Darron Brown

Publications (5)17.92 Total impact

• Article: Reduction of HPV infections through vaccination among at-risk urban adolescents.

  Teresa Cummings, Gregory D Zimet, Darron Brown, Wanzhu Tu, Ziyi Yang, J Dennis Fortenberry, Marcia L Shew
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  ABSTRACT: Human papillomavirus (HPV) vaccine trials have demonstrated high efficacy in preventing HPV infections and HPV related disease in females ages 16-26. However, there is no source data to demonstrate the impact of the vaccine in other populations who may be at higher risk for HPV related disease. This study examines the impact of HPV vaccination on subsequent HPV detection and sexual behaviors among urban adolescents in a clinical setting. A cohort of adolescent women, ages 14-17, were recruited prospectively and matched to historical controls to assess the impact of HPV vaccination. All women completed the same questionnaire and face-to-face interview that assessed sexual behaviors; all provided a clinician or self-collected vaginal swab that was used to test for sexually transmitted infections, including HPV. Logistic regression models, incorporating random pair effects, were used to assess the impact of the HPV vaccine on HPV detection and sexual behaviors between the two groups. Each woman recruited (N=75) was matched to 2 historical controls (HC); most of the recruited women (89.3%) had received one or more doses of the HPV vaccine. At enrollment, detection of quadrivalent vaccine types (HPV 6, 11, 16 and 18) was significantly less in the recruited group (5.3%) as compared to the HC (24%): OR=5.6 (CI=1.9, 16.5), p=0.002. Adolescent women in the HC had a 9.5 times greater odds of HPV infection when the analysis was adjusted to compare those who had 2 or more vaccine doses to their matched controls. The only behavioral difference found was that the recruited women used condoms more frequently. This study demonstrates that HPV vaccination was associated with fewer vaccine-type HPV infections despite incomplete vaccination and high risk sexual behaviors. These data also suggest that sexual behaviors were not altered because of the vaccine.
  Vaccine 06/2012; 30(37):5496-9. · 3.77 Impact Factor
• Article: Natural history of multiple human papillomavirus infections in female adolescents with prolonged follow-up.

  Bree Weaver, Marcia Shew, Brahim Qadadri, Wanzhu Tu, Yan Tong, Cheryl Denski, J Dennis Fortenberry, Darron Brown
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  ABSTRACT: The aim of the study was to better characterize the natural history of human papillomavirus (HPV) infections in female adolescents. Female adolescents were enrolled in a longitudinal study. Self-vaginal samples were obtained every 3 months and tested for HPV. No participants received HPV vaccination. The findings for 40 female adolescents with the longest follow-up are reported in this study. Average age at the time of enrollment was 15.2 years (range: 14-17; SD: .97). Mean duration of follow-up was 6.7 years (range: 4.4-9.2; SD: 1.2). In all, 32 participants (80%) reported being involved in sexual activity before their enrollment in the study; all reported being involved in sexual activity before enrollment; all reported being involved in sexual activity during follow-up. Baseline and cumulative prevalence of HPV among participants was 55% and 100%, respectively. During the study, each participant tested positive for a mean of 14 HPV types. Cumulatively, HPV 16 was detected in 29 of 40 participants (72.5%). Mean duration of high- and low-risk infections was 655.9 (median: 433) and 524.1 days (median: 334), respectively. With prolonged follow-up, HPV infections with multiple types were found in all participants. Most had infection with HPV-16 or HPV-18, the oncogenic types represented in current vaccines, as well as infection with other oncogenic types. These data reinforce the importance of vaccine and non-vaccine strategies for prevention of HPV infections.
  Journal of Adolescent Health 05/2011; 48(5):473-80. · 3.33 Impact Factor
• Article: Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.

  Sven-Eric Olsson, Susanne K Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Cosette M Wheeler, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, [......], Frank J Taddeo, Christine Roberts, Amha Tadesse, Janine Bryan, Roger Maansson, Scott Vuocolo, Teresa M Hesley, Alfred Saah, Eliav Barr, Richard M Haupt
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  ABSTRACT: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. 18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >or=1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment. These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
  Human vaccines 10/2009; 5(10):696-704. · 3.58 Impact Factor
• Article: Prevalence and persistence of cervical human papillomavirus infection in HIV-positive women initiating highly active antiretroviral therapy.

  Kenneth H Fife, Julia W Wu, Kathleen E Squires, D Heather Watts, Janet W Andersen, Darron R Brown
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  ABSTRACT: To determine the prevalence of human papillomavirus (HPV) DNA in cervical specimens from treatment-naive women initiating highly active antiretroviral therapy (HAART) and explore the longitudinal association of HPV DNA with CD4 count and HIV viral load (VL). Women enrolled before HAART were evaluated at baseline, weeks 24, 48, and 96 with CD4 count, VL, and cervical swab for HPV DNA. The 146 subjects had a median CD4 count of 238 cells per microliter and VL of 13,894 copies per milliliter. Ninety-seven subjects (66%) had HPV DNA detected in the baseline specimen including 90 subjects (62%) positive for 1 or more high-risk HPV types. HPV DNA detection declined to 49% at week 96 and that of a high risk HPV type to 39%. The duration of follow-up was associated with decreased detection of HPV DNA of any type (P = 0.045) and of high-risk HPV types (P = 0.003). There was at most a marginal association between HAART response and loss of detection of cervical HPV DNA. Women initiating HAART had a high prevalence of cervical HPV DNA that declined over 96 weeks of HAART. The relationship of CD4 count and VL response to the decline of cervical HPV DNA was not strong.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2009; 51(3):274-82. · 4.43 Impact Factor
• Article: Infection with Human Papillomavirus alters expression of the small proline rich proteins 2 and 3.

  Elizabeth Lehr, Daniel Hohl, Marcel Huber, Darron Brown
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  ABSTRACT: Human papillomavirus (HPV) does not induce lysis of infected keratinocytes, and the exact mechanisms of viral escape are not known. As keratinocytes differentiate, the cornified cell envelope (CCE) develops, providing a protective barrier to the host. Our prior studies have identified abnormalities in CCEs isolated from genital epithelium infected with HPV 11 (a low-risk HPV type) and HPV 59 (a high-risk HPV type). These abnormalities included reduced thickness and increased fragility compared to CCEs in healthy epithelium. Transcription of loricrin is also reduced in HPV 11- and 59-infected epithelium. In this study, uninfected and HPV 11- or 59-infected human genital epithelium were examined for expression of the small proline rich proteins (SPRs), which serve as cross-linking proteins within the CCE. Limiting cycle RT-PCR was performed to detect the various SPR transcripts in HPV 11- and 59-infected, or uninfected epithelium. Immunohistochemical analysis and immunoblot assays were performed to analyze the distribution and quantity of SPR2A, SPR2B, and SPR3. SPR2B transcripts were moderately increased in the HPV 11- and 59-infected tissues and SPR3 transcripts were significantly increased in HPV 11-infected tissues and minimally increased in HPV 59-infected tissues. SPR2B protein quantities were moderately increased while SPR2A was not significantly changed. SPR3 protein, while not present in uninfected epithelium, was detected in abundance in HPV 11-infected tissue. We conclude that low-risk and high-risk HPVs share the ability to alter expression of CCE proteins, although the exact mechanisms may differ. Expression of individual SPRs differed between these types and these alterations may play a role in fragility of CCEs in HPV infection.
  Journal of Medical Virology 04/2004; 72(3):478-83. · 2.82 Impact Factor