Antiretroviral pharmacology in mucosal tissues

Journal of Acquired Immune Deficiency Syndromes

Volumn 63, Issue SUPPL. 2, 2013, Pages

  Thompson, Corbin G ^a   Cohen, Myron S ^b   Kashuba, Angela D M ^a,b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Antiretrovirals; Mucosal tissues; Pharmacokinetics; Preexposure prophylaxis

Indexed keywords

ABACAVIR; AMPRENAVIR; ANTIRETROVIRUS AGENT; ATAZANAVIR; DAPIVIRINE; DARUNAVIR; DIDANOSINE; DOLUTEGRAVIR; EFAVIRENZ; EMTRICITABINE; ETRAVIRINE; INDINAVIR; LAMIVUDINE; LOPINAVIR; MARAVIROC; MULTIDRUG RESISTANCE PROTEIN; NEVIRAPINE; RALTEGRAVIR; RILPIVIRINE; RITONAVIR; SAQUINAVIR; STAVUDINE; TENOFOVIR; ZALCITABINE; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CHEMOPROPHYLAXIS; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG EXPOSURE; DRUG HALF LIFE; DRUG TISSUE LEVEL; FEMALE GENITAL SYSTEM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION PREVENTION; LONG TERM EXPOSURE; MEN WHO HAVE SEX WITH MEN; MINIMUM INHIBITORY CONCENTRATION; MUCOSA; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; RECTUM MUCOSA; SPERM; VAGINA RING; VIRUS PATHOGENESIS; VIRUS SHEDDING; VIRUS TRANSMISSION;

ANIMALS; ANTI-HIV AGENTS; COLON; COMPUTER SIMULATION; DRUG DOSAGE CALCULATIONS; FEMALE; GENITALIA, FEMALE; HIV INFECTIONS; HUMANS; MALE; MODELS, THEORETICAL; MUCOUS MEMBRANE; RECTUM; TREATMENT OUTCOME;

EID: 84880247949     PISSN: 15254135     EISSN: 10779450     Source Type: Journal    
DOI: 10.1097/QAI.0b013e3182986ff8     Document Type: Article

References (99)

