sign in sign up
<<
Home , Atazanavir, Emtricitabine

ls & vira An ti ti n re A t r f o o v l i

a r

a Journal of

n

l

r

s Dong et al., J Antivir Antiretrovir 2012, 4:1

u o

J DOI: 10.4172/jaa.1000038 ISSN: 1948-5964 Antivirals & Antiretrovirals

Research Article Article OpenOpen Access Access Safety and Effectiveness of Tenofovir/ or Plus Boosted in Treatment Experienced HIV Infected Adults at Two Urban Private Medical Practices Betty J. Dong1*, Douglas J. Ward2, Lisa A. Chamberlain3, Y. Sunila Reddy4, Ramin Ebrahimi4, John F. Flaherty4 and William F. Owen5 1University of California School of Pharmacy, San Francisco, CA 2Dupont Circle Physicians Group, Washington, DC 3Virginia Mason Medical Center, Seattle, Washington 4Gilead Sciences Inc., Foster City, CA 5Private Practice, San Francisco, CA

Abstract Objectives: The efficacy and safety of once daily ritonavir-boosted atazanavir (ATV/r) plus tenofovir (TDF) and emtricitabine (FTC) or lamivudine (3TC) was evaluated in the management of treatment experienced HIV-infected patients in routine clinical practice. Research design and methods: A retrospective analysis was performed in HIV infected patients residing at two active, urban clinical practices receiving at least one month of tenofovir, emtricitabine or lamviudine plus ritonavir boosted atazanavir following a change from another antiretroviral regimen to simplify or reduce . Parameters evaluated included the proportion of patients with HIV RNA <400 copies/mL; change in CD4 count from baseline (start of both TDF and ATV/r), adverse effects, and laboratory changes over time in estimated glomerular filtration rate (calculated creatinine clearance and MDRD) and lipids. Main outcome measures: One hundred sixty five patients, the majority being Caucasian and male, were studied. Twenty nine (18%) discontinued therapy, including 4 for adverse events and 5 for virologic failure. At baseline, 71% of patients had HIV RNA values <400 copies/mL. At 12 months, 81/90 (90%) patients remaining on therapy had HIV RNA <400 copies/mL, including 17/25 (68%) of those with baseline HIV RNA ≥400 copies/m; 88% (35/40) achieved HIV RNA <75 c/mL. Median increase in CD4 count at 12 months was 26 cells/uL. Grade 4 hyperbilirubinemia occurred in 12% of patients. Estimated glomerular filtration rates did not change significantly by either the Cockcroft-Gault or MDRD method. At 12 months, median declines from baseline in total cholesterol, LDL- cholesterol, HDL-cholesterol, and triglycerides were -14, -18, -1, and -12 mg/dL, respectively. Conclusions: In routine clinical practice, a once-daily regimen containing ATV/r plus TDF/FTC or 3TC controlled HIV in most patients without renal toxicity and improved the lipid profile.

Keywords: Antiretroviral therapy; Tenofovir; Ritonavir boosted Ritonavir boosted atazanavir (ATV) has been associated with less atazanavir; Treatment-experienced HIV infected patients; Renal adverse lipid effects when compared to other PIs such as ritonavir function; Lipids boosted [16-21]. Atazanavir typically is associated with indirect hyperbilirubinemia but infrequently causes scleral icterus and Introduction and rarely produces clinical hepatitis. This cosmetic effect is HIV infection can now be managed as a chronic disease due to often rapidly reversible upon its discontinuation Ritonavir boosting the availability of effective and tolerable antiretroviral therapy (ART) allows a lower daily dose (300 mg) of ATV to be effective; however, such that can be administered once daily to promote long term adherence an addition may produce additional adverse gastrointestinal effects and survival. However, drug , particularly metabolic and adverse consequences on serum lipids. Since TDF concentrations complications, such as dyslipidemia from protease inhibitors (PI), are increased by an unknown mechanism when co-administered with and renal toxicity from nucleoside inhibitors ATV, the potential for tenofovir-induced renal toxicity may be also be (NRTIs) such as tenofovir can be problematic [1-5]. The combination increased. of ritonavir boosted atazanavir (ATV/r) plus tenofovir (TDF) and emtricitabine (FTC) is recommended as initial ART by US and European HIV treatment guidelines and as an alternative regimen in *Corresponding author: Betty J. Dong, University of California School of Pharmacy, San Francisco, CA, E-mail: [email protected] the WHO guidelines [6-8]. Received December 20, 2011; Accepted January 05, 2012; Published January fumarate (TDF), a once-daily nucleotide 07, 2012 reverse transcriptase inhibitor, has proven immunologic and virologic Citation: Dong BJ, Ward DJ, Chamberlain LA, Reddy YS, Ebrahimi R, et al. efficacy when administered in combination with other antiretroviral (2012) Safety and Effectiveness of Tenofovir/Emtricitabine or Lamivudine Plus agents in both treatment naïve and treatment-experienced patients Ritonavir Boosted Atazanavir in Treatment Experienced HIV Infected Adults at [9-12]. In clinical trials, TDF has displayed a more favorable effect on Two Urban Private Medical Practices. J Antivir Antiretrovir 4: 001-005. doi:10.4172/ jaa.1000038 the lipid profile compared to thymidine analogs such as and [13]. TDF is renally excreted and discontinuations due Copyright: © 2012 Dong BJ, et al. This is an open-access article distributed under to renal-related adverse events have been reported with an estimated the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and incidence of 0.5-2% [14-16]. source are credited.

