Identification of Broadly HIV-1 Neutralizing Antibodies (bNAb) in HIV-infected Patients in Mbeya, Tanzania. (bNAb)

In natural HIV disease, a small fraction (1-2%) of infected individuals develops exceptionally high titres of HIV-1 neutralizing serum activity. Antibodies isolated from these individuals have been shown to be highly active against a broad range of different HIV strains and are therefore called broadly neutralizing antibodies (bNAbs). These antibodies are in fact able to prevent (S)HIV infection in animal models and therefore of great interest for the development of an HIV vaccine. Information of neutralizing antibodies in patients from Africa is still scarce and would be of great value in the development of adapted HIV vaccine strategies in these regions. This study aims to investigate African HIV-infected individuals, who have developed neutralizing antibodies using highly specialized laboratory methodologies.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV/AIDS

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• Tanzania
  • Mbeya, Tanzania
    • NIMR-Mbeya Medical Research Center (MMRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult HIV-infected, preferentially ART-naïve patients within the Mbeya region. The prevalence of elite neutralizers is expected to be 1-2% from the overall population. The study therefore targets to recruit 500 subjects in order to identify at least 5 elite neutralizers, which will be subjected to further in depth antibody characterization.

Description

Inclusion Criteria:

1. Voluntary and informed consent
2. ≥18 years of age
3. Documented HIV infection.
4. Willing to consent to active tracing including home tracing

Exclusion Criteria:

1. Deficiency, rendering it difficult, if not impossible, to take part in the study or understand the information provided. This includes alcoholism, drug dependency as well as psychiatric illnesses, suicidal tendencies or any other inability.
2. Prisoners
3. If within the discretion of the investigator study participation would possibly add not acceptable risk or burden to patient (e.g. significant health deficiencies, social harm)
4. Unlikely to comply with protocol as judged by the principal investigator or his designate

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Broadly HIV-1 neutralizing antibodies (bNAb)	identify HIV-infected patients which exhibit exceptional HIV-1 neutralizing activity (so called elite neutralizer) and to perform in those patients in depth characterization including: Detailed analysis of anti-HIV antibody response using single B cell analyis; Isolation of broadly neutralizing anti-HIV antibodies; Testing of in vitro neutralizing activity and binding properties of newly identified bNAbs; Analysis of the antiviral activity and in vivo characteristics of broadly neutralizing antibodies using a HIV-1-infected humanized mouse model	December 31, 2018

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize HIV subtypes in elite neutralizer and optionally in non-neutralizer	December 31, 2018
To characterize demographic and HIV status related factors associated with elite neutralizers and non-neutralizers	December 31, 2018
To optionally investigate the proportion of patients with transmitted drug mutations (genotypic drug resistance)	December 31, 2018

Collaborators and Investigators

• Sponsor: Michael Hoelscher
• Collaborators: National Institute for Medical Research - Mbeya Medical Research Centre (NIMR-MMRC); University Clinic of Cologne, Department of Internal Medicine, Center for Molecular Medicine Cologne (CMMC); Max von Pettenkofer-Institute of the University of Munich (LMU), Department of Virology
• Investigators: Study Chair: Arne Kroidl, Dr., Medical Center of the University of Munich, Division of Infectious Diseases and Tropical Medicine, Germany; Principal Investigator: Wiston William, Dr., NIMR-Mbeya Medical Research Center (MMRC), Tazania

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2017
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: LMU-IMPH-bNAb

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No