Human cohort studies
RV 398
SAFETY AND VIROLOGIC EFFECT OF A HUMAN MONOCLONAL ANTIBODY, VRC-HIVMAB060-00-AB (VRC01), WITH BROAD HIV-1 NEUTRALIZING ACTIVITY, ADMINISTERED INTRAVENOUSLY TO ADULTS DURING EARLY ACUTE HIV INFECTION
This is a multi-center study conducted in three East African countries (Tanzania, Kenya, Uganda) and Thailand. The participants obtained from RV 217 cohort.The study product (VRC01) is a broadly neutralizing human mAb targeted against the HIV-1 CD4 binding site. It was developed by the VRC/NIAID/NIH. VRC01 is of the Immunoglobulin G1 (IgG1) subtype and is highly somatically mutated from its germ-line precursor. The heavy chain CDR3 region is 14 amino acids long, which is an average length relative to natural antibodies, and the glycosylation pattern is derived from its production in a Chinese Hamster Ovary (CHO) mammalian cell line.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS (DAIDS),
National Institutes of Health (NIH) Bethesda, Maryland
NVBD
Epidemiology of Neglected Viral and Bacterial Diseases in the Mbeya Region
Purpose
NVBD (Epidemiology of Neglected Viral and Bacterial Diseases in the Mbeya Region) is a substudy of the EMINI project. Within NVBD, 1300 blood samples from selected EMINI participants are examined to establish epidemiological data on six arbovirus infections (Chikungunya, Dengue, Yellow Fever, Rift Valley Fever, O' nyong nyong), as well on bacterial zoonotic diseases which affect human health as well as lifestock breeding success. Among the latter are Plague, Rickettsioses and Brucellosis.
RV 217
Early Capture of HIV Cohort (ECHO)
Description of the study
Title: HIV-1 Prevalence, Incidence, Cohort Retention, and Host Genetics and Viral Diversity in Cohorts in East Africa and Thailand”
This is a multi-center, non-randomized clinical observational study conducted in three East African countries (Tanzania, Kenya, Uganda) and Thailand. The research collaboration outlined in this study measures the epidemiology of HIV in a volunteer cohort drawn from high-risk populations in these countries. The study focus more on acute infection acquisition rather than high risk cohort development alone.
WHIS Project
Intestinal helminth infections and schistosomiasis and their relation to HIV-1 incidence, disease progression and immunology in Mbeya Region, Tanzania
Purpose
WHIS aims to examine the influence of helminth infections on the epidemiology and immunology of HIV infection. Specific objectives are
i.to assess the possible influence of different Helminth infections (Ascaris lumbricoides, Trichuris trichiura, Hookworm, Schistosoma haematobium and S. mansoni) on HIV prevalence, incidence and disease progression.
ii.to investigate whether and how different kinds of helminth infections change the human immune response to HIV, TB and other infectious diseases and to examine the possibility that helminth-infection increases the susceptibility of CD25 and CD4 T cells to infection with the Human Immunodeficiency Virus.
Furthermore WHIS includes a capacity building component that aims to provide PhD and MSc training to two young scientists from Tanzania.
Active Detection of Tuberculosis in Children
Background
The diagnosis of childhood tuberculosis remains a major challenge of TB control, especially in developing countries. Causes of misdiagnosis include non-specific clinical signs or symptoms and low sensitivities of e.g. AFB microscopy, especially in HIV co-infected children.
This pilot study started in May 2008 with the objective to provide an improved approach to TB diagnosis in HIV infected and uninfected children through evaluation of emerging innovative diagnostic methods. Furthermore, in an extension to the original study, a closer look is taken at the clinical and immunological treatment outcome of TB infected children and at the diagnosis and prevalence of immune reconstitution inflammatory syndromes (IRIS) in HIV co-infected children.
Date of first enrolment was the 29th May 2008. Eligible participants are all children between the age of 6 weeks and 14 years of age with clinical suspicion of having either intra- or extra-pulmonary TB.
EMINI Project
EMINI - Establishment of the infrastructure for the Evaluation and Monitoring of the Impact of New Interventions
Purpose
The overall objective of the EMINI project is to contribute to the overall improvement of health by trying to help control two of the three major communicable diseases in Africa. This overall objective should be achieved through two specific objectives. These are
i. The reinforcement of the existing health care structures so they become conducive to new interventions
ii. The establishment of an up-to-date capacity to evaluate and monitor the impact of improved health care infrastructure and new interventions.
These new interventions include drugs and vaccines for HIV, TB and malaria and active TB case finding; just to mention some of them. The target group for this action is the general population of the Mbeya Region.
As part of the second objective the study aims to describe the epidemiology of infectious diseases, including HIV, TB, malaria, schistosomiasis and helminth infections and causes of morbidity in the studied population. The study shall also establish the data that are required for community randomized controlled trials.
Cohort Development (CODE) Project
Description
This study was realised in collaboration with Walter Reed Army Institute of Research. Three different kinds of cohort recruiting were compared. Over a four year period, HIV incidence and prevalence rates were determined, basal data for viral load, cd4 and cd8 kinetics, risk behaviour and follow-up rates was generated.
Through an information campaign, knowledge about vaccine studies, and willingness to participate in such studies has been improved. In September 2005, the 3,000 participants have been observed for three years. HIV prevalence was determined to be 18,4% in urban and 12,2% in rural population, incidence of new infection was 1,6%, and interestingly was higher in rural than in urban areas. Follow-up rate after three years was 85%.
Project Coordinator L. Maboko
HIV Super Infection Study (HISIS)
Decription
basing on samples obtained from 600 prostitutes in during the HISIS study, correlates of protective immunity are evaluated. In a case-control-study, cellular immunity is examined using ELISPOT and intracellular cytokine staining (ICC) in three subgroups:
Women massively exposed to HIV during three years as prostitutes, who are HIV-negative;
Women infected with HIV once, whose immune response is preventing superinfection with another HIV strain;
Women whose immune response is insufficient to prevent infection, resulting in several infections with HIV.
Thus, correlates of protective immunity shall be identified. First results how certain HLA alleles (B5801, B8101, B0702) to induce a borader immunity in gag, which contributes to a long-term reduction in viral load by two log steps.
LMU Department of Infectious Diseases and Tropical Medicine is participating in this activity through its immunologists L. Podola, PhD and C. Geldmacher, PhD, who are planning and analysing this study together with colleagues in the NIMR-MMRC immunology laboratory.
Project Coordinator: L. Maboko
