HIV Highlights From Seattle   CCO Independent Conference Coverage   of the 2012 Conference on Retroviruses and Opportunist...
HIV Highlights From Seattleclinicaloptions.com/hiv About These Slides  Users are encouraged to use these slides in their ...
HIV Highlights From Seattleclinicaloptions.com/hiv Faculty Joseph J. Eron, Jr., MD               Kimberly Y. Smith, MD, MP...
HIV Highlights From Seattleclinicaloptions.com/hiv Faculty Disclosures Joseph J. Eron, Jr., MD, has disclosed that he has ...
Please review the slide notes for a complete discussion of each    study by expert faculty  Joseph J. Eron, Jr., MD, and  ...
New Agents
HIV Highlights From Seattleclinicaloptions.com/hiv Elvitegravir/Cobicistat/TDF/FTC vs EFV/TDF/FTC in Treatment-Naive Patie...
HIV Highlights From Seattleclinicaloptions.com/hiv Elvitegravir/Cobicistat Regimen Noninferior to EFV Regimen at Wk 48    ...
HIV Highlights From Seattleclinicaloptions.com/hiv Safety of Elvitegravir/Cobicistat Regimen vs EFV Regimen  Significantl...
HIV Highlights From Seattle  clinicaloptions.com/hiv   Elvitegravir/Cobicistat/TDF/FTC vs   ATV/RTV + TDF/FTC in Tx-Naive ...
HIV Highlights From Seattleclinicaloptions.com/hiv Elvitegravir/Cobicistat Regimen Noninferior to ATV/RTV Regimen at Wk 48...
HIV Highlights From Seattleclinicaloptions.com/hiv Safety of Elvitegravir/Cobicistat Regimen vs ATV/RTV Regimen  Similar ...
HIV Highlights From Seattleclinicaloptions.com/hiv SPRING-1: Phase IIb Trial of Dolutegravir vs Efavirenz in Tx-Naive Pati...
HIV Highlights From Seattle clinicaloptions.com/hiv  GS-7340: Antiviral Activity of Novel  Prodrug of Tenofovir      Lowe...
HIV Highlights From Seattleclinicaloptions.com/hiv Greater Antiviral Activity of GS-7340 25 mg and 40 mg vs TDF           ...
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HIV Highlights From Seattle

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Join expert faculty members Joseph J. Eron, Jr., MD, and Kimberly Y. Smith, MD, MPH, for a review of the HIV highlights of this important annual conference.

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  • Please view the PowerPoint notes to review the faculty commentary on each slide.
  • Please review the slide notes for a complete discussion of each study by expert faculty Joseph J. Eron, Jr., MD, and Kimberly Y. Smith, MD, MPH
  • CLcr, creatinine clearance; EFV, efavirenz; FTC, emtricitabine; QD, once daily; TDF, tenofovir.   Kimberly Y. Smith, MD, MPH: This randomized trial compared the once-daily, single-tablet coformulation of elvitegravir/cobicistat/tenofovir/emtricitabine with fixed-dose efavirenz/tenofovir/emtricitabine in treatment-naive patients with HIV-1 RNA levels ≥ 5000 copies/mL. Mean CD4+ cell counts at baseline were 382-391 cells/mm3 and only 12% to 14% of patients had CD4+ cell counts ≤ 200 cells/mm3.   Joseph J. Eron, Jr., MD: Another important feature of the population enrolled in this study is that it was predominantly male, with women constituting only 10% to 12% of each treatment arm. In addition, study participants were required to have a creatinine clearance rate ≥ 70 mL/min, which is higher than other large, comparative studies and is in part because cobicistat has an effect on creatinine secretion. Creatinine levels increase modestly in most patients who initiate cobicistat, not because of impaired glomerular filtration, but rather because of reduced proximal tubular creatinine secretion. [1,2]   References 1. German P, Liu C, Warren D, et al. Effect of cobicistat on glomerular filtration rate (GFR) in subjects with normal and impaired renal function. Program and abstracts of the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2011; Chicago, Illinois. Abstract H2-804. 2. Lepist EI, Murray BP, Tong L, Roy A, Bannister R, Ray AS. Effect of cobicistat and ritonavir on proximal renal tubular cell uptake and efflux transporters. Program and abstracts of the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2011; Chicago, Illinois. Abstract A1-1724.