1. Van Sighem AI, Gras LA, Reiss P, et al. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of unin-fected individuals. AIDS. 2010;24:1527-1535.
2. UNAIDS. AIDS Epidemic Update 2012. Available at: http://www.unaids.org/ en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/ 20121120-UNAIDS-Global-Report-2012-en.pdf. Accessed March 19, 2013.
3. Kashuba ADM, Dyer JR, Kramer LM, et al. Antiretroviral-drug concentrations in semen: implications for sexual transmission of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1999; 43:1817-1826.
4. Vernazza PL, Gilliam BL, Flepp M, et al. Effect of antiviral treatment on the shedding of HIV-1 in semen. AIDS. 1997;11:1249-1254.
5. Vernazza PL, Troiani L, Flepp MJ, et al. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. AIDS. 2000;14:117-121.
6. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505.
7. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zudovudine treatment. N Engl J Med. 1994;331:1173-1180.
8. Cardo DM, Culver DH, Ciesielski CA. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med. 1997;337:1485-1490.
9. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010; 363:2587-2599.
10. Karim QA, Karim SSA, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, and antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329:1168-1174.
11. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411-422.
12. Marrazzo J, Ramjje G, Nair G, et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofo-vir gel in the VOICE study (MTN 003). Paper presented at: XX Conference on Retroviruses and Opportunistic Infections; March 4, 2013; Atlanta, GA.
13. Whelton A, Blanco L, Carter G. Therapeutic implications of doxycycline and cephalothin concentrations in the female genital tract. Obstet Gyne-col. 1980;55:28-32.
14. Gall S, Hemsell DL, McGregor J, et al. Tissue penetration of meropenem in patients undergoing gynecologic surgery. Clin Infect Dis. 1997;24 (suppl 2):S178-S180.
15. Martens MG, Maccato M, Van Hook C, et al. Penetration of trovaflox-acin into gynecologic tissues. Am J Surg. 1998;176(suppl):18S-22S.
16. Iliopoulou A, Thin RN, Turner P. Fluorimetric and microbiological assays of erythromycin concentrations in plasma and vaginal washings. Br J Vener Dis. 1981;57:263-267.
17. Heykants JJ, Woestenborghs RJ, Bisschop MP, et al. Distribution of oral ketoconazole to vaginal tissue. Eur J Clin Pharmacol. 1982;23:331-333.
18. Larosa E, Cauwenbergh G, Cilli P, et al. Itraconazole pharmacokinetics in the female genital tract: plasma and tissue levels in patients undergoing hysterectomy after a single dose of 200 mg itraconazole. Eur J Obstet Gynecol Reprod Biol. 1986;23:85-89.
19. Dumond JB, Yeh RF, Patterson KB, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre-and post-exposure prophylaxis. AIDS. 2007;21:1899-1907.
20. Dumond JB, Patterson KB, Pecha AL, et al. Maraviroc concentrations in the cervicovaginal fluid and vaginal tissue of HIV-negative women. J Acquir Immune Defic Syndr. 2009;51:546-553.
21. Min SS, Corbett AH, Rezk N, et al. Protease inhibitor and nonnucleoside reverse transcriptase inhibitor concentrations in the genital tract of HIV-1-infected women. J Acquir Immune Defic Syndr. 2004;37:1577-1580.
22. Karim SSA, Kashuba ADM, Werner L, et al. Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women. Lancet. 2011;378:279-281.
23. Hladik F, Hope TJ. HIV infection of the genital mucosa in women. Curr HIV/AIDS Rep. 2009;6:20-28.
24. Haase AT. Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med. 2011;62:127-139.
25. Miller CJ, Li Q, Abel K, et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol. 2005;79:9217-9227.
26. Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol. 2000;74:6087-6095.
27. Padian NS, Van Der SA, Ramjee G, et al. Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet. 2008;370:251-261.
28. Tebit DM, Ndembi N, Weinberg A, et al. Mucosal transmission of human immunodeficiency virus. Curr HIV Res. 2012;10:3-8.
29. Lane T, Pettifor A, Pascoe S, et al. Heterosexual anal intercourse increases risk of HIV infection among young South African men. AIDS. 2006;20:119-132.
30. Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2012;3:112re4.
31. Kwara A, Delong A, Rezk N, et al. Antiretroviral drug concentrations and HIV RNA in the genital tract of HIV-infected women receiving long-term highly active antiretroviral therapy. Clin Infect Dis. 2008; 46:719-725.
32. Else LJ, Taylor S, Back DJ, et al. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract. Antivir Ther. 2011;16:1149-1167.
33. Brown KC, Patterson KB, Jennings SH, et al. Single-and multiple-dose pharmacokinetics of darunavir plus ritonavir and etravirine in semen and rectal tissue of HIV-negative men. J Acquir Immune Defic Syndr. 2012; 61:138-144.
34. Patterson K, Jennings S, Falcon R, et al. Darunavir, ritonavir, and etravirine pharmacokinetics in the cervicovaginal fluid and blood plasma of HIV-infected women. Antimicrob Agents Chemother. 2011; 55:1120-1122.
35. Jones A, Talameh J, Patterson K. First-dose and steady-state pharmaco-kinetics of raltegravir in the genital tract of HIV negative women. Paper presented at: X International Workshop on Clinical Pharmacology of HIV Therapy; April 16, 2009; Amsterdam, The Netherlands.
36. Yeh RF, Rezk NL, Kashuba ADM, et al. Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women. Antimicrob Agents Chemother. 2009;53:2367-2374.
37. Launay O, Tod M, Louchahi K, et al. Differential diffusions of in-dinavir and lopinavir in genital secretions of human immunodeficiency virus-infected women. Antimicrob Agents Chemother. 2004; 48:632-634.
38. Clavel C, Mandelbrot L, Marcelin A. Raltegravir concentrations in the cervicovaginal compartment exceed the median inhibitory concentration in HIV-1-infected women treated with a raltegravir-containing regimen: DIVA 01 Study. Paper presented at: XVII Conference on Retroviruses and Opportunistic Infections; February 18, 2010; San Francisco, CA.
39. Greener B, Adams J, Patterson K. Single and multiple dose dolutegravir pharmacokinetics in the genital tract and colorectum of HIV-negative men and women. Paper presented at: XX Conference on Retroviruses and Opportunistic Infections; March 5, 2013; Atlanta, GA.
40. Brown KC, Patterson KB, Malone S, et al. Single and multiple dose pharmacokinetics of maraviroc in saliva, semen, and rectal tissue of healthy HIV-negative men. J Infect Dis. 2011;203:1484-1490.
41. Else LJ, Jackson A, Tija J. Pharmacokinetics of long-acting rilpivirine in plasma, genital tract, and rectum of HIV-negative females and males administered a single 600mg dose. Paper presented at: XIII International Workshop on Clinical Pharmacology of HIV Therapy; April 17, 2012; Barcelona, Spain.
42. Andrews C, Gettie A, Russell-Lodrigue K, et al. Long-acting parenteral formulation of GSK1265744 protects macaques against repeated intra-rectal challenges with SHIV. Paper presented at: XX Conference on Retroviruses and Opportunistic Infections; 2013; Atlanta, GA.
43. Nuttall J, Kashuba A, Wang R, et al. Pharmacokinetics of tenofovir following intravaginal and intrarectal administration of tenofovir gel to rhesus macaques. Antimicrob Agents Chemother. 2012;56: 103-109.
44. Johnson TJ, Clark MR, Albright TH, et al. A 90-day tenofovir reservoir intravaginal ring for mucosal HIV prophylaxis. Antimicrob Agents Chemother. 2012;56:6272-6283.
45. Nel A, Smythe S, Youg K, et al. Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women. J Acquir Immune Defic Syndr. 2009;51:416-423.
46. Lin JH. Tissue distribution and pharmacodynamics: a complicated relationship. Curr Drug Metab. 2006;7:39-65.
47. Theuretzbacher U. Tissue penetration of antibacterial agents: how should this be incorporated into pharmacodynamic analyses? Curr Opin Pharmacol. 2007;7:498-504.
48. Henry K, Chinnock BJ, Quinn RP, et al. Concurrent zidovudine levels in semen and serum determined by radioimmunoassay in patients with AIDS or AIDS-related complex. JAMA. 1988;259:3023-3026.
49. Cao YJ, Hendrix CW. Male genital tract pharmacology: developments in quantitative methods to better understand a complex peripheral compartment. Clin Pharmacol Ther. 2008;83:401-412.
