PI: Mohamed Abdel-Mohsen, PhD
The Wistar Institute, Philadelphia, PA
Novel Glycomic Biomarkers Predicting Time to HIV Rebound after Treatment Interruption
The field of glycoproteomics, which identifies the signature of sugars attached to proteins in the body, has found that a protein's function can change depending on the types of sugars it carries. Dr. Mohamed Abdel-Mohsen has discovered that the presence of certain sugars on the patient's antibodies correlates with the size of the viral reservoir and with other clinical features of disease. In the present study, he aims to turn his glycoproteomic work to predicting post-treatment control-HIV remission experienced by the rare individuals who continue to control their virus even after ART cessation. Dr. Abdel-Mohsen's work could lead to the identification of molecular predictors that would identify PTCs before they stop ART.
PI: John Frater, MD, PhD, FRCP
The Chancellor, Masters and Scholars of the University of Oxford, Oxford, Oxfordshire, United Kingdom
Immunological, Genetic and Virological Analysis of HIV Remission in the HEATHER Cohort-the PITCH Study Arm
Post-treatment controllers (PTCs), people who are able to control their virus even after stopping ART, may hold the key to understanding how the immune system naturally controls the virus and how prior ART exposure may be enabling subsequent control of HIV. Dr. John Frater has been a leading researcher on PTCs, and now proposes a prospective PTC study that will allow for the analysis of samples before a patient begins ART, which is important in determining the role of ART in the patient's subsequent control. Dr. Frater's findings could be key to curative immune interventions or interventions that enable remission.
PI: Edward Kankaka, MBChB, MPH
Rakai Health Sciences Program, Kampala, Uganda
Temporal phylogenetic characterization of the latent HIV reservoir in a cohort of virally suppressed Ugandans
The majority of what is known about HIV comes from research done in high-income countries where the circulating HIV clade is subtype B and makes up only 12% of the global HIV infection. The Rakai Cohort in Uganda is an 18,000-person study that aims to increase what is known about infections with other, non-B HIV. Recently, a study undertaken by Dr. Edward Kankaka of the Rakai Cohort showed that non-B HIV infected Ugandans had a lower reservoir size compared to clade B infected participants in Baltimore. Dr. Kankaka plans to expand these studies by determining whether formation and maintenance of the reservoir differ in these populations. His findings would add to the understanding of how curative interventions would fare in non-clade B infected people.
PI: Jonathan Li, MD, MMSc
The Brigham and Women's Hospital, Boston, MA
Determinants of HIV Rebound and Remission
HIV remission, controlling the virus after stopping ART, is achieved by a small fraction of patients and is a field of active study made difficult by the rarity of these individuals. Dr. Jonathan Li has assembled one of the largest cohorts of these post-treatment controllers (PTCs) and aims to identify predictors of control. Using next generation genomic sequencing, Dr. Li will investigate whether characteristics of the virus, or immunologic responses, are predictive of HIV remission. Understanding the combination of factors underlying existing cases of PTC could help scientists design interventions for people who would otherwise not control their virus without ART.
PI: Godwin Nchinda, PhD
Chantal Biya International Reference Center for Research on the Prevention and Management of HIV/AIDS, Yaounde, Center Region Cameroon
Characterization of HIV infected women that maintain without HAART sustained undetectable viral load following PMTCT
In 2011, the African Dendritic Cell Targeted Vaccine Cohort, AFRODEC, was established in Cameroon to identify prospective vaccine candidates and today it has grown to include nearly 700 people. Dr. Godwin Nchinda has followed this cohort since the beginning and has identified groups of particular interest within the cohort such as elite controllers. For this proposed project, Dr. Nchinda has identified a second group, namely women who have received ART during their pregnancy and continue to control the virus despite halting ART postpartum. Dr. Nchinda will characterize this group to understand the underpinnings of their viral control. These valuable studies could identify novel ways of bringing about HIV remission-viral control in the absence of ART.
PI: Reena Rajasuriar, PhD
University of Malaya, Kuala Lumpur, Malaysia
HIV persistence and antigen-specific immunity: The HIV Hygiene Hypothesis
The number and type of cells making up our immune system constantly fluctuates in response to pathogens in our environment. A small fraction of the cells that expand and contract in number are HIV reservoir cells that, even though they harbor HIV, may be specifically trained to fight a different pathogen. Dr. Reena Rajasuriar is testing whether frequent exposure to pathogens commonly encountered by people living in low-income countries expands the HIV reservoir differently compared to high-income countries, where exposure to these pathogens is lower. Dr. Rajasuriar is comparing clonal expansion in patients living in San Francisco to that in Malaysia and in the process bringing the field closer to understanding whether HIV reservoirs in high- and low-income countries may demand different curative interventions.
PI: Alex Sigal, PhD
Africa Health Research Institute, Durban, KwaZulu-Natal, South Africa
HIV Persistence in Lymph Nodes in the Face of ART in TB Infected Individuals.
Tuberculosis (TB) is a common coinfection in people living with HIV in low- and middle-income countries. Like HIV, TB infection fluctuates between active and latent states, but how these states affect the HIV reservoir is unknown. Dr. Alex Sigal, researcher at the Africa Health Research Institute, has accumulated an impressive cohort of lymph node biopsies that could answer this question. Dr. Sigal will determine whether the composition of the HIV reservoir changes in response to active, latent, or cured TB. Furthermore, Dr. Sigal will explore whether the immune response to TB itself alters HIV reactivation-a key component to the "shock and kill" curative approach. For the 90% of people living with HIV in low- and middle-income countries, Dr. Sigal's work will shed necessary light on the challenges TB could impose on an HIV cure.
PI: Rui Wang, PhD
Harvard Pilgrim Health Care Institute, Wellesley, MA
Mechanistic and Empirical Modeling of Viral Rebound to Identify Predictors of Post-Treatment Control
Antiretroviral treatment interruptions have become a necessary risk in determining whether a curative intervention is effective. The challenges to the patient of frequent monitoring during the interruption and the risk of infection to the patient's partners are substantial considerations when determining whether a treatment interruption is necessary. Dr. Rui Wang proposes to use her expertise in computational biology to predict before the treatment interruption is initiated the time at which a patient's virus will rebound after treatment interruption. Dr. Wang will combine clinical data from multiple studies before and after treatment interruption and apply innovative mathematical models that combine both what is known about the biology of the disease and models that can identify new knowledge.