HIV integrase inhibitors: A new era in the treatment of HIV

Expert Opinion on Pharmacotherapy

Volumn 16, Issue 9, 2015, Pages 1313-1324

  Blanco, Jose Luis ^a   Whitlock, Gary ^b   Milinkovic, Ana ^c   Moyle, Graeme ^b  

^a HOSPITAL CLÍNIC   (Spain)

^b CHELSEA AND WESTMINSTER HOSPITAL   (United Kingdom)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Dolutegravir; Elvitegravir; HIV; Integrase inhibitors; Raltegravir

Indexed keywords

DOLUTEGRAVIR; ELVITEGRAVIR; INTEGRASE INHIBITOR; RALTEGRAVIR; 2 PYRROLIDONE DERIVATIVE; FUSED HETEROCYCLIC RINGS; QUINOLONE DERIVATIVE;

ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MULTICENTER STUDY (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; UNSPECIFIED SIDE EFFECT; CLINICAL TRIAL (TOPIC); HIV INFECTIONS;

CLINICAL TRIALS AS TOPIC; HETEROCYCLIC COMPOUNDS, 3-RING; HIV INFECTIONS; HIV INTEGRASE INHIBITORS; HUMANS; PYRROLIDINONES; QUINOLONES; RALTEGRAVIR POTASSIUM;

EID: 84929916124     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2015.1044436     Document Type: Review

References (51)

