HIV-1 genital shedding is suppressed in the setting of high genital antiretroviral drug concentrations throughout the menstrual cycle

Journal of Infectious Diseases

Volumn 210, Issue 5, 2014, Pages 736-744

  Sheth, Anandi N ^a   Evans Strickfaden, Tammy ^b   Haaland, Richard ^b   Martin, Amy ^b   Gatcliffe, Chelsea ^a   Adesoye, Adebola ^b   Omondi, Michael W ^b   Lupo, L Davis ^b   Danavall, Damien ^b   Easley, Kirk ^c   Chen, Cheng Yen ^b   Pau, Chou Pong ^b   Hart, Clyde ^b   Ofotokun, Igho ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

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

^c EMORY UNIVERSITY   (United States)

Author keywords

Female genital tract; HIV 1; Pharmacology; Viral shedding

Indexed keywords

ATAZANAVIR; EMTRICITABINE; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; TENOFOVIR; VIRUS DNA; VIRUS RNA;

ADULT; ANTIVIRAL THERAPY; ARTICLE; BLOOD SAMPLING; CLINICAL ARTICLE; DISEASE ASSOCIATION; DRUG EFFECT; FEMALE; FOLLICULAR PHASE; GENITAL BLEEDING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LIMIT OF QUANTITATION; LUTEAL PHASE; MENSTRUAL CYCLE; PRIORITY JOURNAL; VAGINITIS; VIRUS DETECTION; VIRUS LOAD; VIRUS REPLICATION; VIRUS SHEDDING; WOMEN'S HEALTH;

FEMALE GENITAL TRACT; HIV-1; PHARMACOLOGY; VIRAL SHEDDING;

ADENINE; ADULT; ANTI-RETROVIRAL AGENTS; DEOXYCYTIDINE; DNA, VIRAL; FEMALE; GENITALIA, FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MENSTRUAL CYCLE; MIDDLE AGED; ORGANOPHOSPHONATES; PLASMA; RITONAVIR; RNA, VIRAL; VIRAL LOAD; VIRUS SHEDDING;

EID: 84907424392     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiu166     Document Type: Article

References (40)

