The expression of cognitive symptoms associated with HIV varies over time and across individuals. This pattern may reflect transient contextual factors, including the degree of effort exerted by individuals undergoing cognitive testing. The present study examined whether effort corresponds to the expression of persistent HIV-related cognitive impairment among individuals receiving combination antiretroviral therapy (cART). HIV+ individuals (n = 111) averaged 48.2 (14.9) years of age and 13.0 (2.7) years of education and HIV- individuals (n = 92) averaged 34.9 (17.2) years of age and 13.5 (1.9) years of education. Participants completed a neuropsychological battery and a clinically validated measure of effort (Test of Memory Malingering, trial 1). Results revealed that the vast majority of HIV+ (85%) and HIV- (89%) individuals performed above published guidelines for adequate effort. Furthermore, the expression of cognitive impairment in HIV was not related to effort performance. The results were unchanged when examining HIV+ individuals with and without viral suppression. Finally, disability and disability-seeking status, and a proxy measure of apathy did not correspond to effort levels in HIV+ individuals. These findings suggest that variability in the expression of cognitive impairment in the cART era is unlikely to represent overt effort failures or other confounds unrelated to the disease. Persistent cognitive impairment in HIV likely represents historical and/or ongoing disease mechanisms despite otherwise successful treatment.

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine astrocytes, as well as patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we further show that sex differences in p21-induced senescence are patterned during early development by gonadal sex. These data provide a rationale for the further study of sex differences in radiation response and how senescence might be enhanced for radiation sensitization. The determination that p21 and gonadal sex are required for sex differences in radiation response will serve as a foundation for these future mechanistic studies.