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PURPOSE OF REVIEW: To review recent studies that address the pathogenesis, diagnosis and treatment of HIV positive patients with cryptococcal and tuberculous meningitis and progressive multifocal leukoencephalopathy in resource-different settings. RECENT FINDINGS: Central nervous system opportunistic infections remain globally prevalent in HIV+ populations. Several recent papers have highlighted the urgent need for rapid point of care tests in low-income settings for cryptococcal and tuberculous meningitis, better access to antifungal therapy for cryptococcal meningitis and better treatment strategies for tuberculous meningitis. In one recent study of 299 HIV+ patients with cryptococcal meningitis, amphotericin plus flucytosine was associated with less mortality and disability compared to amphotericin alone. In a study of patients with tuberculous meningitis in Indonesia, short-term, high dose rifampicin and moxifloxacin, designed to achieve higher levels of anti-TB drugs in the brain, saw significantly reduced patient mortality at 6 months. The timing of ART initiation in patients with central nervous system opportunistic infections remains challenging and a recent study reported that deferred vs early antiretroviral therapy was associated with better survival outcomes in patients diagnosed with cryptococcal meningitis. Recent studies have reported on predictors of immune reconstitution inflammatory syndrome for patients with central nervous system opportunistic infections, but require validation in resource-different settings. SUMMARY: Recent studies related to the diagnosis and treatment of central nervous system opportunistic infections in HIV+ populations show promising findings. Increased funding and research commitment are required to maintain this positive momentum and to achieve improved global outcomes for people who develop central nervous system opportunistic infections.