Active Studies
RV254 (SEARCH 010) is an observational study in Bangkok, Thailand. The study team screens 30,000 people living with HIV each year with a target of capturing 40-50 AHI participants per year. Participants are enrolled at the Anonymous Clinic of the Thai Red Cross AIDS Research Centre, and undergo full neurological and neuropsychological evaluation at baseline and annually. Blood, plasma, and CSF specimens are captured and stored for virological and immunological assays, and participants also undergo MRI. Participants may participate in optional procedures including collection of genital secretions, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy.
RV304 (SEARCH 013) is operated in Bangkok, Thailand, where study staff perform gut biopsies, lymph node biopsies, lumbar punctures, and/or blood draws on 100 HIV-uninfected and 100 people living with HIV. This study will provide important control data of HIV-uninfected and HIV chronic participants for comparison with the AHI cohort of RV254/SEARCH010. Study participants are recruited from the Thai Red Cross Anonymous Clinic (TRCAC), Chulalongkorn University Hospital in Bangkok, and the ECHO center in Pattaya.
RV329 (AFRICOS) is an observational study operating at five sites in Africa, with the goal of enrolling 3,600 HIV-infected and 600 people living with HIV. Study sites are in Kenya, Nigeria, Tanzania, and Uganda. The primary objective of this study is to assess the impact of clinical practices, biological factors, and socio-behavioral issues on HIV infection and disease progression over time in an African context.
RV550 is an HIV remission trial in Bangkok, Thailand enrolling participants from the RV254 cohort. This controlled trial is investigating the safety, tolerability, and immunomodulation effect of combining N-803 with ART during AHI.
RV630/DELIVER-01 is an HIV remission trial operated in Bangkok, Thailand that enrolls participants from the RV254 cohort. The goal of the study is to determine if a combination of broadly neutralizing antibodies (bNAbs) and therapeutic vaccination will be safe and will elicit HIV-specific immune responses that may potentially kill infected cells and lead to ART-free viral control. A total of 40 people with HIV will be enrolled, with 20 receiving the combination bNAbs and vaccine and 20 receiving bNAbs only.
RV633 is operated in Bangkok, Thailand and enrolls participants from the RV254 and RV304 cohorts to determine if there is peripheral endothelial dysfunction during acute HIV infection and after antiretroviral therapy compared to HIV negative participants. The objective of this study is to understand the onset and pathophysiology of system and central nervous system vasculopathy in people with very early HIV infection and to identify biomarkers of endothelial dysfunction that can be targeted for early interventions to improve cerebrovascular health in people with HIV globally.
RV412 (SEARCH 025) is a surveillance study for people living with HIV who complete a treatment interruption study. This study includes an open cohort without restriction on sample size, though enrollment is not expected to exceed 500 participants. The study site in in Bangkok, Thailand and the study recruits from the interruption studies listed above. Participants not on ART at study start are monitored closely and put back on ART once rebound is detected.
Longitudinal determination of nervous system consequences of SARS-CoV-2 in virologically suppressed people with HIV-1 treated in early infection is an observational study examining pre- and post-COVID-19 data in RV254 participants to provide key information regarding the combined effects of SARS-CoV-2 and HIV on the brain. We hypothesize that a ‘second hit’ infection with SARS-CoV-2 – known to be associated with neuroimmune alterations, vascular damage, and neuronal injury – may incite transient or lasting detrimental changes in central nervous system parameters and cognitive and mental health outcomes in well treated people with HIV.
Sexual Network Substudy was conceived to investigate the role of sexual networks in influencing HIV risk among MSM in Thailand, since HIV risk is based not solely on personal risk behaviors but also risk behaviors of those in one's sexual network. An expected sample size of 150 HIV-infected MSM enrolled in RV 254 (SEARCH 010) in Bangkok, Thailand will undergo both egocentric and sociometric network analyses. This study aims to describe structural and compositional characteristics of sexual networks of Thai MSM with acute HIV infection as well as changes in sexual networks over time.
Modeling Neurologic Involvement in Nonhuman Primates is being conducted at the Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok, Thailand in their US-Army run, AAALAC-accredited vivarium and associated research laboratories. Hybrid simian-human immunodeficiency virus is being used as a clinically relevant, non-accelerated model of HIV disease prior to end-stage encephalitis to understand the pathogenesis of early neurologic involvement in the CNS, and to study the effect of ART and future therapeutic interventions on the brain, CSF and on cognitive and motor function.