  • COBI, cobicistat; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; TDF, tenofovir. Kimberly Y. Smith, MD, MPH: Similar rates of HIV-1 RNA < 50 copies/mL at Week 48 were observed with elvitegravir/cobicistat/tenofovir/emtricitabine vs fixed-dose efavirenz/tenofovir/emtricitabine. An important finding is that although the efficacy rate was slightly lower among patients with baseline HIV-1 RNA > 100,000 copies/mL vs patients with baseline HIV-1 RNA ≤ 100,000 copies/mL in the elvitegravir/cobicistat/tenofovir/emtricitabine arm, the difference was not clinically relevant. However, another key point regarding efficacy in patient subgroups is the impact of baseline CD4+ cell count. In the elvitegravir/cobicistat/tenofovir/emtricitabine arm, 83% of patients with baseline CD4+ cell counts ≤ 350 cells/mm3 achieved HIV-1 RNA < 50 copies/mL at Week 48 vs 91% of patients with baseline CD4+ cell counts > 350 cells/mm3. However, it is useful to reiterate that the proportion of patients with baseline CD4+ cell counts ≤ 200 cells/mm3 was low, and therefore, we still have only limited information regarding the efficacy of this regimen among patients with lower CD4+ cell counts and high HIV-1 RNA at baseline.   Joseph J. Eron, Jr., MD: I agree with that assessment. Another notable result from this study is that primary resistance to the anchor drug, the integrase inhibitor elvitegravir or the NNRTI efavirenz, emerged in nearly the same number of patients: 7 and 8, respectively. Therefore, although both of these drugs are generally considered to have a low genetic barrier to resistance, only 2% of the total population developed either an integrase inhibitor resistance mutation on elvitegravir or an NNRTI resistance mutation on efavirenz. One difference between the 2 regimens was that if a patient developed resistance on the elvitegravir arm, they were likely to also develop NRTI resistance, whereas NRTI resistance on the efavirenz arm was somewhat less likely. I think that is a potential difference between the 2 treatment regimens, although it is a relatively modest difference given that approximately 350 patients received the drugs in either arm.
  • COBI, cobicistat; EFV, efavirenz; EVG, elvitegravir; HDL, high-density lipoprotein; LDL, low-density lipoprotein.   Joseph J. Eron, Jr., MD: In terms of safety, nausea occurred more frequently with elvitegravir/cobicistat/tenofovir/emtricitabine vs efavirenz/tenofovir/emtricitabine. It is interesting to note that most of the nausea was grade 1; it will be important to determine if that level of nausea will be bothersome to patients in clinical practice. The efavirenz-associated adverse effects were similar to previous trials, and only 4% to 5% of patients had to discontinue either treatment regimen as a result of toxicity. However, 4 patients discontinued the elvitegravir/cobicistat regimen because of renal dysfunction. One of the patients had a modest increase in creatinine. The other 3 patients had changes in renal function consistent with a tenofovir effect.   Kimberly Y. Smith, MD, MPH: A clinical point that might be useful for physicians is that the change in creatinine occurred early, within approximately the first 2 weeks, and was not progressive. Physicians who have extensive experience administering tenofovir know that there tends to be a progressive, stepwise increase in creatinine levels that does not plateau. Clinicians will be looking for ways to distinguish between elvitegravir/cobicistat and tenofovir toxicity, and the pattern of change in creatinine might be one difference, as well as the tell‑tale signs of tenofovir toxicity, including glucose in the urine, protein in the urine, and so on. Any clues that can be obtained from this study to assist with determining the source of changes in creatinine levels when they occur will be valuable.   Joseph J. Eron, Jr., MD: Finally, an unanticipated outcome of this study was that the cobicistat-containing regimen did not seem to have a strong effect on triglyceride levels. I expected that cobicistat might result in elevated triglyceride levels, similar to ritonavir, but this was not the case.   Kimberly Y. Smith, MD, MPH: I agree that the lipid effect of cobicistat appears to be more distinct from ritonavir than expected.
  • ATV, atazanavir; CLcr, creatinine clearance; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; QD, once daily; RTV, ritonavir; TDF, tenofovir; tx, treatment.   Kimberly Y. Smith, MD, MPH: The next study used a similar study design to compare elvitegravir/cobicistat/tenofovir/emtricitabine with atazanavir/ritonavir plus tenofovir/emtricitabine in treatment-naive patients with HIV-1 RNA levels ≥ 5000 copies/mL. As with the previously discussed trial, study participants were required to have a creatinine clearance rate ≥ 70 mL/min. Mean baseline CD4+ cell counts were 364-375 cells/mm3, and 11% to 15% of patients had CD4+ cell counts ≤ 200 cells/mm3 at baseline.
