Youth-specific considerations in the development of preexposure prophylaxis, microbicide, and vaccine research trials

Journal of Acquired Immune Deficiency Syndromes

Volumn 54, Issue SUPPL. 1, 2010, Pages

  Rudy, Bret J ^a   Kapogiannis, Bill G ^b   Lally, Michelle A ^c   Gray, Glenda E ^d   Bekker, Linda Gail ^e   Krogstad, Paul ^f   McGowan, Ian ^g  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^c BROWN UNIVERSITY   (United States)

^d UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^e UNIVERSITY OF CAPE TOWN   (South Africa)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

adolescents; biomedical HIV prevention; microbicides; PrEP; vaccines; youth

Indexed keywords

ADENOVIRUS TYPE 5 VECTOR VACCINE; DAPIVIRINE; EMTRICITABINE; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; MICROBICIDE; RECOMBINANT CANARYPOX VACCINE; RILPIVIRINE; TENOFOVIR DISOPROXIL; UNCLASSIFIED DRUG; VIVAGEL;

CHEMOPROPHYLAXIS; CLINICAL TRIAL; DRUG EFFICACY; DRUG REEXPOSURE; DRUG SAFETY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOPROPHYLAXIS; INFECTION PREVENTION; INTERVENTION STUDY; MEDICAL TECHNOLOGY; NEPHROTOXICITY; PREVENTIVE MEDICINE; PRIORITY JOURNAL; REVIEW;

ADMINISTRATION, INTRAVAGINAL; ADMINISTRATION, RECTAL; ADOLESCENT; AGE FACTORS; AIDS VACCINES; ANTI-HIV AGENTS; ANTI-INFECTIVE AGENTS, LOCAL; CLINICAL TRIALS AS TOPIC; FEMALE; HIV INFECTIONS; HIV SEROPOSITIVITY; HUMANS; MALE;

EID: 77954064076     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAI.0b013e3181e3a922     Document Type: Review

References (93)