J Antivir Antiretrovir ISSN:1948-5964 JAA, an open access journal Volume 4(1): 001-005 (2012) - 001 Citation: Dong BJ, Ward DJ, Chamberlain LA, Reddy YS, Ebrahimi R, et al. (2012) Safety and Effectiveness of Tenofovir/Emtricitabine or Lamivudine Plus Ritonavir Boosted Atazanavir in Treatment Experienced HIV Infected Adults at Two Urban Private Medical Practices. J Antivir Antiretrovir 4: 001-005. doi:10.4172/jaa.1000038

Although data from controlled trials demonstrate virologic efficacy patients (21%) treated at the Washington, D.C. clinic site that received and safety, experiences in routine clinical practice may not always be ATV 400 mg/day without ritonavir boosting were also included. Data similar. Therefore, a retrospective study was undertaken to evaluate the were analyzed both for the overall population and separately for those virologic and immunologic efficacy as well as the safety and tolerability patients who did and did not receive ritonavir boosting. Patients of once daily regimens containing ATV/r and TDF in treatment- received antiretroviral therapy that included TDF and ATV/r (or ATV) experienced patients at two large, urban HIV clinical practices. for a median (interquartile range [IQR]) of 11 (9, 12) months. Sixty- Patients and Methods eight percent of these patients also received either FTC (38%) or 3TC (30%) with TDF + ATV/r therapy. The majority of patients (>90%) were Retrospective chart reviews were conducted from July 2003 to protease inhibitor (e.g. , ) and nucleoside reverse March 2005 on treatment experienced HIV-1 infected patients residing transcriptase experienced (e.g. , zidovudine, stavudine) while in two active, urban clinical practices (San Francisco, California and 29% were non-nucleoside reverse transcriptase inhibitor experienced. Washington, D.C.). Patients included were required to have received There were 29 patients (18%) who had their TDF and/or ATV at least one month of concomitant once daily TDF and ritonavir discontinued. This included one patient who expired while on therapy boosted ATV (ATV/r) following the change from other ART regimens. (determined not to be study drug-related), 4 patients that had TDF The major reason for this ART change was to reduce toxicities and/ and/or ATV discontinued for an adverse event (1 patient each ‑ scleral or simplify therapy. At one site (Washington, D.C.), a small cohort of icterus, , grade 3 serum creatinine elevation, and dizziness/ patients who received TDF with un-boosted-ATV (400 mg/day) were fatigue), 5 patients who had their therapy changed for virologic failure also included. This regimen was started before the pharmacokinetic (confirmed HIV RNA ≥ 400 copies/mL), 4 patients who were lost to drug interaction between TDF and ATV was identified. follow-up, 4 patients who switched to other agents, and 11 patients The chart review included demographic information, HIV-1 who discontinued for personal or other reasons. RNA plasma concentrations, CD4 cell counts, clinical laboratory tests Efficacy (including serum creatinine [SCr], total , fasting lipids [total cholesterol, LDL cholesterol (LDL-c), HDL-cholesterol (HDL-c), At baseline, 117 patients (71%) had HIV RNA values <400 copies/ triglycerides), prior and current ART, concurrent medications, and ml; of which 55 had HIV RNA <75 copies/mL; 44 patients (27%) clinical adverse events as reported in the patient’s medical record. This had HIV RNA ≥400 c/mL, and 4 patients (2%) had missing values at research was approved by the University of California Committee on baseline. At the 12 month assessment, 90% of patients with available Human Research and a private Institutional Review Board in Wash HIV RNA values (81/90 patients, including 9/25 on unboosted ATV) DC. had < 400 copies/mL; 88% (35/40) had HIV RNA <75 c/mL. Sixty- three of the 64 patients (98%) with HIV RNA <400 c/mL at baseline Data were collected for visits at baseline (defined as the first maintained suppression through 12 months, and 17 of 25 visit at which both TDF and ATV or ATV/r were being prescribed patients (68.0%) with baseline HIV RNA ≥400 c/mL achieved HIV concurrently), and during clinic visit windows centered on 2-4, 5-7, RNA <400 c/mL following treatment with TDF+ ATV/r (Figure 1). 