Protection against rectal chimeric simian/human immunodeficiency virus transmission in macaques by rectal-specific gel formulations of maraviroc and tenofovir

Journal of Infectious Diseases

Volumn 212, Issue 12, 2015, Pages 1988-1995

  Dobard, Charles W ^a   Taylor, Andrew ^b   Sharma, Sunita ^a   Anderson, Peter L ^c   Bushman, Lane R ^c   Chuong, Dinh ^a   Pau, Chou Pong ^a   Hanson, Debra ^a   Wang, Lin ^d   Garcia Lerma, J Gerardo ^a   McGowan, Ian ^d   Rohan, Lisa ^d   Heneine, Walid ^a  

^a CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

^b Total Solutions Inc   (United States)

^c UNIVERSITY OF COLORADO   (United States)

^d UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

HIV prevention; Macaque model; Maraviroc; Rectal microbicides; Repeat challenge; Tenofovir

Indexed keywords

MARAVIROC; PLACEBO; TENOFOVIR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CYCLOHEXANE DERIVATIVE; GEL; TRIAZOLE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG FORMULATION; DRUG TISSUE LEVEL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VIVO STUDY; LIMIT OF DETECTION; LYMPHOCYTE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; RECTUM BIOPSY; RHESUS MONKEY; SIMIAN IMMUNODEFICIENCY VIRUS; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS LOAD; VIRUS TRANSMISSION; ADMINISTRATION AND DOSAGE; ANIMAL; CROSSOVER PROCEDURE; DISEASE MODEL; DISEASE TRANSMISSION; GEL; MACACA; PREVENTION AND CONTROL; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; TOPICAL DRUG ADMINISTRATION; TREATMENT OUTCOME;

ADMINISTRATION, TOPICAL; ANIMALS; ANTI-HIV AGENTS; CROSS-OVER STUDIES; CYCLOHEXANES; DISEASE MODELS, ANIMAL; DISEASE TRANSMISSION, INFECTIOUS; GELS; MACACA; PLACEBOS; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; TENOFOVIR; TREATMENT OUTCOME; TRIAZOLES;

EID: 84959378160     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiv334     Document Type: Article

References (41)

