Abstract
Sex differences in human immunodeficiency virus type-1 (HIV-1) have been repeatedly suggested. Females, who account for 51% of HIV-1 seropositive individuals, are inadequately represented in clinical and preclinical studies, as well as in the description of HIV-1 associated neurocognitive disorders (HAND). Direct comparisons of neurocognitive decline in women and men must be made to address this underrepresentation. The effect of biological sex (i.e., the biological factors, including chromosomes and hormones, determining male or female characteristics; WHO, 2017) on sustained attention, which is commonly impaired in HIV-1 seropositive individuals, was investigated in intact HIV-1 transgenic (Tg) and control animals using a signal detection operant task. Analyses revealed a robust sex difference in the rate of task acquisition, collapsed across genotype, with female animals meeting criteria in shaping (at least 60 reinforcers for three consecutive or five non-consecutive sessions) and signal detection (70% accuracy for five consecutive or seven non-consecutive sessions) significantly more slowly than male animals. Presence of the HIV-1 transgene also had a significant effect on shaping and signal detection acquisition, with HIV-1 Tg animals displaying significant deficits in the rate of acquisition relative to control animals–deficits that were more prominent in female HIV-1 Tg animals. Once the animals’ reached asymptotic performance in the signal detection task, female animals achieved a lower percent accuracy across test sessions and exhibited a decreased response rate relative to male animals, although there was no compelling evidence for any effect of transgene. Results indicate that the factor of biological sex may be a moderator of the influence of the HIV-1 transgene on signal detection. Understanding the impact of biological sex on neurocognitive deficits in HIV-1 is crucial for the development of sex-based therapeutics and cure strategies.
Highlights
Sex differences in human immunodeficiency virus type-1 (HIV-1) have been reported in studies conducted both before (e.g., Melnick et al, 1994) and after the advent of combination antiretroviral therapy
A signal detection operant task was conducted to examine the effect of biological sex on sustained attention deficits in the HIV-1 Tg rat
Presence of the HIV-1 transgene had a significant effect on the temporal process of task acquisition in female, but not male, animals
Summary
Sex differences in human immunodeficiency virus type-1 (HIV-1) have been reported in studies conducted both before (e.g., Melnick et al, 1994) and after the advent of combination antiretroviral therapy (cART; e.g., Hestad et al, 2012; Griesbeck et al, 2016; Royal et al, 2016). Women represent a larger population of individuals living with HIV-1, they are inadequately represented in the reports of both clinical and preclinical studies, as well as in the description of HIV-1 associated neurocognitive disorders (HAND; Maki and Martin-Thormeyer, 2009), characterized by deficits in executive function, attention and memory (Cysique et al, 2004; Heaton et al, 2011; Sacktor and Robertson, 2014). A pilot study in Zambia, Africa revealed that HIV-1 seropositive women exhibited greater neurocognitive deficits in comparison to HIV-1 seropositive men (Hestad et al, 2012). More recent clinical studies, conducted in Nigeria, more definitively revealed differential neurocognitive impairment for HIV-1 seropositive women and men (Royal et al, 2016). HIV-1 seropositive women, relative to HIV-1 seropositive men, were significantly more impaired on measures of speed of information processing, verbal fluency, learning and memory; deficits which were correlated with higher levels of monocytes (Royal et al, 2016)
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