Multipurpose Prevention Technologies (MPT)

UW IMPAACT Clinical Trial Unit (Year 7)

Jane E Hitti, MD, MPH, Principal Investigator

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
End Date: 11-30-2017

Ryan White Part D Services

Jane E Hitti, MD, MPH, Principal Investigator

As part of the Department of Health, Washington State, effort to provide leadership and quality assurance for its perinatal and obstetrical services, the DOH is contracting with the University of Washington School of Medicine, Department of Obstetrics and Gynecology for nurse midwife services. The DOH will contract for Barbara Baker and TBD-Nurse Coordinator with the following objective: Reduce perinatal transmission of HIV+ through the provision of medical services to HIV+ pregnant women and follow-up to perinatally-exposed infants.

Funding Source: Washington State Department of Health (DOH)/
Health Resources and Services Administration (HRSA)
End Date: 7-31-17

HIV Vaccine Trials Network (HVTN) Laboratory Program

Florian Hladik, MD, PhD, Investigator (PI: McElrath MJ)

The overall goal of the HVTN laboratory program is to conduct through the HIV Trials Network high quality, state-of-the art, laboratory-based clinical research and evaluation that leads to the development of a safe and efficacious HIV vaccine.

Funding Source: NIH/NIAID
End Date: 11-30-20

Center for AIDS Research (CFAR). Core I: Immunology (Co-Directors: De Rosa & Stamatatos)

Florian Hladik, MD, PhD, Investigator (PI: King Holmes)

The Center for AIDS Research (CFAR) Imunology Core will offer all CFAR investigators innovative new and cutting-edge technologies (e.g., CyTOF, digital droplet PCR, single cell analysis technologies) to assess molecular and cellular immune phenotypes and functions in diverse tissue types. Dr. Hladik will provide expertise on mucosal immunology.

Funding Source: NIH/NIAID
End Date: 5-31-18

Clinical Epidemiology and Pathogenesis of Asymptomatic HSV Infection
Project 1: Incident HSV-2 and Genital Health in Kenyan Adolescent Girls: An Inception Cohort

Florian Hladik, MD, PhD, Co-Investigator/Project 1 Leader (PI: Anna Wald, MD, MPH)

Herpes simplex virus type 2 (HSV-2) infections are one of the driving forces behind the HIV epidemic in sub-Saharan Africa. This is especially true for adolescent/young women who acquire both infections rapidly after sexual debut. We hypothesize that genital inflammation among young women in sub-Saharan Africa is largely driven by HSV-2 acquisition. Our Specific Aim 1 will determine if HSV-2 acquisition among young African women results in persistent (>1 year) genital inflammation. The primary outcome will be the change in concentrations of the three pro-inflammatory factors MIP-1ß, IL-1 and IL-8, measured by Luminex assays in cervicovaginal lavage (CVL) samples from adolescent women before and after initiation of sexual activity, and after HSV-2 seroconversion. We will test for other sexually transmitted infections, and for sexual activity by PSA, to determine their relative contribution to genital inflammation.
A secondary clinical outcome will be the density of vulvar infiltration with HIV target cells, as measured by absolute densities of CCR5+ T cells, macrophages and dendritic cells (DCs), quantified by immunofluorescence staining vulvar biopsies obtained from women before and after HSV-2 acquisition. We will compare these biopsies to matched control women who are sexually active but remain HSV-2 seronegative.
In year 1 we will conduct an exploratory microarray transcriptome study in an ex vivo vulvovaginal explant tissue model of HSV-2 infection. Our Specific Aim 2 will test whether the frequency of HSV-2 reactivation at set point correlates with the degree of inflammatory changes. We will establish a cohort of HSV-2/HIV negative adolescent women in Thika, Kenya. The women who acquire HSV-2 infection will be enrolled into a 60-day intensive study of HSV-2 shedding, during which they self-collect daily genital swabs for HSV-2 detection. The results on this study will define the role of HSV-2 in mucosal priming of young women for HIV acquisition upon exposure, provide insights into the mechanism, and lay foundation for future interventions for HSV-2, such as chemoprophylaxis, microbicides or vaccines.