1. Cu-Uvin S, Caliendo AM, Reinert SE, et al. HIV-1 in the female genital tract and the effect of antiretroviral therapy. AIDS 1998; 12: 826-7.
2. 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.
3. Siegfried NL, van der Merwe L, Brocklehurst P, et al. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev 2011; 7:CD003510. DOI:003510.001002/ 14651858.CD14003510. pub14651853.
4. Hart CE, Lennox JL, Pratt-Palmore M, et al. Correlation of human immunodeficiency virus type 1 RNA levels in blood and the female genital tract. J Infect Dis 1999; 179:871-82.
5. Kovacs A, Wasserman SS, Burns D, et al. Determinants of HIV-1 shedding in the genital tract of women. Lancet 2001; 358:1593-601.
6. Coombs RW, Wright DJ, Reichelderfer PS, et al. Variation of human immunodeficiency virus type 1 viral RNA levels in the female genital tract: implications for applying measurements to individual women. J Infect Dis 2001; 184:1187-91.
7. Cu-Uvin S, Caliendo AM, Reinert S, et al. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS 2000; 14: 415-21.
8. 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; 24:2489-97.
9. Neely MN, Benning L, Xu J, et al. Cervical shedding of HIV-1 RNA among women with low levels of viremia while receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2007; 44:38-42.
10. Cu-Uvin S, Snyder B, Harwell JI, et al. Association between paired plasma and cervicovaginal lavage fluid HIV-1 RNA levels during 36 months. J Acquir Immune Defic Syndr 2006; 42:584-7.
11. Launay O, Tod M, Tschope I, et al. Residual HIV-1 RNA and HIV-1 DNA production in the genital tract reservoir of women treated with HAART: the prospective ANRS EP24 GYNODYN study. Antivir Ther 2011; 16:843-52.
12. Kelley CF, Sullivan ST, Lennox JL, et al. Lack of effect of compartmentalized drug resistance mutations on HIV-1 pol divergence in antiretroviral- experienced women. AIDS 2010; 24:1361-6.
13. Kemal KS, Foley B, Burger H, et al. HIV-1 in genital tract and plasma of women: compartmentalization of viral sequences, coreceptor usage, and glycosylation. Proc Natl Acad Sci USA 2003; 100:12972-7.
14. McClelland RS, Wang CC, Overbaugh J, et al. Association between cervical shedding of herpes simplex virus and HIV-1. AIDS 2002; 16:2425-30.
15. LeGoff J, Weiss HA, Gresenguet G, et al. Cervicovaginal HIV-1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes. AIDS 2007; 21:1569-78.
16. Johnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: a systematic review and meta-analysis. Sex Transm Dis 2008; 35:946-59.
17. Rotchford K, Strum AW, Wilkinson D. Effect of coinfection with STDs and of STD treatment on HIV shedding in genital-tract secretions: systematic review and data synthesis. Sex Transm Dis 2000; 27:243-8.
18. Cummins JE, Christensen L, Lennox JL, et al. Mucosal innate immune factors in the female genital tract are associated with vaginal HIV-1 shedding independent of plasma viral load. AIDS Res Hum Retroviruses 2006; 22:788-95.
19. Anderson BL, Wang CC, Delong AK, et al. Genital tract leukocytes and shedding of genital HIV type 1 RNA. Clin Infect Dis 2008; 47: 1216-21.
20. Benki S, Mostad SB, Richardson BA, et al. Cyclic shedding of HIV-1 RNA in cervical secretions during the menstrual cycle. J Infect Dis 2004; 189:2192-201.
21. Money DM, Arikan YY, Remple V, et al. Genital tract and plasma human immunodeficiency virus viral load throughout the menstrual cycle in women who are infected with ovulatory human immunodeficiency virus. Am J Obstet Gynecol 2003; 188:122-8.
22. Reichelderfer PS, Coombs RW, Wright DJ, et al. Effect of menstrual cycle on HIV-1 levels in the peripheral blood and genital tract. AIDS 2000; 14:2101-7.
23. Mostad SB, Jackson S, Overbaugh J, et al. Cervical and vaginal shedding of human immunodeficiency virus type 1-infected cells throughout the menstrual cycle. J Infect Dis 1998; 178:983-91.
24. Villanueva JM, Ellerbrock TV, Lennox JL, et al. The menstrual cycle does not affect human immunodeficiency virus type 1 levels in vaginal secretions. J Infect Dis 2002; 185:170-7.
25. Goulston C, Stevens E, Gallo D, et al. Human immunodeficiency virus in plasma and genital secretions during the menstrual cycle. J Infect Dis 1996; 174:858-61.
26. 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; 21:1899-907.
27. 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; 46:719-25.
28. Nettles RE, Kieffer TL, Parsons T, et al. Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring. Clin Infect Dis 2006; 42:1189-96.
29. Loutfy MR, Walmsley SL, Klein MB, et al. Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study. BMC Infect Dis 2013; 13:256.
30. Kashuba AD, Nafziger AN. Physiological changes during the menstrual cycle and their effects on the pharmacokinetics and pharmacodynamics of drugs. Clin Pharmacokinet 1998; 34:203-18.
31. Dumond JB, Nicol MR, Kendrick RN, et al. Pharmacokinetic modelling of efavirenz, atazanavir, lamivudine and tenofovir in the female genital tract of HIV-infected pre-menopausal women. Clin Pharmacokinet 2012; 51:809-22.
32. Kuklenyik Z, Martin A, Pau CP, et al. Effect of mobile phase pH and organic content on LC-MS analysis of nucleoside and nucleotide HIV reverse transcriptase inhibitors. J Chromatogr Sci 2009; 47:365-72.
33. Diggle PJ, Liang KY, Zeger SL. Analysis of Longitudinal Data. Oxford: Clarendon Press, 1994: 68.
34. Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986; 42:121-30.
35. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. http:// aidsinfo.nih.gov/ContentFiles/ AdultandAdolescentGL.pdf. Accessed 20 November 2013.
36. Moreira C, Venkatesh KK, DeLong A, et al. Effect of treatment of asymptomatic bacterial vaginosis on HIV-1 shedding in the genital tract among women on antiretroviral therapy: a pilot study. Clin Infect Dis 2009; 49:991-2.
37. Baeten JM, Kahle E, Lingappa JR, et al. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci Transl Med 2011; 3:77ra29.
38. 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.
39. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367:423-34.
40. Salle B, Brochard P, Bourry O, et al. Infection of macaques after vaginal exposure to cell-associated simian immunodeficiency virus. J Infect Dis 2010; 202:337-44.