9-10, and 11-13 months after baseline. Data from both sites were Of the 55 patients with HIV RNA <75 c/mL at baseline, using the last pooled for analysis. The primary effectiveness endpoint was the observation or through 12 months, 51 patients maintained HIV RNA proportion of patients with HIV RNA <400 c/mL (most sensitive assay <75 c/mL; 13 patients with detectable viral load at baseline achieved available at that time at the WASH DC site). HIV RNA <75 c/mL was HIV-RNA <75 c/mL at 12 months. collected at the San Francisco site. The change in CD4 cell count from baseline, graded laboratory values, change from baseline in fasting A slightly higher proportion of patients receiving ATV/r (75%) than lipid profile, and estimations of glomerular filtration rate (calculated receiving unboosted ATV (65%) had HIV RNA <400 c/mL at baseline. creatinine clearance by the Cockroft Gault (C-G) method, and by the abbreviated Modified Diet in Renal Disease [MDRD] method) were Boosteda Unboostedb Overall also determined. Clinical adverse events were captured where available. Characteristic n = 131 n = 34 n = 165 Age (mean SD) 47 ± 9.6 44 ± 6.4 46 ± 9.1 Statistical analysis Gender Male, n (%) 129 (98.5%) 34 (100%) 163 (98.8%) The safety population included all subjects who received at least Female, n (%) 2 (1.5%) 0 (0%) 2 (1.2%) one dose of TDF with ATV, the efficacy population consisted of all Race patents remaining on therapy (as treated). Patients receiving lipid Asian, n (%) n/a n/a 5 (3.0%) lowering agents at baseline and those initiated during the study were Black, n (%) n/a n/a 12 (7.3%) not censored during data analyses. The Wilcoxon sign rank test was Hispanic, n (%) n/a n/a 3 (1.8%) White, n (%) n/a n/a 145 (87.9%) used to test the significance of changes from baseline. Descriptive Treatment duration in statistics were used to summarize patient demographic data, baseline monthsc, median 11 (1–17) 19 (6–33) 11 (1­33) characteristics, and change from baseline for each of the endpoints. (range) Footnote: aall values in mg/dL Results a300 mg atazanavir boosted with 100 mg ritonavir b400 mg atazanavir given without ritonavir A total of 165 treatment-experienced patients were included in cData available for 99 patients the final analysis; 88 patients from the Washington, D.C., site and 77 SD, standard deviation from the San Francisco site. Nearly all study patients were male and n/a, not available Caucasian, with mean age of 46±9.1 (SD) years (Table 1). A cohort of 39 Table 1: Demographics.

J Antivir Antiretrovir ISSN:1948-5964 JAA, an open access journal Volume 4(1): 001-005 (2012) - 002 Citation: Dong BJ, Ward DJ, Chamberlain LA, Reddy YS, Ebrahimi R, et al. (2012) Safety and Effectiveness of Tenofovir/Emtricitabine or Lamivudine Plus Ritonavir Boosted Atazanavir in Treatment Experienced HIV Infected Adults at Two Urban Private Medical Practices. J Antivir Antiretrovir 4: 001-005. doi:10.4172/jaa.1000038

Patients in both groups had a positive response to treatment with TDF/ 140 FTC or 3TC + ATV/r: at 12 months, 94% and 75% of patients receiving ATV/r and unboosted ATV, respectively, had HIV RNA <400 c/mL at 120 12 months.