Completed Studies
RV398 was a protocol designed to study the co-administration of a vaccine and ART. Each arm of this study enrolled up to 8 participants for a total sample size of 24. Study sites were located in:
- Bangkok, Thailand
- Kericho, Kenya
- Kampala, Uganda
- Mbeya, Tanzania
RV397 (SEARCH 24) was a treatment interruption study to test the efficacy of vaccine administration during analytical treatment interruption (ATI). The study enrolled people with HIV who initiated antiretroviral therapy (ART) within the first few weeks of infection and who successfully suppressed their viral load with ART for at least 1 year. The study site was in Bangkok, Thailand. This study recruited from RV 254 (SEARCH 010). As in all interruption studies, participants were monitored frequently and put back on ART once rebound was detected.
RV405 (SEARCH 023) was a treatment interruption study that administered a vaccine and a mosaic before ATI. People living with HIV were enrolled in Bangkok, Thailand from RV 254/SEARCH 010, and only participants who had ART initiated during AHI were eligible. A total of 36 participants were enrolled in a 2:1 ratio of vaccine/mosaic (n=24) to placebo (n=12). As in all interruption studies, participants were monitored frequently and put back on ART once rebound was detected.
RV408 (SEARCH 018) examined the nervous system impact of administration of an adjunctive anti-inflammatory therapy with ART during acute HIV infection. A total of 21 people living with HIV were enrolled, with 14 receiving ART plus the adjunctive treatment, and 7 receiving ART only. This study occurred in Bangkok, Thailand and participants were recruited from RV 254 (SEARCH 010).
RV411 (SEARCH 022) was a treatment interruption study that tracked ATI on people living with HIV who had ART for at least 2 years. An initial 8 participants were assessed 12 weeks after ATI to determine the safety of the study. Once least one of these participants maintained viral suppression after 12 weeks, an additional 7 participants were recruited for a total sample size of 15. This study took place in Bangkok, Thailand and recruited from RV 254 (SEARCH 010). As in all interruption studies, people living with HIV were monitored frequently and put back on ART once rebound was detected.
RV424 (SEARCH 026, Neuro substudy of RV409/SEARCH 019) was a treatment interruption study designed to investigate the nervous system effects of co-administration of a histone deacetylase (HDAC) inhibitor combined with other medications and ART, followed by ATI. The total sample size was 15 with a 2:1 ratio of people living with HIV receiving ART and the HDAC inhibitor intervention to participants receiving ART only. The study site was in Bangkok, Thailand and recruited people living with HIV who had been on ART for at least 42 weeks from RV 254 (SEARCH 010). As in all interruption studies, participants were monitored frequently and put back on ART once rebound was detected.
RV436 (SEARCH 027, Decision-making Substudy of RV254/SEARCH 010) was conducted in coordination with the RV 254 (SEARCH 010)-affiliated HIV cure trials, which offered unique opportunities to learn from both participants and decliners about decision-making and expectations of potential risks and benefits. After completing a 20-minute pre-decision survey, approximately 54 individuals who decided to enroll in an HIV remission trial and 20 individuals who elected not to enroll completed three 60-minute interviews throughout the course of the clinical trial (two interviews for the decliners). Approximately 400 members of the SEARCH010 cohort have also taken a longer survey, including questions about living with HIV and ART, perceptions of hypothetical scenarios about ART treatment interruption, and experiences with optional research procedures. The knowledge gained will inform participant engagement, the informed consent process, and design of future HIV cure studies.
Impact of Treatment on Brain Integrity in the Earliest Stages of HIV Infection was an observational study that recruited participants from RV254 and RV304 to understand whether ART is sufficient to halt the detrimental impact of HIV on the brain when initiated within weeks of infection, or whether brain abnormalities progress beyond expectations for HIV- controls despite otherwise successful treatment. The study leveraged longitudinal multimodal imaging outcomes (resting state fMRI, diffusion tensor imaging, and structural volumetrics) of participants treated in acute infection compared to demographically-similar individuals with chronic HIV and HIV- controls. Evidence of persistent neural injury despite ART initiated during acute infection would help identify key mechanisms of HIV neuropathogenesis and potential targets for clinical interventions.