It is becoming increasingly evident that antiretroviral treatment is not a long-term solution for HIV- infected subjects. The increased incidence of cardiovascular diseases and other serious complications associated with ART have prompted the efforts to examine viral resurgence upon treatment interruption. Large numbers of studies have reported that the majority of people who undergo treatment interruption would experience viral rebound. But recent studies reported that a small number of subjects that initiated ART in acute infection achieved natural control of HIV replication after ART cessation without having the genetic characteristics of elite controllers, providing the proof of concept for a natural contol of viral replication after analytical treatment interruption (ATI). Identifying key immunological factors responsible for this natural control of viral replication after ART withdrawal is crucial fr the development of successful immunotherapeutic interventions to achieve a status that would allow natural control of viral replication in the absence of ART in most individuals. We hypothesize that very early ART preserves functional CD8, CD4 and antibody memory and effector responses and this will enable efficient viral control upon cessation of ART. The major objective of this proposal is to identify immune parameters preserved by very early ART initiation and associated with viral control after ATI. In this grant, we will follow a group of HI-infected subjects from the RV24 cohort treated in the first two weeks of infection and that will remain under ART for at least three years. Importantly, we will monitor these same HIV-infected subjects for their ability to control viremia upon ATI. The RV254 cohort provides the best setting to study optimal immune responses associated with viral control in subjects that are not genetically predisposed to control. By examining this unique cohort before and after treatment interruption, we will be able determine whether preserved memory T cell responses and better effector T and B cells are associated with control of viral replication after ATI.

Public Health Relevance

In this proposal we will identify immune parameters that are preserved by very early initiation of ART prior to immune damages caused of HIV infection. We will determine whether these preserved immune parameters can be associated with viral control after treatment interruption in the unique RV254 acute HIV infection cohort, in which HIV- infected subjects are treated very early within the first 20 days of infection and will undergo treatment interruption after at least 3 years of ART. Identifying key immunological parameters responsible for the natural control of viral replication after ART withdrawal is crucial for the development of successful immunotherapeutic interventions.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS Immunology and Pathogenesis Study Section (AIP)
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Sanders, Brigitte E
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Vgti Florida
Port Saint Lucie
United States
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Colby, Donn J; Trautmann, Lydie; Pinyakorn, Suteeraporn et al. (2018) Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection. Nat Med 24:923-926
Kessing, Cari F; Spudich, Serena; Valcour, Victor et al. (2017) High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. J Acquir Immune Defic Syndr 75:108-117
Takata, Hiroshi; Buranapraditkun, Supranee; Kessing, Cari et al. (2017) Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection. Sci Transl Med 9:
Trautmann, Lydie (2016) Kill: boosting HIV-specific immune responses. Curr Opin HIV AIDS 11:409-16
Muir, Roshell; Metcalf, Talibah; Tardif, Virginie et al. (2016) Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection. PLoS Pathog 12:e1005777