CD4 counts remained essentially unchanged from baseline. At 100 96.2 baseline, the median (interquartile range [IQR]) CD4 count was 475 91.5 (317, 660), which was similar in patients receiving boosted compared 80 to unboosted ATV. Overall, the median (IQR) change from baseline at 77.0 76.6 6 months (n = 128) and 12 months (n = 89) were 26 (‑54, 103) and 26 (‑46, 107) cells/mm3, respectively. Similar changes were observed for 60 boosted versus unboosted ATV containing regimens. Adverse events 40 Glomerular Filtration Rate

During the study period, 20 patients (12%) experienced Grade 4 MDRD 20 hyperbilirubinemia, 69 (42%) Grade 3, and 40 (30%) Grade 2. A higher C-G proportion of patients receiving boosted ATV (46%, n = 60) than unboosted (27%, n = 9) had Grade 3 hyperbilirubinemia; 3 patients on 0 0136912 unboosted ATV had Grade 4. One patient with scleral icterus, who also had Grade 3 hyperbilirubinemia, discontinued the study. Study Month Renal assessment: Median (IQR) estimated glomerular filtration n = 161 128 131 134 106 88 rate (eGFR) as determined by the C-G and MDRD methods through Figure 2: Median [IQR] estimated glomerular filtration rate based on the Cock- roft Gault formula (mL/min) and the abbreviated Modified Diet in Renal Disease 12 months are presented in Figure 2. At baseline, median (IQR) eGFR (mL/min/1.73 m2) method through 12 months. The number of patients at each was 96 (82, 114) mL/min by C-G and 77 (68, 97) mL/min/1.73m2 by time point is indicated at the bottom. MDRD. The median change in eGFR from baseline at 12 months (n =

88) was 0 (-11 to 11) mL/min by C-G and 0 (-11 to 11) mL/min/1.73 Baseline Change from Baseline at 12 Months m2 by MDRD. Neither measure changed significantly over the 12 a months of the study. Confirmed creatinine increases from baseline Parameters N Median (IQR) N Median (IQR) p-value were observed in 6 patients (3 with Grade 1, 2 with Grade 2, and 1 with Total cholesterol 163 182 (154 to 215) 85 –14 (–38 to 15) p = 0.02 Grade 3 events). Treatment (TDF + + 3TC + ATV/r) was discontinued in one patient, with history of right renal atrophy and LDL Cholesterol 126 100.5 (80 to 123) 65 –8 (–25 to 13) p=0.10 nephrolithiasis, who experienced a Grade 3 Scr increase from 1.5 mg/ dL at baseline to 3.2 mg/dL. The last available Scr for this patient after HDL Cholesterol 151 42 (33 to 48) 79 –1 (–5 to 4) p=0.54 TDF discontinuation was 1.7 mg/dL. Another patient with a history Triglycerides 159 190 (121 to 309) 85 –12 (–96 to 41) p=0.08

Footnote: aall values in mg/dL IQR = interquartile range LDL= low density lipoprotein 100 HDL = high density lipoprotein Table 2: Changes from baseline in fasting lipid concentrations.

80 of nephrolithiasis continued TDF + ATV/r without any negative renal consequences; his last serum creatinine was 0.93 mg/dL. 60 ent c Lipid assessments: Fasting lipid profiles are presented in Table Pe r 2. At the 12 month treatment window, reductions in median total 40 cholesterol (p=0.02), HDL-c, LDL-c, and triglycerides were observed. Median LDL-c and total cholesterol were at the optimal (LDL-c <100 20 Baseline <400 c/mL mg/dL) and desirable range (total cholesterol <200mg/dL) as defined by Baseline >/=400 c/mL Overall the National Cholesterol Education Program, Adult Treatment Panel 0 III at baseline and remained there 12 months after study initiation 0 1 3 6 9 12 [22]. Lipid lowering agents were used by 45 of 77 patients at the San Visit (month) Francisco site; these agents were used prior to study initiation in all n (<400 c/mL) 117 95 94 96 79 6 4 patients and continued at the same dose level throughout the period n (>/=400 c/mL) 44 37 34 34 23 2 5 n (total) 161 132 128 130 102 89 of evaluation. This data was not available for the Washington DC site. Figure 1: Proportion of patients with HIV RNA <400 copies/mL. Separate plots Discussion are provided for the overall population at each time point, and for those with baseline HIV RNA values <400 c/mL or ≥400 c/mL. The number of patients in In this retrospective study of treatment-experienced patients in the each group at each time point is presented at the bottom. real world community setting, >90% of patients achieved or maintained

