associated with antiretroviral regimens for postexposure prophylaxis for occupational and nonoccupational exposures to prevent transmission of human immunodeficiency virus
Luque, A; Hulse, S; Wang, D; Shahzad, U; Tanzman, E; Antenozzi, S; Smith, B
Infection Control and Hospital Epidemiology, 28(6): 695-701.
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Antiviral Therapy
Comparison of the antiviral activity of adefovir and tenofovir on hepatitis B virus in HIV-HBV-coinfected patients
Lacombe, K; Gozlon, J; Boyd, A; Boelle, PY; Bonnard, P; Molina, JM; Miailhes, P; Lascoux-Combe, C; Serfaty, L; Zoulim, F; Girard, PM
Antiviral Therapy, 13(5): 705-713.

Revue De Medecine Interne
Antiretroviral therapy in human immunodeficiency virus infection: An update
Chaix, F; Goujard, C
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10.1016/j.revmed.2008.12.014
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Journal of Antimicrobial Chemotherapy
The use of tenofovir disoproxil fumarate for the treatment of nucleoside-resistant HIV-1
McColl, DJ; Miller, MD
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Annals of Pharmacotherapy
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Fulco, PP; Kirian, MA
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Journal of Infectious Diseases
Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: A randomized placebo-controlled trial
Molina, JM; Marcelin, AG; Pavie, J; Heripret, L; De Boever, CM; Troccaz, M; Leleu, G; Calvez, V
Journal of Infectious Diseases, 191(6): 840-847.

Nephrology Dialysis Transplantation
Long-term renal safety of tenofovir disoproxil fumurate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study
Izzedine, H; Hulot, JS; Vittecoq, D; Gallant, JE; Staszewski, S; Launay-Vacher, V; Cheng, A; Deray, G
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Antiviral Therapy
Impact of newly available drugs on clinical progression in patients with virological failure after exposure to three classes of antiretrovirals
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Antiviral Therapy, 10(4): 563-573.

International Journal of Std & AIDS
The cost of antiretroviral drugs and influence on prescribing policies
Jones, R; Gazzard, B
International Journal of Std & AIDS, 17(8): 499-506.

Antiviral Therapy
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Keywords:

Tenofovir DF; TDF; PMPA; HIV; AIDS; antiretroviral-experienced

© 2002 Lippincott Williams & Wilkins, Inc.

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