Human immunodeficiency virus (HIV) has been known to be associated with primary central nervous system (CNS) manifestations in form of cognitive, behavioral, and affective symptoms. In the absence of opportunistic infections, the initial diagnosis of HAND (HIV-associated neurocognitive disorder) is difficult to suspect based on above in middle-aged adults, which commonly is misinterpreted as part of psychiatric disorders. Once HIV is diagnosed on serological testing, the personality changes are often colored by cognitive deficits induced by the illness itself, or because of antiretroviral treatment (ART) induced adverse effects, which can interfere with treatment compliance and worsening of HIV status. Acute onset alteration in mental status is known to happen with ART and HIV. With HIV, it can occur either because of primary CNS infection or opportunistic infections, whereas particular medications of ART were known to cause neuro-psychiatric manifestations ranging from anxiety, sleep disturbances, and short-lived increased dreams to psychosis. However, switching into aberrant states of consciousness with intense perceptual alterations for prolonged periods has rarely been reported. This case report highlights the importance of unique psychopathology and clinical helplessness in case of HAND, where cost-benefit of treatment change and psychoeducation of the family was a challenge.