1. Hazuda DJ, Felock P, Witmer M, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000;287: 646-50
2. Grinstein B, De Castro N, Arnold V, et al. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial. Lancet Infect Dis 2014. 14, 6, 459-67
3. Lennox JL, Dejesus E, Berger DS, et al. Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr 2010;55:39-48
4. Rockstroh JK, Lennox JL, Dejesus E, et al. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatmentnaive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis 2011;53:807-16
5. DeJesus E, Lazzarin A, Lennox AJ, et al. Metabolic profiles and body composition changes in treatment-nave HIV-infected patients treated with raltegravir 400 mg bid-based vs. Efavirenz 600 mg qhs-based Combination Therapy: 48-Week Data. ICAAC 2009 H-329
6. Landovitz RJ, Ribaudo HJ, Ofotokun I, et al. Efficacy and Tolerability of Atazanavir, Raltegravir, or Darunavir with FTC/Tenofovir: ACTG 5257. Abstract 85, CROI 2014, Boston, MA, March 3-6, 2014
7. Eron JJ Jr, Rockstroh JK, Reynes J, et al. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis 2011;11:907-15
8. Eron JJ, Young B, Cooper DA, et al. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet 2010;375(9712):396-407
9. Martnez E, DAlbuquerque PM, Llibre JM, et al. Changes in cardiovascular biomarkers in HIVinfected patients switching from ritonavir-boosted protease inhibitors to raltegravir. AIDS 2012;26: 2315-26
10. Curran A, Martinez E, Saumoy M, et al. Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy. AIDS 2012;26:475-81
11. Lake JE, McComsey GA, Hulgan TM, et al. A Randomized trial of raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in hiv-infected women with lipohypertrophy. AIDS Patient Care STDS 2012;26(9):532-40
12. Vispo E, Mena A, Maida I, et al. Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C. J Antimicrob Chemother 2010;65:543-7
13. Eron JJ, Cooper DA, Steigbigel RT, et al. Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials. Lancet Infect Dis 2013;13: 587-96
14. Pozniak A, Markowitz M, Mills A, et al. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis 2014;14(7):590-9
15. Arribas J, Pialoux G, Gathe J, et al. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, noninferiority trial. Lancet Infect Dis 2014;14(7):581-9
16. Cohen C, Elion R, Ruane P, et al. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS 2011;25(6):F7-12
17. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents regimens. Available from: http://aidsinfo.nih.gov/guidelines [Last accessed 4 July 2014]
18. Sax PE, DeJesus E, Mills A, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus coformulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 2012;379(9835):2439-48
19. Zolopa A, Sax PE, DeJesus E, et al. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr 2013;63(1):96-100
20. Wohl DA, Cohen C, Gallant JE, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr 2014;65(3):e118-20
21. DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012;379(9835):2429-38
22. Rockstroh JK, DeJesus E, Henry K, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavirboosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr 2013;62(5):483-6
23. Clumeck N, Molina JM, Henry K, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr 2014;65(3):e121-4
24. Molina JM, LaMarca A, Andrade-Villanueva J, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatmentexperienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis 2012;12(1):27-35
25. Steigbigel RT, Cooper DA, Kumar PN, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008;359:339-54
26. Katlama C, Haubrich R, Lalezari J, et al. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS 2009;23:2289-300
27. Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 2008;359:1429-41
28. Llibre JM, Pulido F, Garcia F, et al. Genetic barrier to resistance for dolutegravir. AIDS Rev 2015;17(1):56-64
29. Blanco Arevalo JL, Whitlock GG. Dolutegravir: an exciting new kid on the block. Expert Opin Pharmacother 2014;15(4):573-82
30. Walmsley S, Antela A, Clumeck N, et al. Dolutegravir plus Abacavir-Lamivudine for the treatment of HIV-1 Infection. N Engl J Med 2013;369:1807-18
31. Raffi F, Rachlis A, Stellbrink HJ, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013;381:735-43
32. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experience, intergrase-inhibitor-nave adults with HIV: week 48 results from the randomized, double-blind, non-inferiority SAILING study. Lancet 2013;382(9893):700-8
33. Castagna A, Maggiolo F, Penco G, et al. Dolutegravir in Antiretroviral-Experienced Patients with Raltegravirand/or Elvitegravir-Resistant HIV-1: 24-week Results of the Phase III VIKING-3 Study. J Infect Dis 2014;210(3):354-62
34. Clotet B, Feinberg J, Van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-nave adults with HIV-1 infection (FLAMINGO): 48 week results from the randomized open-label phase 3b study. Lancet 2014;383(9936):2222-31
35. Gandhi RT, Zheng L, Bosch RJ, et al. The effect of raltegravir intensification on low-level residual viremia in HIVinfected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med 2010;7:e1000321
36. McMahon D, Jones J, Wiegand A, et al. Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis 2010;50:912-19
37. Buzon MJ, Massanella M, Llibre JM, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed 48-week study. Antivir Ther 2012;17:355-6
38. Smurzynski M, Wu K, Letendre S, et al. Effects of central nervous system antiretroviral prenetration on cognitive functioning in the ALLRT cohort. AIDS 2011;25(3):357-65
39. Yilmaz A, Gisslen M, Sudich S, et al. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection. PLoS ONE 2009;4:e6877
40. Letendre S, Mills A, Tashima K, et al. ING116070: A study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects. Clin Infect Dis 2014;59(7):1032-7
41. Sax P, Zolopa A, Brar I, et al. Tenofovir alafenamide vs tenofovir disoproxil fumarate in single Tablet regimen for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr 2014;67:52-8
42. Martinez E, Larrousse M, Llibre JM, et al. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS 2010;24(11):1697-707
43. Blanco JL, Montaner J, Marconi VC, et al. Lower Prevalence of Drug Resistance Mutations at First-Line Virological Failure to First-line Therapy with Atripla vs. Tenofovir +Emtricitabine/Lamivudine+Efavirenz Administered on a Multiple Tablet Therapy. AIDS 2014;28(17):2531-9
44. German P, Liu HC, Szwarcberg J, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr 2012;61(1):32-40
45. Available from: http://www.gilead.com/~/media/Files/pdfs/medicines/hiv/stribild/stribild-pi.pdf
46. Available from: http://www.ema.europa. eu/docs/en-GB/document-library/EPARProduct-Information/human/002572/WC500153014.pdf
47. Stray KM, Bam RA, Birkus G, et al. Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrob Agents Chemother 2013;57(10):4982-9
48. Maggi P, Montinaro V, Rusconi S, et al. The problem of renal function monitoring in patients treated with the novel antiretroviral drugs. HIV Clin Trials 2014;15(3):87-91
49. Hightower KE, Wang R, Deanda F, et al. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes. Antimicrob Agents Chemother 2011;55(10):4552-9
50. Weller S, Chen S, Bolard J, et al. Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food. J Acquir Immune Defic Syndr 2014;66:393-8
51. Reese MJ, Savina PM, Generaux GT, et al. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos 2013;41(2):353-61