  • ATV, atazanavir; COBI, cobicistat; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; RTV, ritonavir; TDF, tenofovir.   Kimberly Y. Smith, MD, MPH: The results demonstrated comparable virologic response at Week 48 with both regimens. There was no clinically meaningful reduction in activity of the elvitegravir regimen among patients with higher vs lower baseline HIV-1 RNA levels, although the difference between these subgroups was slightly larger than that observed in the previously discussed elvitegravir study.   Joseph J. Eron, Jr., MD: In addition, similar to most studies of boosted PI regimens in treatment-naive patients, no resistance mutations emerged among patients receiving atazanavir/ritonavir who experienced virologic failure or rebound. However, 5 patients in the elvitegravir arm developed drug resistance, including primary integrase inhibitor–resistance mutations in 4 patients and M184V/I in 4 patients; it is notable that these values represent a small percentage of the overall population.   Kimberly Y. Smith, MD, MPH: It is also worth noting that, in both randomized comparative elvitegravir/cobicistat/tenofovir/ emtricitabine studies, the control arm performed very well; therefore, the fact that the elvitegravir-based regimen was able to perform as well as the control arm reflects very favorably on its efficacy.
  • ATV, atazanavir; COBI, cobicistat; EVG, elvitegravir; RTV, ritonavir.   Joseph J. Eron, Jr., MD: The safety analysis demonstrated similar rates of diarrhea and nausea between the 2 treatment arms. As would be expected, grade 3/4 hyperbilirubinemia occurred much more frequently in the atazanavir arm vs the elvitegravir arm. As with the previously discussed elvitegravir trial, serum creatinine increases were higher with elvitegravir-based treatment vs the control arm. Similar to the trend Dr. Smith noted in the previous trial, creatinine increases occurred very early during treatment, with the majority of the increase occurring during the first 2-4 weeks of therapy, which became relatively stable thereafter. This observation is useful to clinicians when planning a monitoring strategy. I usually schedule a follow-up visit with patients after approximately 4 weeks of treatment to assess response and tolerability. When the elvitegravir/cobicistat/tenofovir/emtricitabine pill becomes available, I will obtain creatinine levels at 4 weeks in patients who I start on this therapy and use the 4-week value as a new baseline value.
  • DTG, dolutegravir; EFV, efavirenz; tx, treatment; TLOVR, time to loss of virologic response.   Joseph J. Eron, Jr., MD: This slide depicts the results of a phase IIb study investigating another integrase inhibitor, dolutegravir, vs efavirenz in treatment-naive patients. It is important to underscore that each study arm included only approximately 50 patients. In total, 153 patients were randomized to 1 of 3 dolutegravir doses—10 mg, 25 mg, or 50 mg once daily—each administered in combination with 2 NRTIs.   The results showed that dolutegravir is very potent, with virologic efficacy similar to efavirenz. No cases of virologic failure occurred in the dolutegravir 50-mg/day dosing arm, and there was no emergence of integrase resistance mutations in any of the 3 dolutegravir treatment arms. Only 1 patient in the efavirenz arm experienced protocol-defined virologic failure, and this patient did not have evidence of NNRTI resistance; overall, therefore, the study population appears to have achieved a high level of adherence. In addition, similar to elvitegravir, dolutegravir was associated with small changes in mean serum creatinine. These changes are likely related to mild inhibition of tubular creatinine secretion, as a previous study demonstrated that dolutegravir had no effect on glomerular filtration rate measured by iohexol clearance. Based on the results of the phase IIb analysis, the 50-mg once-daily dose of dolutegravir was selected for ongoing clinical development and phase III testing.   Kimberly Y. Smith, MD, MPH: I agree that this study demonstrated dolutegravir to be very potent. It is important to recognize that dolutegravir is a once-daily integrase inhibitor that does not require boosting, unlike elvitegravir. It seemed to be well tolerated, with the exception of the change in creatinine that has been discussed in some detail. These data are very positive, and we look forward to the results of the phase III studies.