J Antivir Antiretrovir ISSN:1948-5964 JAA, an open access journal Volume 4(1): 001-005 (2012) - 003 Citation: Dong BJ, Ward DJ, Chamberlain LA, Reddy YS, Ebrahimi R, et al. (2012) Safety and Effectiveness of Tenofovir/Emtricitabine or Lamivudine Plus Ritonavir Boosted Atazanavir in Treatment Experienced HIV Infected Adults at Two Urban Private Medical Practices. J Antivir Antiretrovir 4: 001-005. doi:10.4172/jaa.1000038

HIV RNA <400 c/mL after changing to at least 12 months of once daily In addition, the design precluded an assessment of adherence to once treatment that included mostly ritonavir boosted ATV and TDF. Two- daily therapy. Nonetheless, our results are noteworthy as they represent thirds of patients were also receiving either FTC or 3TC as their NRTI first-hand community experience on the efficacy, tolerability, and backbone. For the primary endpoint, a threshold of HIV-1 RNA <400 toxicity of these agents and, despite the limited design, are consistent copies/mL was chosen since at the time of study, an ultrasensitive HIV- with those reported in other prospective, controlled studies [30,31]. 1RNA assay was not available for all patients. However, the ultrasensitive In conclusion, the combined use of ATV plus TDF in combination assay was available in 47% (n=55) of subjects, mostly located at the SF with FTC or 3TC in two large urban clinical practices was safe, well site. Our results generated from a clinical practice community setting tolerated, and maintained virologic control of HIV in treatment- are very consistent with those reported in a prospective, open-label, experienced patients. Changing to an ATV/r plus TDF/FTC or randomized trial, in which 84% of treatment-experienced patients had 3TC containing regimen also resulted in a favorable effect on lipid HIV RNA <400 c/mL after 96 weeks of treatment with ATV/r and TDF parameters while eGFR remained stable. in an as-treated analysis [23]. In contrast, a prospective study of TDF + ATV/r found little improvement in viral load in patients with extensive Acknowledgement prior ART therapy due to presence of mutations at baseline showing This study was supported by an unrestricted educational grant from Gilead genotypic and phenotypic resistance to ATV/r [24]. Sciences, Foster City. References Administration of TDF with ATV results in a bi-directional pharmacokinetic drug interaction that results in an approximately 1. Rodriguez-Novoa S, Alvarez E, Labarga P, Soriano V (2010) Renal toxicity associated with tenofovir use. Expert Opin Drug Saf 9: 545-559. 25% increase in tenofovir serum concentrations while reducing ATV trough concentrations by as much as 40% [25]. This reduction in ATV 2. Woodward CL, Hall AM, Williams IG, Madge S, Copas A, et al. (2009) Tenofovir- serum concentrations by TDF is overcome by boosting ATV with low associated renal and bone toxicity. HIV Med 10: 482-487. dose (100 mg once daily) ritonavir [26]. Although the combination of 3. Szczech LA (2008) Renal dysfunction and tenofovir toxicity in HIV-infected unboosted ATV and TDF is not recommended, 9/25 of our patients patients. Top HIV Med 16: 122-126. achieved viral load suppression consistent with previous reports 4. Stein JH (2003) Dyslipidemia in the era of HIV protease inhibitors. Prog [27,28]. Cardiovasc Dis 45: 293-304. 