HIV invades the central nervous system (CNS) during early infection and contributes to neurocognitive impairment during chronic infection. This thesis aims to investigate the neurological impact of acute HIV infection (AHI) and its outcomes after immediate initiation of antiretroviral therapy (ART). Section 1 of this thesis is an introduction to the persistence of HIV-associated neurocognitive disorder in the ART era, highlighting the need to study AHI to understand HIV neuropathogenesis. The main body of the thesis describes the outcomes of the RV254 Thai AHI cohort, in which all participants were enrolled during AHI and initiated ART within days after the diagnosis. Section 2 focuses on the findings during AHI, examining the determinant of HIV-1 RNA level in cerebrospinal fluid (CSF), the impact of concomitant syphilis, and the safety of performing lumbar punctures during AHI. Section 3 discusses the longitudinal outcomes of RV254 participants after ART, presenting their 6-year neurocognitive trajectory, the neuropsychological impact of switching from a Efavirenz-based ART to a Dolutegravir-based ART regimen, and the rare detection of HIV-1 RNA in CSF during plasma HIV-1 suppression (CSF HIV-1 escape). Section 4 explores the implications of CNS in HIV cure research. The findings suggest that HIV-1 invades the CNS during acute infection and causes abnormal neurological signs, neurocognitive dysfunction and depressive mood. Yet, prompt initiation of ART during AHI could reverse these abnormalities - RV254 participants on stable ART are generally free from neuropsychiatric complications frequently seen in other HIV-positive populations, highlighting the benefit of early ART in HIV infection