1. Slap GB. Normal physiological and psychosocial growth in the adolescent. J Adolesc Health Care. 1986;7:13S-23S.
2. Stirratt MJ, Gordon CM. Adherence to biomedical HIV prevention methods: considerations drawn from HIV treatment adherence research. Curr HIV/AIDS Rep. 2008;5:186-1192.
3. Rudy BJ, Lindsey JC, Flynn, PM, et al. Immune reconstitution and predictors of virologic failure in adolescents infected through risk behaviors and initiating HAART: week 60 results from the PACTG 381 cohort. AIDS Res Hum Retroviruses. 2006;22:213-221.
4. Guest G, Shattuck D, Johnson L, et al. Changes in sexual risk behavior among participants in a PrEP HIV prevention trial. Sex Transm Dis. 2008; 35:1002-1008.
5. Allen M, Israel H, Rybczyk K, et al. Trial-related discrimination in HIV vaccine clinical trials. AIDS Res Hum Retroviruses. 2001;17:667-674.
6. Allen M, Metch B, Lau C, et al. Negative social impacts in preventive HIV vaccine clinical trials [abstract OA06-02]. Presented at: AIDS Vaccine; August 29-September 1; Amsterdam, Netherlands. 2006.
7. HIV Vaccine Trials Network: Participants' Bill of Rights and Responsibilities. Available at: http://www.hvtn.org/community/rights.html. Accessed April 3, 2010.
8. Rogol AD, Roemmich JN, Clark PA. Growth at puberty. J Adolesc Health. 2002;31:192-200.
9. Hoody DW, Fletcher CV. Pharmacology considerations for antiretroviral therapy in human immunodeficiency virus (HIV)-infected children. Semin Pediatr Infect Dis. 2003;14:286-294.
10. Lee V, Tobin JM, Foley E. Relationship of cervical ectopy to Chlamydia infection in young women. J Fam Plann Reprod Health Care. 2006;32: 104-106.
11. Monroy OL, Aguilar C, Lizano M, et al. Prevalence of human papillomavirus genotypes, and mucosal IgA anti-viral responses in women with cervical ectopy. J Clin Virol. 47:43-48.
12. Peterson L, Taylor D, Roddy R, et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials. 2007;2:e27.
13. Fauci AS, Johnston MI, Dieffenbach CW, et al. HIV vaccine research: the way forward. Science. 2008;321:530-532.
14. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209-2220.
15. Tsai CC, Follis KE, Sabo A, et al. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science. 1995; 270:1197-1199.
16. Rosenwirth B, ten Haaft P, Bogers WM, et al. Antiretroviral therapy during primary immunodeficiency virus infection can induce persistent suppression of virus load and protection from heterologous challenge in rhesus macaques. J Virol. 2000;74:1704-1711.
17. Connor EM, Mofenson LM. Zidovudine for the reduction of perinatal human immunodeficiency virus transmission: pediatric AIDS Clinical Trials Group Protocol 076\results and treatment recommendations. Pediatr Infect Dis J. 1995;14:536-541.
18. Volmink J, Siegfried NL, van der Merwe L, et al. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2007;CD003510.
19. Garcia-Lerma JG, Otten RA, Qari SH, et al. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med. 2008;5:e28.
20. Garcia-Lerma JG, Paxton L, Kilmarx PH, et al. Oral pre-exposure prophylaxis for HIV prevention. Trends Pharmacol Sci. 31:74-81.
21. Gilead Sciences. Truvada (tenofovir disoproxil fumarate and emtricitabine) tablets [product information]. 2010. http://www,gilead.com/pdf. truvada.
22. Palacios R, Hidalgo C, Rios MJ, et al. Effectiveness and safety of simplification from tenofovir-lamivudine (TDF-3TC) to tenofovir-emtricitabine (TDF-FTC) co-formulation (Truvada) in virologically suppressed HIV-infected patients on HAART. Eur J Clin Microbiol Infect Dis. 2009;28: 399-402.
23. Khokhar A, Afdhal NH. Therapeutic strategies for chronic hepatitis B virus infection in 2008. Am J Med. 2008;121:S33-S44.
24. Adusumilli S. Tenofovir disoproxil fumarate for the treatment of hepatitis B infection. Drugs Today (Barc). 2009;45:679-685.
25. Dore GJ, Soriano V, Rockstroh J, et al. Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption. AIDS. 24:857-865.
26. Calmy A, Fux CA, Norris R, et al. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis 2009;200:1746-1754.
27. Riordan A, Judd A, Boyd K, et al. Tenofovir use in human immunodeficiency virus-1-infected children in the United Kingdom and Ireland. Pediatr Infect Dis J. 2009;28:204-209.
28. Vigano A, Zuccotti GV, Martelli L, et al. Renal safety of tenofovir in HIV-infected children: a prospective, 96-week longitudinal study. Clin Drug Investig. 2007;27:573-581.
29. Pozniak AL, Morales-Ramirez J, Katabira E, et al. Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial. AIDS. 2010;24:55-65.
30. Eron JJ Jr. Antiretroviral therapy: new drugs, formulations, ideas, and strategies. Top HIV Med. 2009;17:146-150.