5. Kapoor JR (2009) Management of dyslipidemia associated with protease Adverse events observed in our subjects are similar to other reports. inhibitors. Am J Cardiol 103: 292-293. As expected, ATV induced hyperbilirubinemia was common, but was 6. Department of Health and Human Services Panel (2011) Guidelines for use of not usually bothersome enough to warrant treatment discontinuation Antiretroviral Therapy in HIV-1-Infected Adults and Adolescents. [19,23,29]. Grade 3 hyperbilirubinemia was more common in patients receiving boosted than unboosted ATV but Grade 4 elevations were 7. World Health Organization (2010) Antiretroviral therapy for HIV infection in adults and adolescents. uncommon. Grade 3 to 4 laboratory abnormalities were reported in 59% of those receiving ritonavir boosted ATV compared to 20% on 8. European guidelines for HIV infection. unboosted ATV [30]. A single-arm 48-week study assessing safety 9. Squires K, Pozniak AL, Pierone G Jr, Steinhart CR, Berger D, et al. (2003) and efficacy of TDF/FTC with ATV/r in antiretroviral naïve patients Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial. Ann Intern Med 139: 313-320. observed Grade 3 elevations in 44% of patients and Grade 4 elevations occurred in 5% of patients [31]. 10. Schooley RT, Ruane P, Myers RA, Beall G, Lampiris H, et al. (2002) Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, Routine serum creatinine was regularly monitored in this cohort. double-blind study. AIDS 16: 1257-1263. One patient discontinued ART with a Grade 1 elevation in SCr which 11. Cassetti I, Madruga JV, Suleiman JM, Etzel A, Zhong L, et al. (2007) The safety continued to increase after discontinuation of TDF. However, no and efficacy of tenofovir DF in combination with lamivudine and significant deterioration of renal function was observed during the 12 through 6 years in antiretroviral-naive HIV-1-infected patients. HIV Clin Trials 8: 164-172. months using eGFR calculated by C-G and MDRD, a more accurate assessment of renal function. These findings are similar to several 12. Madruga JR, Cassetti I, Suleiman JM, Etzel A, Zhong L, et al. (2007) The safety and efficacy of switching stavudine to tenofovir df in combination with other prospective, controlled studies showing minimal reductions lamivudine and efavirenz in -1-infected patients: three-year follow-up after in GFR and less than a 2% incidence of serum creatinine elevations switching therapy. HIV Clin Trials 8: 381-390. [10,13-16,21,31]. Our findings suggest that TDF given with ATV is 13. Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM et al. (2004) well tolerated from a renal perspective with few patients experiencing Efficacy and safety of tenofovir DF vs stavudine in combination therapy in moderate to severe renal events. antiretroviral-naive patients: a 3-year randomized trial. JAMA 292:191-201. Both ATV and TDF have been reported to have favorable lipid 14. Gerard L, Chazallon C, Taburet AM, Girard PM, Aboulker JP, et al. (2007) Renal function in antiretroviral-experienced patients treated with tenofovir profiles when compared other antiretroviral classes, especially TDF disoproxil fumarate associated with atazanavir/ritonavir. Antivir Ther 12: 31-39. plus LPV/r [16,17,23,29,32]. In this study even with the inclusion of ritonavir, median fasting total cholesterol, LDL-c, and trigylcerides 15. Padilla S, Gutierrez F, Masia M, Canovas V, Orozco C (2005) Low frequency of renal function impairment during one-year of therapy with tenofovir-containing improved with the therapy change to TDF + ATV/r. A slight reduction regimens in the real-world: a case-control study. AIDS Patient Care STDS 19: in HDL-c was seen which is not likely to be of clinical relevance. 421-424. The primary limitation of this study is the non-comparative, 16. Vrouenraets S, Wit F, Fernandez Garcia E, Moyle G, Jackson A, et al. (2011) Randomized comparison of metabolic and renal effects of saquinavir/r or retrospective design. In addition, the somewhat heterogenous atazanavir/r plus tenofovir/emtricitabine in treatment-naive HIV-1-infected population consisted of mostly young men with minimal co-morbidities. patients. HIV Med 12: 620-631.

