INTRODUCTION: The population of aging adults living with Human Immunodeficiency Virus (HIV) is growing worldwide and evidence suggests that frailty occurs prematurely among them. In turn, frailty has been associated with cognitive decline. It is unknown, however, if people with both frailty and HIV-infection have higher risk of cognitive impairment compared with non-frail HIV-infected persons. Therefore, the main objective of this study was to determine the association between the phenotype of frailty and HIV-associated neurocognitive disorders (HAND) among adults aged 50 years or older living with HIV/AIDS. MATERIAL AND METHODS: A cross-sectional study was conducted on 206 adults living with HIV receiving care in a university-affiliated tertiary care hospital in Mexico City. Frailty was defined as per the Fried criteria. The presence of HAND was established according to the Antinori criteria: HIV-associated asymptomatic neurocognitive impairment (ANI), HIV-associated mild neurocognitive disorder (MND), or cognitively non-impaired. Multinomial logistic regression models were used to test the independent association between frailty and HAND adjusting for potential confounders. RESULTS: Mean age of participants was 60.5 +/- 6.3 years and 84.9% were male. Prevalence of HAND and frailty phenotype was 66.0% and 2.9 %, respectively. The unadjusted analysis showed that both prefrail and frail statuses were associated with MND but not with ANI. However, after adjustment, the association with MND remained significant only among prefrail participants and no longer for frail persons (RR = 5.7, 95% CI 1.09 to 29.82; p = .039 and RR = 18.3, 95% CI 0.93 to 362.6; p = .056, respectively). DISCUSSION: Prefrailty is associated with symptomatic neurocognitive disorders in older adults living with HIV. The spectrum of the frailty phenotype in this already vulnerable population should serve as an indicator of concomitant cognitive decline.Read less <