Sexually Transmitted Infections

Effect of Lactobacillus on Genital HIV-1 RNA and DNA Shedding in Women

Jane E Hitti, MD, MPH

Genital HIV-1 viral load is a major predictor of sexual and perinatal HIV transmission, and strategies to decrease HIV-1 shedding, while promoting vaginal health, are urgently needed. We hypothesize that hydrogen peroxide-producing lactobacillus (L. crispatus and L. jensenii), key components of the normal vaginal flora, decrease genital HIV-1 RNA and DNA shedding among HIV-1-infected women by direct viral inhibition and also by relative suppression of potentially pathogenic vaginal bacteria associated with bacterial vaginosis (BV). We propose to evaluate this hypothesis using archived cervicovaginal lavage (CVL) and cervical cytobrush samples from parallel cohorts of HIV-1-infected women in the United States and Kenya. Specifically, we will:

  1. Examine the effect over time of L. crispatus, L. jensenii, and L. iners presence and concentrations on HIV-1 RNA load in CVL, as well as the effect of these organisms on pro-inflammatory cytokines and other BV-associated flora. We anticipate that acquisition and/or higher concentrations of L. crispatus and L. jensenii (but not L. iners) will result in a signifi cant decrease in CVL HIV-1 RNA accounting for other factors such as plasma viral load and antiretroviral therapy, and that this protective effect may be mediated by down-regulation of pro-inflammatory cytokines and/or suppression of BV-associated bacteria.
  2. Assess the longitudinal effect of vaginal Lactobacillus species, other BV-associated organisms, and pro-inflammatory cytokines on endocervical HIV-1 DNA quantitation, as well as endocervical HIV-1 RNA. We hypothesize that the protective effect of L. crispatus and L. jensenii will extend to the endocervix and will include a decrease in proliferation of HIV-1-infected cells as well as viral replication.

Taken together, these aims will add to our understanding of the mechanisms by which hydrogen peroxide-producing lactobacillus modulates HIV-1 in the female genital tract, and may add rationale for further evaluation of probiotics as a potential secondary HIV-1 prevention strategy.

Funding Source: NIH
Contact: Jane E Hitti, MD, MPH, (206) 543-9867
Ends 8/31/2011

UW IMPAACT Clinical Trial Unit

Jane E Hitti, MD, MPH

The Seattle Children's Hospital/University of Washington International Maternal, Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) site is the only perinatal/pediatric clinical trials unit in the Pacific Northwest, and offers treatment trials to all HIV-infected pregnant women and HIV-exposed or infected children in the region. These funds support the screening, enrollment, and follow-up of HIV-infected pregnant and postpartum women and their HIV-exposed infants into clinical trials in the IMPAACT network, with attention to providing excellent quality of data collection and timeliness.

Funding Source: Seattle Children's Hospital/Research
Contact: Jane E Hitti, MD, MPH, (206) 543-9867
Ends 11/30/10

HIV-Specific Antibodies in Vaginal Swabs from HIV-Uninfected HPTN-035 Participants

Florian Hladik, MD, PhD

HPTN 035 is a phase II/IIb safety and effectiveness study of the vaginal microbicides buffer gel and 0.5% PRO 2000/5 gel for the prevention of HIV infection in women. This study will address the hypothesis that women sexually exposed to HIV-1 (while using a topical microbicide) and who remain uninfected develop a compartmentalized humoral immune response.

Secretions extracted from vaginal swabs will be tested for HIV-specific IgG and IgA antibodies by luminex technology. These assays will be performed in collaboration with Dr. Georgia Tomaras (Duke University, NC). We will initially screen swabs from 100 HIV-uninfected and 10 HIV-infected women (positive controls). The luminex technology enables multiplexed quantification of both IgG and IgA antibodies directed at HIV-1 clade C consensus sequence antigens, including Env gp120, Env gp41, Gag and accessory proteins. Based on the initial results with 100 HIV-uninfected women, we will continue to screen a larger cohort of HPTN 035 participants.

Funding Source: Magee-Womens Research Institute and Foundation
Contact: Florian Hladik, MD, PhD, (206) 221-2740
Ends 4/30/2011

A Randomized, International, Double-Blind, Controlled with GARDASIL TM, Dose-Ranging, Tolerability, Immunogenicity, and Efficacy Study of a Second Generation Human Papillomavirus L1 Virus-Like Particle Vaccine Administered to 16 to 26 Year Old Women

Constance Mao, MD

Funding Source:
Contact: Constance Mao, MD, (206) 744-6291
Ends 10/31/2011

Safety and Efficacy of Chlamydia Vaccine Candidates

Dorothy Patton, PhD

Funding Source: Wyeth Pharmaceuticals
Contact: Dorothy L Patton, PhD, (206) 543-5554
Ends 4/29/2012