  • QD, once daily; TDF, tenofovir.   Joseph J. Eron, Jr., MD: The study shown on this slide evaluated the efficacy of GS-7340, a novel prodrug of tenofovir. When tenofovir disoproxil fumarate is administered, tenofovir is found circulating in the plasma; however, intracellular tenofovir diphosphate is the active drug. Because GS-7340 is rapidly taken up by cells, high intracellular concentrations of tenofovir diphosphate are achieved with relatively low circulating plasma concentrations of tenofovir. Therefore, it is hypothesized—although not yet proven—that GS‑7340 may have less tenofovir-associated toxicity, that is, less bone and renal toxicity. The other important feature of this agent is that the lower dosing level reduces the milligram footprint. Therefore, it will be easier to coformulate GS-7340 with other drugs into a single tablet. In fact, a single-tablet regimen consisting of darunavir/cobicistat/emtricitabine/GS-7340 has already been coformulated and is being studied in a planned phase II study. [1]   Kimberly Y. Smith, MD, MPH: This phase II dose-ranging trial follows a previous study presented 1 year ago that examined higher doses of this agent and found that even the lowest dose was associated with very high intracellular drug levels. The current study assessed the extent to which the dose could be reduced and still maintain virologic efficacy. Reference 1. ClinicalTrials.gov. Safety and efficacy of darunavir/cobicistat/emtricitabine/GS-7340 single tablet regimen vs cobicistat-boosted darunavir plus emtricitabine/tenofovir disoproxil fumarate fixed dose combination in HIV-1 infected, antiretroviral treatment naive adults. Available at: http://clinicaltrials.gov/ct2/show/NCT01565850. Accessed April 23, 2012.  
  • TDF, tenofovir.   Joseph J. Eron, Jr., MD: This slide shows that even at the relatively low dose of 25 mg/day, the median reduction in HIV-1 RNA was approximately 1.5 log10 copies/mL corresponding to an approximate 30-fold decrease in HIV-1 RNA levels over a 10- or 11-day period.   Kimberly Y. Smith, MD, MPH: I would underscore the point that it is not yet known if the toxicity profile of this agent differs from tenofovir disoproxil fumarate. Theoretically, it seems logical that toxicity should be reduced because plasma drug levels are lower, but that hypothesis will need to be supported with clinical data.
  • HIV Highlights From Seattle

    1. 1. HIV Highlights From Seattle CCO Independent Conference Coverage of the 2012 Conference on Retroviruses and Opportunistic Infections* March 5-8, 2012 Seattle, Washington *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.This program is supported by educational grants from Originally posted 3/20/2012 at clinicaloptions.com/ss/Seattle2012
    2. 2. HIV Highlights From Seattleclinicaloptions.com/hiv About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  This abbreviated slideset was posted to SlideShare to publicize the availability of the full slideset. These slides may not be published or posted online without permission from CCO (email permissions@clinicaloptions.com)DisclaimerThe materials published on the Clinical Care Options Web site reflect the views of the authors of theCCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providingeducational grants. The materials may discuss uses and dosages for therapeutic products that have notbeen approved by the United States Food and Drug Administration. A qualified healthcare professionalshould be consulted before using any therapeutic product discussed. Readers should verify all informationand data before treating patients or using any therapies described in these materials.
    3. 3. HIV Highlights From Seattleclinicaloptions.com/hiv Faculty Joseph J. Eron, Jr., MD Kimberly Y. Smith, MD, MPH Professor of Medicine and Associate Professor of Medicine Epidemiology Division of Infectious Diseases University of North Carolina Rush University Medical Center School of Medicine Chicago, Illinois Director, AIDS Clinical Trials Unit University of North Carolina Chapel Hill, North Carolina
    4. 4. HIV Highlights From Seattleclinicaloptions.com/hiv Faculty Disclosures Joseph J. Eron, Jr., MD, has disclosed that he has received grants for research support from Bristol-Myers Squibb, GlaxoSmithKline/ViiV, Merck, Taimed, and Tobira; has served as a consultant for Argos, Avexa, Bristol-Myers Squibb, Chimerix, Gilead Sciences, GlaxoSmithKline/ViiV, Inhibitex, Kainos Pharmaceutical, LabCorp, Merck, Myriad, Pfizer, Tibotec, Tobira, and Virco Laboratories; and has served on data and safety monitoring boards for Tibotec/Janssen and Vertex. Kimberly Y. Smith, MD, MPH, has disclosed that she has served as a consultant for Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, and ViiV.
