RESEARCH ACTIVITIES

All studies conducted through MUWRP have US and Ugandan Institutional and human use approval prior to initiation.  Most MUWRP research studies are reviewed by the HIV/AIDS Research Committee (ARC) of the Uganda National Council for Science and Technology (UNCST) which has a US Federal Wide assurance number.  In addition, if the research involves the Uganda Virus Research Institute (UVRI), e.g. Rakai project collaborations, it undergoes primary review at the UVRI Institutional Review Board (IRB).  In either case, it is then submitted to the UNCST which provides national ethical and scientific review of all research conducted in Uganda. The primary US IRB for MUWRP is the Human Use Review Committee (HURC) of the Walter Reed Army Institute of Research (WRAIR). The US Army Surgeon General Human Subjects Research Review Board (HSRRB) subsequently reviews all HURC approved protocols prior to initiation.  All activities are performed in compliance with the Uganda research guidelines, the US Army, DoD, HHS and other applicable US Federal regulations and ICH.

STUDIES PREVIOUSLY CONDUCTED IN COLLABORATION WITH THE RAKAI HEALTH SCIENCES PROGRAM

Community HIV Epidemiological research (CHER):
Conducted from 1999 – 2002 in collaboration with the Rakai Health Sciences program, this study performed an evaluation of a community based open cohort for the purpose of HIV vaccine trials.  The study performed an annual survey for HIV infection through rural communities in Rakai district.  Approximately 12,000 adults were enrolled in each cycle with approximately 75% follow-up rate.  This study provided HIV counseling and testing, a mobile health care program and provision and assessment of vaccine research information.  A publication in JAIDS (Kiwanuka et al) summarizes the significant improvement in vaccine knowledge through CHER and an overall willingness to participate in HIV vaccine trials of 77%

Molecular Epidemiology Research (MER) Project:
MER is a sub study of CHER. This study recruited HIV sero converters from the annual survey and other HIV activities in Rakai to evaluate early viral and immune markers which may be used as secondary endpoints in future vaccine trials.  In addition, the study provides on-going characterization of the molecular epidemiology of HIV in Rakai and provides reagents for immune assessment and vaccine development.  Through this study, we have established that the current epidemic in Rakai is comprised of pure subtype D in 55%, pure subtype A in 15% and recombinant A/D in the remaining 30%

COMPLETED STUDIES:

RV 156 – A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Multi Clade HIV-DNA Plasmid Vaccine in Uninfected Adult Volunteers.
A Phase I randomized, Placebo controlled, double-blind clinical trial of an HIV-DNA plasmid vaccine to examine tolerability and immune response in the Ugandan population.  The trial enrolled 31 HIV negative people between the ages of 18-40 who were at low risk for HIV and were followed up for a period of one year. Results of Immunogenicity testing are pending but the vaccine was found safe.

RV 173 – Cohort Development for a possible Phase III HIV vaccine Trial among the Adult Population of Kayunga District
A 3 year prospective closed cohort study with prospective, serial six monthly follow-up visits that will determine HIV incidence, Prevalence, risk factors, migration/retention and HIV knowledge among cohort participants. It enrolled a total of 2025 male and female participants aged 15-49 years of age in Kayunga District.  This study is being amended to include the fishing communities of Garilaaya.

ON-GOING STUDIES:

RV 164 – Determination of Laboratory Reference Data using Anonymous Healthy Ugandan Blood Bank Donors
MUWRP concluded a study in collaboration with the Ugandan Blood Bank entitled: "RV-164: Determination of Laboratory Reference Data Using Anonymous Healthy Ugandan Blood Bank Donors". Approximately 6000 anonymous samples were collected from healthy blood donors in Kampala, Fort Portal, Gulu, Mbararra and Mbale disticts to address several important objectives.
The first objective of the study was to establish normal reference ranges for clinical chemistry, hematology, and lymphocyte subsets for blood bank donors in the Kampala area. This objective was met and relevant reference ranges were established and are currently being used to evaluate the safety of ongoing HIV vaccine trials at MUWRP. A manuscript outlining these details is currently being prepared.
Other objectives of the study were;

• To validate the use of rapid HIV testing using both sero positive and sero negative samples.
• To further characterize Uganda as a whole for future vaccine development by evaluating the prevalence of different subtypes of HIV in Kampala and at the different regional centers throughout Uganda.
• To determine point prevalence of antibodies to adenovirus, adenovirus associated virus and other viral vectors used in experimental HIV vaccines.

The results from the second objective of the study have been recently published in the Journal of Clinical Microbiology [Eller, L. A., M. A. Eller, et al. (2007). "Large-scale Human Immunodeficiency Virus rapid test evaluation in a low-prevalence Ugandan blood bank population." J Clin Microbiol 45(10): 3281-5.]

RV 156A – An Amendment to Protocol RV 156
A phase I clinical trial to evaluate the safety and immunogenicity of a multiclade HIV-1 recombinant Adenovirus-5 vector vaccine, VRC-HIV ADV014-00-VP administered alone or administered as a boost to a multiclade HIV-1 DNA Plasmid vaccine, VRC-HIVDNA009-00-VP, in uninfected adult volunteers in Uganda. This is a single site Phase I open label study with accrual restricted to volunteers in RV 156. All volunteers (placebo and DNA vaccine recipients alike) received open label VRC HIV rAD5 vaccine.  They are all being evaluated for immunogenicity and clinical safety assessment at regular intervals for about 1 year after vaccination.

RV 172 – A Phase I/II Multi Site Clinical Trial to Evaluate the Safety and Immunogenicity of a Multiclade HIV-1DNA Plasmid vaccine, VRC-HIVDNA016-00-VP, Boosted by a Multiclade HIV-1 Recombinant Adenovirus-5 Vector Vaccine, VRC-HIVADV014-00-VP in HIV Uninfected Adult Volunteers in East Africa 
This is a multi-center, randomized, placebo controlled double blind study being conducted at 3 sites in East Africa.  The study enrolled 324 healthy HIV-1 uninfected adult volunteers aged 18-50 years.  All vaccinations were completed at all sites in April 2007 and follow-up visits were completed September 2007. No safety concerns for acute reactogenicity or adverse events have been recognized.  The study has shown excellent immunogenicity for HIV antigens.

UPCOMING STUDIES:

RV 217 - HIV-1 Prevalence, Incidence, Cohort Retention, Host Genetics
and Viral Diversity in High Risk Cohorts in East Africa and Thailand
This is a multi-site high risk cohort that will enroll 2000 participants from three East African USMHRP sites and Thailand. MUWRP will contribute a 500 of these participants. The study is expected to start early 2008.

RV 247 - Ebola/Marburg Vaccine trial:
This is a phase IB study to evaluate the safety and Immunogenicity of an Ebola DNA Plasmid Vaccine, VRC-EBOLDNA023-00-VP and a Marburg DNA Plasmid Vaccine, VRC-MARDNA025-00-VP, in Healthy Adults in Kampala Uganda.
The study will enroll 108 healthy volunteers aged 18-50 from Kampala. It is expected to start mid 2008.