Funding Source: NIH/NIAID
End Date: 6-30-18


Quantifying the Impact of Genital Mucosal Inflammation on HIV-1 Acquisition Risk

Florian Hladik, MD, PhD, Co-Investigator (PI: Jairam Lingappa)

Sexual acquisition of HIV-1 is likely accentuated by inflammatory mediators released from genital tissues. Such mediators could be targets for novel HIV-1 prevention interventions. In this study, existing samples and data from African HIV-1 serodiscordant heterosexual couples (one partner HIV-1 infected and the other not) are utilized to quantify the most relevant mucosal mediators
and test their power to predict HIV-1 infection.

Funding Source: NIH/NIAID
End Date: 6-30-18

Extracellular Vesicles in Semen and Genital HIV Infection and Immunity during Heroin Addiction and Methadone or Buprenorphine Substitution Therapy

Florian Hladik, MD, PhD, Principal Investigator

In this project, we study how opioids and extracellular vesicles in semen, alone or in conjunction, impact sexual HIV transmission and immunity to infection. These studies may enable the design of better HIV preventatives (vaccines and microbicides) and inform opioid substitution drug choice in different clinical settings. We will also learn more about the tolerogenic mechanisms allowing conception, as well as opioid immunobiology, with implications for the clinical management of infections in persons who use drugs.

Funding Source: NIH/NIDA
End Date: 6-30-20

Novel Studies of the Effect of Progestin-Containing Contraception on HIV Risk

Florian Hladik, MD, PhD, Co-Investigator (PIs: Jared Baeten & Jairam Lingappa)

Women using certain forms of contraception may have enhanced HIV-1 risk. Using stored samples from African HIV-1 serodiscordant heterosexual couples, a series of innovative clinical and biological studies will be conducted to understand the effect of progestin-based contraception on HIV-1 transmission and disease.

Funding Source: Centers for Disease Control (CDC)
End Date: 8-31-19

Targeted Long-Acting Combination Antiretroviral Therapy (TLC-ART) Program

Florian Hladik, MD, PhD, Co-Investigator/Project 3 Leader (PI: Rodney Ho)

This scientific project focuses on the mucosal side effects of ART and selection of drug resistance.

Funding Source: NIH
End Date: 8-31-20

Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR)

Constance Mao, MD, Co-Investigator (Dr. Zi-Ding Feng, Dr. Barlow, PIs)

Screening through Personalized Regimens (PROSPR) program critically relies on a highly talented and committed PROSPR Statistical Coordinating Center (PSCC) to coordinate the research of PROSPR Research Centers (PRCs) to achieve PROSPR's mission of evaluating and improving the cancer screening process (recruitment, screening, diagnosis, and referral for treatment). The overall objectives of the PSCC are to be accomplished by
1) Providing logistic support for PROSPR meetings and enhance communications and collaborations via a secure PROSPR web portal and a dedicated operations team
2) Providing scientific, clinical, and statistical leadership to enhance PROSPR's scientific vigor and productivity via three organ specific PSCC working groups with the extensive expertise in statistics, clinics, and epidemiology
3) Providing study design, data collection, and data management expertise to enable appropriate pooling of data from studies across PRCs and to lead trans-network cross organ site studies via a statistical team with extensive experience in developing new statistical methodology and in designing and analyzing data for screening studies
4) Providing statistical consultations for PRCs and lead data analyses for pooled PROSPR studies and trans-network studies
5) Serving as a resource to the scientific community for dissemination and outreach of PROSPR data and findings via a PROSPR public portal.
RELEVANCE: Improving screening process for breast, colon, and cervical cancers will reduce mortality, morbidity, and health care cost associated with these cancers in the US.

Funding Source: National Institutes of Health (NIH)
End Date: 1-31-18