    5. 5. Please review the slide notes for a complete discussion of each study by expert faculty Joseph J. Eron, Jr., MD, and Kimberly Y. Smith, MD, MPH
    6. 6. New Agents
    7. 7. HIV Highlights From Seattleclinicaloptions.com/hiv Elvitegravir/Cobicistat/TDF/FTC vs EFV/TDF/FTC in Treatment-Naive Patients  Multicenter, randomized, double-blinded, active-controlled phase III study Wk 48 Planned follow-up Stratified by primary analysis to Wk 192 baseline HIV-1 RNA > or ≤ 100,000 copies/mL Elvitegravir/Cobicistat/TDF/FTC QD + EFV/TDF/FTC placebo QD HIV-infected (n = 348) treatment-naive patients withHIV-1 RNA ≥ 5000 copies/mL, any CD4+ cell count, CLCR ≥ 70 mL/min EFV/TDF/FTC QD (N = 700) + Elvitegravir/Cobicistat/TDF/FTC placebo QD (n = 352)Sax P, et al. CROI 2012. Abstract 101.
    8. 8. HIV Highlights From Seattleclinicaloptions.com/hiv Elvitegravir/Cobicistat Regimen Noninferior to EFV Regimen at Wk 48 100 88 90 84 EVG/COBI/FTC/TDF 84 85 82 (n = 348) 80 EFV/FTC/TDF 60 (n = 352) 40 20 0 Overall HIV-1 RNA HIV-1 RNA ≤ 100,000 c/mL > 100,000 c/mL  Greater CD4+ count increase with EVG/COBI vs EFV: 239 vs 206 cells/mm3 (P = .009)  Among pts with confirmed virologic failure or rebound, resistance detected in 8/14 pts in EVG/COBI arm vs 8/17 patients in EFV arm – Primary integrase mutations and primary NNRTI mutations observed in 7 and 8 patients in EVG/COBI and EFV arms, respectively – All 8 pts in EVG/COBI arm had M184V/I mutation vs 2 pts in EFV arm; 3 and 2 had K65R, respectivelySax P, et al. CROI 2012. Abstract 101.
    9. 9. HIV Highlights From Seattleclinicaloptions.com/hiv Safety of Elvitegravir/Cobicistat Regimen vs EFV Regimen  Significantly greater incidence of nausea with EVG/COBI regimen  Significantly greater incidence of sleep disturbance, dizziness, rash with EFV regimen  1.4% of patients discontinued EVG/COBI regimen due to renal abnormalities vs no patients on EFV regimen – Significantly greater increase in median serum creatinine from baseline to Wk 48 in EVG/COBI group: 0.14 vs 0.01 mg/dL (P < .001) – Majority of increase in serum creatinine clearance occurred within 2 wks of starting treatment and progressed minimally over time  Significantly greater increases in total, LDL, and HDL cholesterol from baseline to Wk 48 in EFV vs EVG/COBI groups (all P ≤ .001)Sax P, et al. CROI 2012. Abstract 101.
    10. 10. HIV Highlights From Seattle clinicaloptions.com/hiv Elvitegravir/Cobicistat/TDF/FTC vs ATV/RTV + TDF/FTC in Tx-Naive Patients  Multicenter, randomized, double-blinded, active-controlled phase III study Wk 48 Planned follow-up Stratified by primary analysis to Wk 192 baseline HIV-1 RNA > or ≤ 100,000 copies/mL Elvitegravir/Cobicistat/TDF/FTC QD HIV-infected + ATV/RTV + FTC/TDF placebo QD treatment-naive patients, (n = 353)HIV-1 RNA ≥ 5000 copies/mL, any CD4+ cell count, CLCR ≥ 70 mL/min ATV/RTV + TDF/FTC QD (N = 708) + Elvitegravir/Cobicistat/TDF/FTC placebo QD (n = 355) DeJesus E, et al. CROI 2012. Abstract 627.