1. UNAIDS. Report on the global HIV/AIDS epidemic 2013. Geneva: UNAIDS, 2013.
2. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329:1168-74.
3. Mayer KH, Maslankowski LA, Gai F, et al. Safety and tolerability of te-nofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 2006; 20:543-51.
4. Friend DR, Kiser PF. Assessment of topical microbicides to prevent HIV-1 transmission: Concepts, testing, lessons learned. Antivir Res 2013; 99:391-400.
5. Schwartz JL, Rountree W, Kashuba AD, et al. A multi-compartment, single and multiple dose pharmacokinetic study of the vaginal candidate microbicide 1% tenofovir gel. PLoS One 2011; 6:e25974.
6. Beyrer C, Baral SD, van Griensven F, et al. Global epidemiology of HIV infection in men who have sex with men. Lancet 2012; 380:367-77.
7. El-Sadr WM, Mayer KH, Hodder SL. AIDS in America-forgotten but not gone. N Engl J Med 2010; 362:967-70.
8. Beyrer C. Global prevention of HIV infection for neglected populations: men who have sex with men. Clin Infect Dis 2010; 50:S108-13.
9. Gorbach PM, Manhart LE, Hess KL, Stoner BP, Martin DH, Holmes KK. Anal intercourse among young heterosexuals in three sexually transmitted disease clinics in the United States. Sex Transm Dis 2009; 36:193-8.
10. Herbenick D, Reece M, Schick V, Sanders SA, Dodge B, Fortenberry JD. Sexual behavior in the united states: results from a national probability sample of men and women ages 14-94. J Sex Med 2010; 7:255-65.
11. Kalichman SC, Pinkerton SD, Carey MP, et al. Heterosexual anal intercourse and HIV infection risks in the context of alcohol serving venues, Cape Town, South Africa. BMC Public Health 2011; 11:807.
12. Kalichman SC, Simbayi LC, Cain D, Jooste S. Heterosexual anal intercourse among community and clinical settings in Cape Town, South Africa. Sex Transm Infect 2009; 85:411-5.
13. Anton PA, Cranston RD, Kashuba A, et al. RMP-02/MTN-006: a phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fuma-rate. AIDS Res Hum Retroviruses 2012; 28:1412-21.
14. Dezzutti CS, Russo J, Wang L, et al. Development of HIV-1 rectal-specific microbicides and colonic tissue evaluation. PLoS One 2014; 9.
15. McGowan I, Hoesley C, Cranston RD, et al. A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007). PLoS One 2013; 8:e60147.
16. Rohan LC, Moncla BJ, Ayudhya RPKN, et al. In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PLoS One 2010; 5.
17. Leyva FJ, Bakshi RP, Fuchs EJ, et al. Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides. AIDS Res Hum Retrov 2013; 29:1487-95.
18. Cranage M, Sharpe S, Herrera C, et al. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med 2008; 5:e157; discussion e157.
19. Malcolm RK, Forbes CJ, Geer L, et al. Pharmacokinetics and efficacy of a vaginally administered maraviroc gel in rhesus macaques. J Antimi-crob Chemother 2013; 68:678-83.
20. Parikh UM, Dobard C, Sharma S, et al. Complete protection from repeated vaginal simian-human immunodeficiency virus exposures in macaques by a topical gel containing tenofovir alone or with emtricita-bine. J Virol 2009; 83:10358-65.
21. Veazey RS, Ketas TJ, Dufour J, et al. Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor. J Infect Dis 2010; 202:739-44.
22. Parra J, Portilla J, Pulido F, et al. Clinical utility of maraviroc. Clin Drug Investig 2011; 31:527-42.
23. Perry CM. Maraviroc: a review of its use in the management of CCR5-tropic HIV-1 infection. Drugs 2010; 70:1189-213.
24. Food and Drug Administration. FDA approves first medication to reduce HIV risk. 16 July 2012.
25. Dobard C, Sharma S, Parikh UM, et al. Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors. Sci Transl Med 2014; 6:227ra35.
26. Dobard C, Sharma S, Martin A, et al. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by teno-fovir gel and its relationship to drug levels in tissue. J Virol 2012; 86:718-25.
27. Massud I, Aung W, Martin A, et al. Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues. J Virol 2013; 87:8952-61.
28. Bushman LR, Kiser JJ, Rower JE, et al. Determination of nucleoside analog mono-, di-, and tri-phosphates in cellular matrix by solid phase extraction and ultra-sensitive LC-MS/MS detection. J Pharm Biomed Anal 2011; 56:390-401.
29. Garcia-Lerma JG, Cong M, Mitchell J, et al. Intermittent prophylaxis with oral Truvada protects macaques form rectal SHIV infection. Sci Transl Med 2010; 2:14ra4.
30. Garcia-Lerma JG, Otten RA, Qari SH, et al. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with em-tricitabine and tenofovir. PLoS Med 2008; 5:291-9.
31. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylax-is for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587-99.
32. Srinivas RV, Fridland A. Antiviral activities of 9-R-2-phosphonome-thoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl) PMPA against various drug-resistant human immunodeficiency virus strains. Antimicrob Agents Chemother 1998; 42:1484-7.
33. Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427, 857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother 2005; 49:4721-32.
34. Yang KH, Hendrix C, Bumpus N, et al. A multi-compartment single and multiple dose pharmacokinetic comparison of rectally applied te-nofovir 1% gel and oral tenofovir disoproxil fumarate. PLoS One 2014; 9:e106196.
35. Radzio J, Aung W, Holder A, et al. Prevention of vaginal SHIV transmission in macaques by a coitally-dependent Truvada regimen. PLoS One 2012; 7.
36. Hudgens MG, Gilbert PB. Assessing vaccine effects in repeated low-dose challenge experiments. Biometrics 2009; 65:1223-32.
37. Elisabet G CC, Coll J, Moltó J, et al. Oral single-dose maraviroc does not prevent ex vivo HIV infection of rectal mucosa in healthy HIV-1-negative human volunteers in tissue explants [abstract 964]. In: Program and abstracts of the 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, WA: CROI, 2015.
38. Poles MA, Elliott J, Taing P, Anton PA, Chen ISY. A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection. J Virol 2001; 75:8390-9.
39. Hunt PW, Shulman NS, Hayes TL, et al. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood 2013; 121: 4635-46.
40. North TW, Villalobos A, Hurwitz SJ, et al. Enhanced antiretroviral therapy in rhesus macaques improves RT-SHIV viral decay kinetics. Anti-microb Agents Chemother 2014; 58:3927-33.
41. Tsibris AMN, Pal U, Schure AL, et al. SHIV-162P3 infection of rhesus macaques given maraviroc gel vaginally does not involve resistant viruses. PLoS One 2011; 6.