50. Kis O, Robillard K, Chan GNY, et al. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci. 2010;31:22-35.
51. Finstad CL, Saigo PE, Rubin SC, et al. Immunohistochemical localization of P-glycoprotein in adult human ovary and female genital tract of patients with benign gynecological conditions. J Histochem Cytochem. 1990;38:1677-1681.
52. Nicol M, Fedoriw Y, Mathews M, et al. Gene and protein expression of drug transporters in vaginal, cervical, and rectal tissues: implications for drug disposition in HIV prevention. Paper presented at: XX Conference on Retroviruses and Opportunistic Infections; March 5, 2013; Atlanta, GA.
53. Zhou M, Veenstra T. Mass spectrometry: m/z 1983-2008. Biotechniques. 2008;44:667-668, 670.
54. Reyzer ML, Caprioli RM. MALDI-MS-based imaging of small molecules and proteins in tissues. Curr Opin Chem Biol. 2007;11:29-35.
55. Zavalin A, Todd EM, Rawhouser PD, et al. Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS. J Mass Spectrom. 2012;47:1473-1481.
56. Meesters RJW, Van Kampen JJ, Scheuer RD, et al. Determination of the antiretroviral drug tenofovir in plasma from HIV-infected adults by ultra-fast isotope dilution MALDI-triple quadrupole tandem mass spectrome-try. J Mass Spectrom. 2011;46:282-289.
57. Srivastava HK, Bohari MH, Sastry GN. Modeling anti-HIV compounds: the role of analogue-based approaches. Curr Comput Aided Drug Des. 2012;8:224-248.
58. Zhang L, Zhu H, Oprea TI, et al. QSAR modeling of the blood-brain barrier permeability for diverse organic compounds. Pharm Res. 2008; 25:1902-1914.
59. Sedykh A, Fourches D, Duan J, et al. Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013;30:996-1007.
60. Thompson C, Sedykh A, Nicol M, et al. Prediction of antiretroviral drug penetration into the female genital tract using a novel QSAR model. Paper presented at: XIV International Workshop on Clinical Pharmacology of HIV; April 23, 2013; Amsterdam, The Netherlands.
61. Perno CF, Cooney D a, Gao WY, et al. Effects of bone marrow stimulatory cytokines on human immunodeficiency virus replication and the antiviral activity of dideoxynucleosides in cultures of monocyte/ma-crophages. Blood. 1992;80:995-1003.
62. Gao WY, Agbaria R, Driscoll JS, et al. Divergent anti-human immunodeficiency virus activity and anabolic phosphorylation of 29, 39-dideoxynucleoside analogs in resting and activated human cells. J Biol Chem. 1994;269: 12633-12638.
63. Robbins B, Wilcox C, Fridland A. Metabolism of tenofovir and didano-sine in quiescent or stimulated human peripheral blood mononuclear cells. Pharmacotherapy. 2003;23:695-701.
64. Mayer KH, Venkatesh KK. Interactions of HIV, other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquistion. Am J Reprod Immunol. 2012;65:308-316.
65. Brabin L. Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression. AIDS Patient Care STDs. 2002;16:211-221.
66. Mingjia L, Short R. How oestrogen or progesterone might change a woman's susceptibility to HIV-1 infection. Aust N Z J Obstet Gynaecol. 2002; 42:472-475.
67. Perelson AS, Neumann AU, Markowitz M, et al. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271:1582-1586.
68. Hawkins T, Veikley W, St. Claire RL, et al. Intracellular pharmacoki-netics of tenofovir diphosphate, in patients receiving triple-nucleoside regimens. J Acquir Immune Defic Syndr. 2005;39:406-411.
69. Adams JL, Sykes C, Menezes P, et al. Tenofovir diphosphate and em-tricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence? J Acquir Immune Defic Syndr. 2013 [Epub ahead of print].
70. Kashuba ADM, Patterson KB, Dumond JB, et al. Pre-exposure prophylaxis for HIV prevention: how to predict success. Lancet. 2012;379: 2409-2411.
71. González de Requena D, Gallego O, De Mendoza C, et al. Indinavir plasma concentrations and resistance mutations in patients experiencing early virological failure. AIDS Res Hum Retroviruses. 2003;19:457-459.
72. Clark BM, Kotti GH, Shah AD, et al. Severe serum sickness reaction to oral and intramuscular penicillin. Pharmacotherapy. 2006;26:705-708.
73. Akkina R. New generation humanized mice for virus research: comparative aspects and future prospects. Virology. 2013;435:14-28.
