The antiretroviral drug pipeline: Prospects and implications for future treatment research

Current Opinion in HIV and AIDS

Volumn 8, Issue 6, 2013, Pages 572-578

  Flexner, Charles ^a   Saag, Michael ^b  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

antiretroviral therapy; CCR5 antagonist; entry inhibitor; fusion inhibitor; integrase strand transfer inhibitor; nonnucleoside reverse transcriptase inhibitor; nucleoside reverse transcriptase inhibitor

Indexed keywords

ABACAVIR PLUS LAMIVUDINE; ALBUVIRTIDE; ANTIRETROVIRUS AGENT; BMS 626529; BMS 663068; CENICRIVIROC; COBICISTAT; DOLUTEGRAVIR; DORAVIRINE; EFAVIRENZ; EFAVIRENZ PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; ELVITEGRAVIR; EMTRICITABINE; ENFUVIRTIDE; ETRAVIRINE; FESTINAVIR; GSK 1265744; IBALIZUMAB; MARAVIROC; NEVIRAPINE; RALTEGRAVIR; RILPIVIRINE; RITONAVIR; STAVUDINE; TENOFOVIR; TENOFOVIR 3 HEXADECYLOXYPROPYL ESTER; TENOFOVIR ALAFENAMIDE; TENOFOVIR DISOPROXIL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VICRIVIROC;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; AREA UNDER THE CURVE; CREATININE BLOOD LEVEL; CREATININE CLEARANCE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; FANCONI RENOTUBULAR SYNDROME; GASTROINTESTINAL SYMPTOM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERLIPIDEMIA; INJECTION SITE REACTION; LOADING DRUG DOSE; MONOTHERAPY; NEPHROTOXICITY; PHOSPHATE BLOOD LEVEL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; TREATMENT FAILURE; VIRUS LOAD; VIRUS REPLICATION;

ANTI-RETROVIRAL AGENTS; DRUG DISCOVERY; HIV INFECTIONS; HUMANS;

EID: 84886085348     PISSN: 1746630X     EISSN: 17466318     Source Type: Journal    
DOI: 10.1097/COH.0000000000000011     Document Type: Review

References (27)

1. Clayden P, Ripin DHB. 2013 i-Base/TAG Pipeline Report. http://www.treatmentactiongroup.org/pipeline-report [Accessed on 30 August 2013].
2. World Health Organization Adult Guideline Development Group. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva: World Health Organization; 2013.
3. Genberg BL, Wilson IB, Bangsberg DR, et al., MACH14 Investigators. Patterns of antiretroviral therapy adherence and impact on HIV RNA among patients in North America. AIDS 2012; 26:1415-1423.
4. Flexner C. Antiretroviral agents and treatment of HIV infection. In: Brunton LL, Knowllman B, Chabner BA, editors. Goodman and Gilmans the pharmacological basis of therapeutics, 12th ed. New York: McGraw-Hill; 2011. pp. 1623-1663. . (Chap. 59).
5. Flexner C. HIV drug development: the next 25 years. Nat Rev Drug Disc 2007; 6:959-966.
6. Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med 2007; 357:2576-2588.
7. Crawford KW, Ripin DH, Levin AD, et al. Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement. Lancet Infect Dis 2012; 12:550-560.
8. Haraguchi K, Takeda S, Kubota Y, et al. From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4-ethynylstavudine-festinavir. Curr Pharm Des 2013; 19:1880-1897.
9. Ruane PJ, Dejesus E, Berger D, et al. Antiviral activity, safety, and pharmacokinetics/ pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr 2013; 63:449-455.
10. Lanier ER, Ptak RG, Lampert BM, et al. Development of hexadecyloxypropyl tenofovir (CMX157) for treatment of infection caused by wild-type and nucleoside/nucleotide-resistant HIV. Antimicrob Agents Chemother 2010; 54:2901-2909.
11. Anderson M, Gilmartin J, Robberechts M, et al. Safety and antiviral activity of MK-1439, a novel nonnucleoside reverse transcriptase inhibitor (NNRTI), in treatment-naive HIV-infected patients. 20th Conference on Retroviruses and Opportunistic Infections, March 3-6 2013, Atlanta, GA, Alexandria, VA, CROI, LLC; 2013 [Abstract 100].
12. Nettles RE, Schurmann D, Zhu L, et al. Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects. J Infect Dis 2012; 206:1002-1011.
13. Ray N, Hwang C, Healy MD, et al. Prediction of virologic response and assessment of resistance emergence to the HIV-1 attachment inhibitor BMS-626529 during 8-day monotherapy with its prodrug BMS-663068. J Acquir Immune Defic Syndr 2013; 64:7-15.
14. Jacobson JM, Kuritzkes DR, Godofsky E, et al. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1- infected adults. Antimicrob Agents Chemother 2009; 53:450-457.
15. Swindells S, Flexner C, Fletcher CV, Jacobson JM. The critical need for alternative antiretroviral formulations and obstacles to their development. J Infect Dis 2011; 204:669-674.
16. Chong H, Yao X, Zhang C, et al. Biophysical property and broad anti-HIV activity of albuvirtide, a 3-maleimimidopropionic acid-modified peptide fusion inhibitor. PLoS One 2012; 7:e32599.
17. Wilkin TJ, Su Z, Krambrink A, et al., AIDS Clinical Trials Group A5211 Study Team. Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV- 1-infected, treatment-experienced patients. J Acquir Immunodef Syndr 2010; 54:470-476.
18. Henrich TJ, Kuritzkes DR. HIV-1 entry inhibitors: recent development and clinical use. Curr Opin Virol 2013; 3:51-57.
19. Gathe J, Cade J, DeJesus E, et al. Week-24 primary analysis of cenicriviroc vs efavirenz, in combination with emtricitabine/tenofovir, in treatment-naive HIV- 1 adults with CCR5-tropic virus. Program and Abstracts of the 20th Conference on Retroviruses and Opportunistic Infections, March 3-6 2013, Atlanta, GA, Alexandria, VA, CROI, LLC; 2013 [abstract 106LB].
20. Stellbrink HJ, Reynes J, Lazzarin A, et al. Dolutegravir in antiretroviral-nave adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013; 27:1771-1778.
21. Walmsley S, Antela A, Clumeck N, et al. Dolutegravir (DTG; S/GSK1349572) abacavir/lamivudine once daily statistically superior to tenofovir/ emtricitabine/ efavirenz: 48-week results - SINGLE (ING114467). 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 9-12 September 2012; San Francisco, CA; 2014 [Abstract H-556b].
22. Cahn P, Pozniak AL, Mingrone H, et al., on behalf of the extended SAILING Study Team. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, noninferiority SAILING study. Lancet 2013; 382:700-708.
23. Koteff J, Borland J, Chen S, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol 2013; 75:990-996.
24. Dooley KE, Sayre P, Borland J, et al. Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr 2013; 62:21-27.
25. Gallant JE, Koenig E, Andrade-Villanueva J, et al. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results. J Infect Dis 2013; 208:32-39.
26. 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; 61:32-40.
27. Ward D, Crofoot G, Shamblaw D, et al. Efficacy and safety of elvitegravir/ cobicistat/emtricitabine/tenofovir DF from an integrated analysis of phase 2 and 3 clinical trials. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC), 9-12 September 2012; San Francisco, CA; 2014 [Abstract H-555].