Selective Behavioral Alterations In The HIV-1 Transgenic Rat: Implications For Diagnosis Of Pediatric HIV-1

Since the advent of combination antiretroviral therapy (cART), pediatric HIV-1 (PHIV) has evolved from a fatal disease to a chronic disease with children perinatally infected with HIV-1 surviving into adulthood. The HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes constitutively throughout development, was used to investigate the early development of chronic neurological impairment in PHIV. Male and female Fischer HIV-1 Tg and F344N control rats, sampled from 35 litters, were repeatedly assessed during early development using multiple experimental paradigms, including somatic growth, locomotor activity, cross-modal prepulse inhibition (PPI) and gap-prepulse inhibition (gap-PPI). A rightward shift towards later eye opening was observed in HIV-1 Tg animals in comparison to controls. HIV-1 Tg animals exhibited delays in the development of the cholinergic inhibitory system, assessed using locomotor activity. Alterations in the development of the interstimulus interval (ISI) function were observed in HIV-1 Tg rats in comparison to control animals, assessed using PPI. Presence of the HIV-1 transgene was diagnosed with 91.4% accuracy using multiple behavioral assessments on PD 20 and 21. Selective early behavioral alterations observed in the HIV-1 Tg rats provide an opportunity for the development of a clinical diagnostic screening tool, which may improve the long-term outcome for children perinatally infected with HIV-1