J Antivir Antiretrovir ISSN:1948-5964 JAA, an open access journal Volume 4(1): 001-005 (2012) - 004 Citation: Dong BJ, Ward DJ, Chamberlain LA, Reddy YS, Ebrahimi R, et al. (2012) Safety and Effectiveness of Tenofovir/Emtricitabine or Lamivudine Plus Ritonavir Boosted Atazanavir in Treatment Experienced HIV Infected Adults at Two Urban Private Medical Practices. J Antivir Antiretrovir 4: 001-005. doi:10.4172/jaa.1000038

17. Jemsek JG, Arathoon E, Arlotti M, Perez C, Sosa N, et al. (2006) Body fat human immunodeficiency virus-infected patients. Antimicrob Agents and other metabolic effects of atazanavir and efavirenz, each administered Chemother 48: 2091-2096. in combination with zidovudine plus lamivudine, in antiretroviral-naive HIV- infected patients. Clin Infect Dis 42: 273-280. 26. Le Tiec C, Barrail A, Goujard C, Taburet AM (2005) Clinical and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet 44: 18. Lu CL, Lin YH, Wong WW, Lin HH, Ho MW, et al. (2011) Outcomes of switch 1035-1050 to atazanavir-containing combination antiretroviral therapy in HIV-1-infected patients with hyperlipidemia. J Microbiol Immunol Infect 44: 258-264. 27. Giuntini R, Martinelli C, Ricci E, Vichi F, Gianelli E, et al. (2010) Efficacy and safety of boosted and unboosted atazanavir-containing antiretroviral regimens 19. Tremblay C, Trottier B, Rachlis A, Baril JG, Loutfy M, et al. (2011) Treatment in real life: results from a multicentre cohort study. HIV Medicine 11: 40-45. durability, effectiveness, and safety with atazanavir/ritonavir-based HAART regimen in treatment-naive HIV-infected patients. HIV Clin Trials 12: 151-160. 28. Pavie J, Porcher R, Torti C, Medrano J, Castagna A, et al. (2011) Efficacy and safety of a switch to unboosted atazanavir in combination with nucleoside 20. Podzamczer D, Andrade-Villanueva J, Clotet B, Taylor S, Rockstroh JK, et al. analogues in HIV-1-infected patients with virological suppression under (2011) Lipid profiles for vs. atazanavir/ritonavir, both combined with antiretroviral therapy. J Antimicrob Chemother 66: 2372-2378. tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment- naive HIV-1-infected patients (the ARTEN study). HIV Med 12: 374-382. 29. Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, et al. (2008) Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, 21. Daar ES, Tierney C, Fischl MA, Sax PE, Mollan K, et al. (2011) Atazanavir plus each in combination with tenofovir and emtricitabine, for management of ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results Ann Intern Med 154: 445-456. of the CASTLE study. Lancet 372: 646-655.

22. Brown DJ (2004) New guidelines for low-density lipoprotein levels from the 30. Malan DR, Kranz E, David N, Wirtz V, Hammond J, et al. (2008) Efficacy and National Cholesterol Education Program (NCEP): a 2004 update. Prog safety of atazanavir, with or without ritonavir, as part of once-daily highly active Cardiovasc Nurs 19: 165. antiretroviral therapy regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr 47: 161-167. 23. Johnson M, Grinsztejn B, Rodriguez C, Coco J, DeJesus E, et al. (2006) 96- week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ 31. Elion R, Cohen C, Ward D, Ruane P, Ortiz R, et al. (2008) Evaluation of efficacy, ritonavir in patients with multiple virologic failures. AIDS 20: 711-718. safety, pharmacokinetics, and adherence in HIV-1-infected, antiretroviral-naive patients treated with ritonavir-boosted atazanavir plus fixed-dose tenofovir DF/ 24. Piketty C, Gerard L, Chazallon C, Marcelin AG, Clavel F, et al. (2006) Salvage emtricitabine given once daily. HIV Clin Trials 9: 213-224. therapy with atazanavir/ritonavir combined to tenofovir in HIV-infected patients with multiple treatment failures: randomized ANRS 107 trial. Antivir Ther 11: 32. Soriano V, Garcia-Gasco P, Vispo E, Ruiz-Sancho A, Blanco F, et al. (2008) 213-221. Efficacy and safety of replacing lopinavir with atazanavir in HIV-infected patients with undetectable plasma viraemia: final results of the SLOAT trial. J 25. Taburet AM, Chazallon C, Vincent I, Gérard L, Calvez V, et al. (2004) Antimicrob Chemother 61: 200-205. Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated

J Antivir Antiretrovir ISSN:1948-5964 JAA, an open access journal Volume 4(1): 001-005 (2012) - 005