    11. 11. HIV Highlights From Seattleclinicaloptions.com/hiv Elvitegravir/Cobicistat Regimen Noninferior to ATV/RTV Regimen at Wk 48 100 90 93 90 EVG/COBI/FTC/TDF 87 85 82 (n = 353) 80 ATV/RTV + FTC/TDF 60 (n = 355) 40 20 0 Overall HIV-1 RNA HIV-1 RNA ≤ 100,000 c/mL > 100,000 c/mL  Similar CD4+ cell count increases in both study arms at Wk 48  Among pts with confirmed virologic failure or rebound, resistance detected in 5/12 pts in EVG/COBI arm vs 0/8 pts in ATV/RTV arm – 4/5 pts in EVG/COBI arm had M184V/I mutation; 4 had primary integrase mutationsDeJesus E, et al. CROI 2012. Abstract 627.
    12. 12. HIV Highlights From Seattleclinicaloptions.com/hiv Safety of Elvitegravir/Cobicistat Regimen vs ATV/RTV Regimen  Similar rates of grade 3/4 adverse events between arms: 13% in EVG/ COBI and 14% in ATV/RTV arm – Most common adverse events: diarrhea, nausea  Grade 3/4 hyperbilirubinemia more common in ATV/RTV group: 58% vs 1%  Significantly greater increase in median serum creatinine from baseline to Wk 48 in EVG/COBI group: 0.12 vs 0.08 mg/dL (P < .001) – Majority of increase in serum creatinine clearance occurred within 2 wks of starting treatment and progressed minimally over time  Significantly greater increase in median triglycerides from baseline to Wk 48 in ATV/RTV group: 23 vs 8 mg/dL (P = .006); otherwise no difference in lipid valuesDeJesus E, et al. CROI 2012. Abstract 627.
    13. 13. HIV Highlights From Seattleclinicaloptions.com/hiv SPRING-1: Phase IIb Trial of Dolutegravir vs Efavirenz in Tx-Naive Patients 100 88 < 50 copies/mL (TLOVR) (%)[1] 79 Patients With HIV-1 RNA 78 80 72 60 40 DTG 10 mg QD (n = 53) DTG 25 mg QD (n = 51) DTG 50 mg QD (n = 51) 20 EFV 600 mg (n = 50) 0 BL 4 8 1216 20 24 32 40 48 60 72 84 96 Wk  Comparable efficacy among arms  No cases of virologic failure in 50-mg arm  Minimal variations in serum creatinine observed across treatment arms – Alterations did not progress over time – Previous study showed DTG had no effect on glomerular filtration rate by iohexol clearance[2]1. Stellbrink HJ, et al. CROI 2012. Abstract 102LB. 2. Koteff J, et al. ICAAC 2011. Abstract A1-1728.
    14. 14. HIV Highlights From Seattle clinicaloptions.com/hiv GS-7340: Antiviral Activity of Novel Prodrug of Tenofovir  Lower TDF plasma concentrations, higher intracellular concentrations obtained with GS-7340 vs TDF – Hypothesized that this may result in greater efficacy, reduced toxicity  Previous study evaluated higher doses of GS-7340: 50 mg and 150 mg[1] 10 days TDF 300 mg QD (n = 6) HIV-infected GS-7340 8 mg QDtreatment-naive or -experienced patients with no genotypic (n = 9) resistance to TDF, GS-7340 25 mg QD HIV-1 RNA ≥ 2000 copies/mL, (n = 8) CD4+ count ≥ 200 cells/mm3[2] GS-7340 40 mg QD (N = 38) (n = 8) GS-7340 Placebo QD (n = 7) 1. Markowitz M, et al. CROI 2011. Abstract 152LB. 2. Ruane PJ, et al. CROI 2012. Abstract 103.
    15. 15. HIV Highlights From Seattleclinicaloptions.com/hiv Greater Antiviral Activity of GS-7340 25 mg and 40 mg vs TDF Dosing 0.5 Placebo (n = 7) 0.0 TDF 300 mg (n = 6) GS-7340 8 mg (n = 9) -0.5 GS-7340 25 mg (n = 8) GS-7340 40 mg (n = 8) -1.0 -1.5 -2.0 0 10 20 Day  Higher intracellular tenofovir diphosphate levels and lower circulating plasma tenofovir levels with GS-7340 vs TDFRuane PJ, et al. CROI 2012. Abstract 103.
    16. 16. For the rest of this presentation downloadthe full PowerPoint slideset for self-studyor use in your own educational presentationsat: clinicaloptions.com/ss/seattle2012Go Online for More CCO Coverage of CROI 2012:Capsule Summaries of key data from the meeting &CME-certified slideset incorporating a discussionamong 2 expert faculty exploring the clinical implicationsof each studyMore ways to connect with CCO:

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