Genital Tenofovir Concentrations Correlate with Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness

Journal of Acquired Immune Deficiency Syndromes

Volumn 69, Issue 3, 2015, Pages 264-269

  Kashuba, Angela D M ^a   Gengiah, Tanuja N ^b   Werner, Lise ^b   Yang, Kuo Hsiung ^a   White, Nicole R ^a   Karim, Quarraisha A ^a,c   Abdool Karim, Salim S ^a,c  

^a UNC Hamner Institute for Drug Safety Sciences   (United States)

^b UNIVERSITY OF KWAZULU NATAL   (South Africa)

^c Department of Medicine   (United States)

Author keywords

adherence; genital tract; HIV; protection; tenofovir

Indexed keywords

ANTIRETROVIRUS AGENT; PLACEBO; TENOFOVIR; TENOFOVIR DIPHOSPHATE; UNCLASSIFIED DRUG; ADENINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; GEL; PHOSPHONIC ACID DERIVATIVE;

ADULT; ARTICLE; CERVICOVAGINAL FLUID; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; CORRELATION COEFFICIENT; DIAGNOSTIC TEST ACCURACY STUDY; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG EFFICACY; FEMALE; GEL; GENITAL SYSTEM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION PREVENTION; MAXIMUM PLASMA CONCENTRATION; MEDICATION COMPLIANCE; PATIENT COMPLIANCE; PATIENT SELECTION; PHARMACODYNAMICS; PLASMA; PREDICTIVE VALUE; PRIORITY JOURNAL; SEROCONVERSION; UTERINE CERVIX; VAGINA; VAGINA DISCHARGE; YOUNG ADULT; ANALOGS AND DERIVATIVES; CASE CONTROL STUDY; HIV INFECTIONS; METABOLISM; RANDOMIZED CONTROLLED TRIAL; SOUTH AFRICA; TISSUE DISTRIBUTION;

ADENINE; ADULT; ANTI-HIV AGENTS; CASE-CONTROL STUDIES; CERVIX UTERI; FEMALE; GELS; HIV INFECTIONS; HUMANS; MEDICATION ADHERENCE; ORGANOPHOSPHONATES; SOUTH AFRICA; TENOFOVIR; TISSUE DISTRIBUTION; VAGINA; YOUNG ADULT;

EID: 84933047153     PISSN: 15254135     EISSN: 10779450     Source Type: Journal    
DOI: 10.1097/QAI.0000000000000607     Document Type: Article

References (23)

1. UNAIDS. The Gap Report. 2014. Available at: http://www.who.int/tb/ publications/global-report/en/. Accessed September 1, 2014.
2. Padian NS, Buve A, Balkus J, et al. Biomedical interventions to prevent HIV infection: evidence, challenges, and way forward. Lancet. 2008;372: 585-599.
3. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367: 399-410.
4. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381:2083-2090.
5. 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.
6. 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;329:1168-1174.
7. Abdool Karim SS; on behalf of the CAPRISA 004 Trial Group. CAPRISA 004: effectiveness and safety of vaginal microbicide 1% tenofovir gel for prevention of HIV infection in women: Paper presented at: XVIII International AIDS Conference; July 18-23, 2010; Vienna, Austria.
8. Karim SS, Kashuba AD, 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.
9. 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 emtricitabine. J Virol. 2009;83:10358-10365.
10. Denton PW, Othieno F, Martinez-Torres F, et al. One percent tenofovir applied topically to humanized BLT mice and used according to the CAPRISA 004 experimental design demonstrates partial protection from vaginal HIV infection, validating the BLT model for evaluation of new microbicide candidates. J Virol. 2011;85:7582-7593.
11. Karim QA, Kharsany AB, Frohlich JA, et al. Stabilizing HIV prevalence masks high HIV incidence rates amongst rural and urban women in KwaZulu-Natal, South Africa. Int J Epidemiol. 2011;40:922-930.
12. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.
13. 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. 2011;3:112re114.
14. Marrazzo J, Ramjee G, Nair G, et al VOICE Study Team. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir gel in the voice study (MTN003). Conference of Retroviral and Opportunistic Infections, Georgia World Congress Centre; March 3-6, 2013; Atlanta, GA. Abstract#26LB.
15. Hendrix CW, Chen BA, Guddera V, et al. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PloS One. 2013;8:e55013.
16. Sokal DC, Karim QA, Sibeko S, et al. Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial. Antivir Ther. 2013;18:301-310.
17. Dobard C, Sharma S, Martin A, et al. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue. J Virol. 2012;86:718-725.
18. 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.
19. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. The New England journal of medicine. 2012;367(5):423-434.
20. 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.
21. Berg KM, Arnsten JH. Practical and conceptual challenges in measuring antiretroviral adherence. J Acquir Immune Defic Syndr. 2006;43(suppl 1): S79-S87.
22. Amico KR, Liu A, McMahan V, et al. Adherence Indicators and pre-exposure prophylaxis (PrEP) drug levels in the iPrEx study. Paper presented at: Conference on Retroviruses and Opportunistic Infections; 2011; Boston, MA.
23. Yang KH, Schwartz JL, Sykes C, Doncel GF, et al. Population pharmacokinetic model of vaginal tenofovir 1% gel in the cervicovaginal fluid. HIV research for prevention; February 28-March 2, 2011; Cape Town, South Africa. Abstract# OA13.04.