31. Pre-Exposure Prophylaxis in YMSM. Available at: http://clinicaltrials. gov/ct2/show/NCT01033942. Accessed March 29, 2010.
32. McGowan I. Microbicides: a new frontier in HIV prevention. Biologicals. 2006;34:241-255.
33. McGowan I. Microbicides for HIV prevention: reality or hope? Curr Opin Infect Dis. 23:26-31.
34. Cummins JE Jr, Doncel GF. Biomarkers of cervicovaginal inflammation for the assessment of microbicide safety. Sex Transm Dis. 2009;36: S84-S91.
35. Poynten IM, Millwood IY, Falster MO, et al. The safety of candidate vaginal microbicides since nonoxynol-9: a systematic review of published studies. AIDS. 2009;23:1245-1254.
36. Hendrix CW, Cao YJ, Fuchs EJ. Topical microbicides to prevent HIV: clinical drug development challenges. Annu Rev Pharmacol Toxicol. 2009;49:349-375.
37. 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.
38. Dumond JB, Patterson KB, Pecha AL, et al. Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative women. J Acquir Immune Defic Syndr. 2009;51:546-553.
39. Feldblum PJ, Adeiga A, Bakare R, et al. SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria. PLoS One. 2008;3:e1474
40. Halpern V, Ogunsola F, Obunge O, et al. Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria. PLoS One. 2008;3:e3784
41. Peterson L, Nanda K, Opoku BK, et al. SAVVY (C31G) gel for prevention of HIV infection in women: a phase 3, double-blind, randomized, placebo-controlled trial in Ghana. PLoS One. 2007;2:e1312
42. Skoler-Karpoff S, Ramjee G, Ahmed K, et al. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1977-1987.
43. Van Damme L, Govinden R, Mirembe FM, et al. Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission. N Engl J Med. 2008;359:463-472.
44. Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet. 2002;360:971-977.
45. Grant RM, Hamer D, Hope T, et al. Whither or wither microbicides? Science. 2008;321:532-534.
46. Leynaert B, Downs AM, de Vincenzi I. Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV. Am J Epidemiol. 1998;148:88-96.
47. Vittinghoff E, Douglas J, Judson F, et al. Per-contact risk of human immunodeficiency virus transmission between male sexual partners. Am J Epidemiol. 1999;150:306-311.
48. Gorbach PM, Manhart LE, Hess KL, et al. Anal intercourse among young heterosexuals in three sexually transmitted disease clinics in the United States. Sex Transm Dis. 2009;36:193-198.
49. Kalichman SC, Simbayi LC, Cain D, et al. Heterosexual anal intercourse among community and clinical settings in Cape Town, South Africa. Sex Transm Infect. 2009;85:411-415.
50. Baral S, Trapence G, Motimedi F, et al. HIV prevalence, risks for HIV infection, and human rights among men who have sex with men (MSM) in Malawi, Namibia, and Botswana. PLoS One. 2009;4:e4997
51. McGowan I. Rectal microbicides: a new focus for HIV prevention. Sex Transm Infect. 2008;84:413-417.
52. Anton P, Adler A, Khanukova E, et al.A phase 1 rectal safety and acceptability study of UC781 microbicide gel. Presented at: 16th Conference on Retroviruses and Opportunistic Infections; 2009. February 9, 2009; Montreal, Canada.
53. McGowan I, Elliott J, Cortina G, et al. Characterization of baseline intestinal mucosal indices of injury and inflammation in men for use in rectal microbicide trials (HIV Prevention Trials Network-056). J Acquir Immune Defic Syndr. 2007;46:417-425.
54. Hendrix CW, Fuchs EJ, Macura KJ, et al. Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates. Clin Pharmacol Ther. 2008;83:97-105.
55. Carballo-Dieguez A, Dolezal C, Bauermeister JA, et al. Preference for gel over suppository as delivery vehicle for a rectal microbicide: results of a randomised, crossover acceptability trial among men who have sex with men. Sex Transm Infect. 2008;84:483-487.
56. Ventuneac A, Carballo-Dieguez A, McGowan I, et al. Acceptability of UC781 gel as a rectal microbicide among HIV-uninfected women and men. AIDS Behav. 2010;14:618-628.
57. Short MB, Succop PA, Rupp R, et al. Adolescents' reasons for using a microbicide-like product over time. Int J STD AIDS. 2008;19: 115-117.
58. Short MB, Rosenthal SL, Auslander BA, et al. Relationship context associated with microbicide-like product use. J Pediatr Adolesc Gynecol. 2009;22:313-317.
59. Lewis, D, Tu W. The Physiological immundeficiency of immaturity. In: Immunologic Disorders in Infants and Children. Stiehm EW, JA, eds. Philadelphia, PA: Elsevier-Saunders; 2004. pp. 687-760
60. Lewinsohn DA, Gennaro ML, Scholvinck L, et al. Tuberculosis immunology in children: diagnostic and therapeutic challenges and opportunities. Int J Tuberc Lung Dis. 2004;8:658-674.
61. Lewinsohn DA, Lewinsohn DM. Immunologic susceptibility of young children to Mycobacterium tuberculosis. Pediatr Res. 2008;63:115.