74. Dezzutti CS, Hladik F. Use of human mucosal tissue to study HIV-1 pathogenesis and evaluate HIV-1 prevention modalities. Curr HIV/AIDS Rep. 2012;74:12-20.
75. Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4:151ra125.
76. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1-10.
77. Andes D, Anon J, Jacobs M, et al. Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of community-acquired respiratory tract infections. Clin Lab Med. 2004;24:477-502.
78. Barrett JS. Facilitating compound progression of antiretroviral agents via modeling and simulation. J Neuroimmune Pharmacol. 2007;2:58-71.
79. Guidi M, Arab-Alameddine M, Rotger M, et al. Dosage optimization of treatments using population pharmacokinetic modeling and simulation. CHIMIA. 2012;66:291-295.
80. Barrett JS, Labbé L, Pfister M. Application and impact of population pharmacokinetics in the assessment of antiretroviral pharmacotherapy. Clin Pharmacokinet. 2005;44:591-625.
81. Tangmunkongvorakul A, Chariyalertsak S, Amico KR, et al. Facilitators and barriers to medication adherence in an HIV prevention study among men who have sex with men in the iPrEx study in Chiang Mai, Thailand. AIDS Care. 2012 [Epub ahead of print].
82. Koenig LJ, Lyles C, Smith DK. Adherence to antiretroviral medications for HIV pre-exposure prophylaxis: lessons learned from trials and treatment studies. Am J Prev Med. 2013;44(suppl 2):S91-S98.
83. Muchomba FM, Gearing RE, Simoni JM, et al. State of the science of adherence in pre-exposure prophylaxis and microbicide trials. J Acquir Immune Defic Syndr. 2012;61:490-498.
84. Abraham BK, Gulick R. Next-generation oral preexposure prophylaxis: beyond tenofovir. Curr Opin HIV AIDS. 2012;7:600-606.
85. Mostad SB, Kreiss JK. Shedding of HIV-1 in the genital tract. AIDS. 1996;10:1305-1315.
86. Goulston C, McFarland W, Katzenstein D. Human immunodeficiency virus type 1 RNA shedding in the female genital tract. J Infect Dis. 1998;177:1100-1103.
87. Kiviat NB, Critchlow CW, Hawes SE, et al. Determinants of human immunodeficiency virus DNA and RNA shedding in the anal-rectal canal of homosexual men. J Infect Dis. 1998;177:571-578.
88. Cu-Uvin S, Caliendo a M, Reinert S, et al. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS. 2000;14: 415-421.
89. Zuckerman RA, Whittington WLH, Celum CL, et al. Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretro-viral therapy. J Infect Dis. 2004;190:156-161.
90. Cu-Uvin S, DeLong AK, Venkatesh KK, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010;24:2489-2497.
91. Neely M, Benning L, Xu J, et al. Cervical shedding of HIV-1 among women with low levels of viremia while receiving highly active antire-troviral therapy. J Acquir Immune Defic Syndr. 2011;44:38-42.
92. Chen B, Dong JQ, Pan WJ, et al. Pharmacokinetics/pharmacodynamics model-supported early drug development. Curr Pharm Biotechnol. 2012; 13:1360-1375.
93. Peck CC. Quantitative clinical pharmacology is transforming drug regulation. J Pharmacokinet Pharmacodyn. 2010;37:617-628.
94. Gibbs JP. Prediction of exposure-response relationships to support first-in-human study design. AAPS J. 2010;12:750-758.
95. Rooney KF, Snoeck E, Watson PH. Modeling and simulation in clinical drug development. Drug Discov Today. 2001;6:802-806.
96. De Ridder F. Predicting the outcome of phase III trials using phase II data: a case study of clinical trial simulation in late stage drug development. Basic Clin Pharmacol Toxicol. 2005;96:235-241.
97. Zhang L, Sinha V, Forgue ST, et al. Model-based drug development: the road to quantitative pharmacology. J Pharmacokinet Pharmacodyn. 2006;33:369-393.
98. The U.S. President's Emergency Plan for AIDS Relief. Guidance for the prevention of sexually transmitted HIV infections. Available at: http://www.pepfar.gov/documents/organization/171303.pdf. Accessed March 19, 2013.
99. World Health Organization. Guidance on couples HIV testing and counseling including antiretroviral therapy for treatment and prevention in serodiscordant couples. Available at: http://apps.who.int/iris/bitstream/10665/44646/1/ 9789241501972-eng.pdf. Accessed March 19, 2013.