Acute HIV infection and HIV cure are the focus of SEARCH Research Foundation. The backbone of these efforts is the SEARCH010/RV254 prospective cohort study, which we describe here in some detail as it best exemplifies our scientific, logistical and regulatory capabilities. Around 40,000 consenting individuals are screened each year overnight after presenting for HIV testing, to identify 50 to 100 with acute HIV infection (AHI; routine antibody and antigen testing still negative, only PCR positive. Diagnosing HIV in the acute stage overnight through our collaboration with the Armed Forces Research Institute of Medical Sciences (AFRIMS), provides investigators with the opportunity to understand the events immediately following infection by studying viral and cellular activity in relevant body compartments Study participants undergo neurological and neuropsychological evaluation combined with brain MRI/MRA. Blood, lymph node, gut tissue and cerebrospinal fluid are also captured in consenting volunteers and tested by virological and immunological assays among 57 collaborators at 45 institutions globally, to make sure that the samples and data provided by the volunteers optimally serve science and the global effort to find an HIV cure.

The SEARCH010/RV254 cohort study is complemented by the SEARCH013/RV304 study in which SEARCH enrolls volunteers who are either HIV negative or living with chronic HIV infection who serve as controls that allow for correct interpretation of the data generated in SEARCH010/RV254. Their biological sampling follows the time-points of the SEARCH010/RV254 study.

The setting of the SEARCH010/RV254 cohort study and the SEARCH013/RV304 control offers a unique research opportunity to investigate the interactions between HIV-1 and the central nervous system (CNS) at the time of AHI. Our Neuro HIV work is guided by the International Neuro HIV Cure Consortium (www.inhcc.net) and executed with academic collaborators at Yale, UCSF, Missouri Institute of Mental Health, Oregon Health Sciences University, Weill Cornell School of Medicine, and University of Hawaii. Collaborators from the INHCC examines the participants’ neurological profiles through required neurological examination, mood disorders screening, neurocognitive assessment and optional lumbar punctures and magnetic resonance imaging (MRI) of the brain.

The SEARCH010/RV254 participants serve as a valuable resource for the increasing interest in the field of HIV cure. HIV Remission or cure studies explored the potential of HIV remission with or without treatment interruption with very early ART (RV411), therapeutic HIV vaccine (RV405), broadly neutralizing antibodies (RV397 and RV398) and drugs targeting the HIV reservoir (RV550) have been completed or currently on going with participants enrolled from the SEARCH010/RV254 study. The field is currently moving towards combining interventions that decrease the so-called latent HIV reservoir, which needs to be limited to attain HIV remission, with interventions that boost the immune system to control whatever HIV reservoir remains. One study, SEARCH036/RV550, which investigates the effect of an IL-15 superagonist on the lymph nodes is currently underway. Another study (SEARCH038/RV582) related to HIV cure/remission combining these cure strategies is currently in preparation. Participants who finish the HIV cure studies are then followed up in SEARCH025/RV412.