62. Bradley S. Infections. In: Practice of Geriatrics. Duthie EH, Katz PR, Malone M, eds. Philadephia, PA: Elsevier Saunders; 2007. pp. 410-420.
63. Edwards MS, Baker CJ. Group B streptococcal infections in elderly adults. Clin Infect Dis. 2005;41:839-847.
64. Arvin A. Aging, immunity, and the varicella-zoster virus. N Engl J Med. 2005;352:2266-2267.
65. Dorshkind K, Swain S. Age-associated declines in immune system development and function: causes, consequences, and reversal. Curr Opin Immunol. 2009;21:404-407.
66. Kollman C, Howe, CW, Anasetti C, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001;98:2043-2051.
67. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396: 690-695.
68. Harris JM, Hazenberg MD, Poulin, JF, et al. Multiparameter evaluation of human thymic function: interpretations and caveats. Clin Immunol. 2005; 115:138-146.
69. Haynes BF, Markert ML, Sempowski GD, et al. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol. 2000;18:529-560.
70. Lee JC, Boechat MI, Belzer M, et al. Thymic volume, T-cell populations, and parameters of thymopoiesis in adolescent and adult survivors of HIV infection acquired in infancy. AIDS. 2006;20:667-674.
71. Jamieson BD, Douek DC, Killian S, et al. Generation of functional thymocytes in the human adult. Immunity. 1999;10:569-575.
72. Effros RB. Role of T lymphocyte replicative senescence in vaccine efficacy. Vaccine. 2007;25:599-604.
73. Naylor K, Li G, Vallejo AN, et al. The influence of age on T cell generation and TCR diversity. J Immunol. 2005;174:7446-7452.
74. Mackall CL, Fleisher TA, Brown MR, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med. 1995;332:143-149.
75. Hakim FT, Memon SA, Cepeda R, et al. Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest. 2005; 115:930-939.
76. Resino S, Galan I, Perez A, et al. HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy. Clin Exp Immunol. 2004;137:570-577. (Pubitemid 39128085)
77. Sleasman JW, Nelson RP, Goodenow MM, et al. Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages. J Pediatr. 1999;134: 597-606.
78. van Rossum AM, Scherpbier HJ, van Lochem EG, et al. Therapeutic immune reconstitution in HIV-1-infected children is independent of their age and pretreatment immune status. AIDS. 2001;15:2267-2275.
79. Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997;277:112-116.
80. Pakker NG, Kroon ED, Roos MT, et al. Immune restoration does not invariably occur following long-term HIV-1 suppression during antire-troviral therapy. INCAS Study Group. AIDS. 1999;13:203-212.
81. Micheloud D, Berenguer J, Bellon JM, et al. Negative influence of age on CD4+ cell recovery after highly active antiretroviral therapy in naive HIV-1-infected patients with severe immunodeficiency. J Infect. 2008;56:130-136.
82. Clute SC, Watkin LB, Cornberg M, et al. Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. J Clin Invest. 2005;115:3602-3612.
83. Cornberg M, Chen AT, Wilkinson LA, et al. Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity. J Clin Invest. 2006;116:1443-1456.
84. White CJ, Kuter BJ, Hildebrand CS, et al. Varicella vaccine (VARIVAX) in healthy children and adolescents: results from clinical trials, 1987 to 1989. Pediatrics. 1991;87:604-610.
85. Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent Human Papillomavirus Vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56:1-24.
86. Skowronski DM, Tweed SA, De Serres G. Rapid decline of influenza vaccine-induced antibody in the elderly: is it real, or is it relevant? J Infect Dis. 2008;197:490-502.
87. Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191:654-665.
88. Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006;194:1661-1671.
89. Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372: 1881-1893.
90. Gray G, Allen M, Churchyard G, et al. A multicenter double-blind randomized placebo-controlled phase IIB test-of-concept study to evaluate the safety and efficacy of a 3-dose regimen of the Clade B-based Merck Adenovirus serotype 5 HIV-1 gag/pol/nef vaccine in HIV-1-uninfected adults in South Africa [SS01-04]. Presented at: AIDS Vaccine; October 20, 2009; Paris, France.
91. US Food and Drug Administration (2006). Guidance for industry: development of preventive HIV vaccines for use in pediatric populations. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm 092165.pdf. Accessed April 5, 2010.
92. Bartholow BN, Buchbinder S, Celum C, et al. HIV sexual risk behavior over 36 months of follow-up in the world's first HIV vaccine efficacy trial. J Acquir Immune Defic Syndr. 2005;39:90-101.
93. Padian NS, Buve A, Balkus J, et al. Biomedical interventions to prevent HIV infection: evidence, challenges, and way forward. Lancet. 2008;372: 585-599.