Top

Published in:

01-02-2017

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

Authors: Kristen A. McLaurin, Rosemarie M. Booze, Charles F. Mactutus

Published in: Journal of NeuroVirology | Issue 1/2017

Abstract

Since the advent of combination antiretroviral therapy (cART), pediatric HIV-1 (PHIV) has evolved from a fatal disease to a chronic disease as children perinatally infected with HIV-1 survive into adulthood. The HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes constitutively throughout development, was used to model the early development of chronic neurological impairment in PHIV. Male and female Fischer HIV-1 Tg and F344 N 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). Later eye opening was observed in HIV-1 Tg animals relative to controls. HIV-1 Tg animals exhibited a shift in the development of locomotor activity implicating alterations in the maturation of the forebrain cholinergic inhibitory system. Alterations in the development of PPI and perceptual sharpening were observed in both auditory and visual PPI as indexed by a relative insensitivity to the dimension of time (msec for ISI; days of age for perceptual sharpening) as a function of the HIV-1 transgene. Presence of the HIV-1 transgene was diagnosed with 97.1 % accuracy using auditory and visual PPI measurements from PD 17 and 21. Early selective developmental alterations observed in the HIV-1 Tg rats provide an opportunity for the development of a point-of-care screening tool, which would permit the early diagnosis of PHIV and improve the long-term outcome for children perinatally infected with HIV-1.

Anday EK, Cohen ME, Kelley NE, Leitner DS (1989) Effect of in utero cocaine exposure on startle and its modification. Dev Pharmacol Ther 12:137–145PubMed

Aksenov MY, Aksenova MV, Nath A, Ray PD, Mactutus CF, Booze RM (2006) Cocaine-mediated enhancement of tat toxicity in rat hippocampal cell cultures: the role of oxidative stress and D1 dopamine receptor. Neurotoxicology 27:217–228CrossRefPubMed

Aksenov MY, Hasselrot U, Bansal AK, Wu G, Nath A, Anderson C, Mactutus CF, Booze RM (2001) Oxidative damage induced by the injection of HIV-1 tat protein in the rat striatum. Neurosci Lett 305:5–8CrossRefPubMed

Belman AL, Ultmann MH, Horoupian D, Novick B, Spiro AJ, Rubinstein A, Kurtzberg D, Cone-Wesson B (1985) Neurological complications in infants and children with acquired immune deficiency syndrome. Ann Neurol 18:560–566CrossRefPubMed

Blanchette N, Smith ML, King S, Fernandes-Penney A, Read S (2002) Cognitive development in school-age children with vertically transmitted HIV infection. Dev Neuropsychol 21:223–241CrossRefPubMed

Campbell BA, Lytle LD, Fibiger HC (1969) Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science 166:635–637CrossRefPubMed

Campbell BA, Mabry PD (1972) Ontogeny of behavioral arousal: a comparative study. J Comp Physiol Psychol 31:253–264

Cantó-Nogués C, Sánchez-Ramón S, Alvarez S, Lacruz C, Muñóz-Fernández MA (2005) HIV-1 infection of neurons might account for progressive HIV-1-associated encephalopathy in children. J Mol Neurosci 27:79–89CrossRefPubMed

Carter SL, Rourke SB, Murji S, Shore D, Rourke BP (2003) Cognitive complaints, depression, medical symptoms, and their association with neuropsychological functioning in HIV infection: a structural equation model analysis. Neuropsychology 17:410–419CrossRefPubMed

Cattie JE, Doyle K, Weber E, Grant I, Woods SP, the HIV Neurobehavioral Research Program (HNRP) Group (2012) Planning deficits in HIV-associated neurocognitive disorders: component processes, cognitive correlates, and implications for everyday functioning. J Clin Exp Neuropsyc 24:906–918CrossRef

Centers for Disease Control and Prevention (2013) Diagnosis of HIV infection in the United States and Dependent Areas (25). http://www.cdc.gov/hiv/pdf/g-l/hiv_surveillance_report_vol_25.pdf

Cherner M, Ellis RJ, Lazzaretto D, Young C, Mindt MR, Atkinson JH, Grant I, Heaton RK, the HNRC Group (2004) Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS 18:27–34CrossRef

Chiriboga CA, Fleishman S, Champion S, Gaye-Robinson L, Abrams EJ (2005) Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART). J Pediatr 146:402–407CrossRefPubMed

Cohen S, Caan MW, Mutsaerts HJ, Scherpbier HJ, Kuijpers TW, Reiss P, Majoie CB, Pajkrt D (2016) Cerebral injury in perinatally HIV-infected children compared to matched healthy controls. Neurology 86:19–27CrossRefPubMed

Corcoran S, Norrholm SD, Cuthbert B, Sternberg M, Hollis J, Duncan E (2011) Acoustic startle reduction in cocaine dependence persists for 1 year of abstinence. Psychopharmacology 215:93–103CrossRefPubMed

Crowell CS, Malee KM, Yogev R, Muller WJ (2014) Neurologic disease in HIV-infected children and the impact of combination antiretroviral therapy. Rev Med Virol 24:316–331CrossRefPubMed

Denenberg VH (1984) Some statistical and experimental considerations in the use of the analysis-of-variance procedure. Am J Physiol-Reg I 246:R403–R408

Edwards JK, Cole SR, Westreich D, Mugavero MJ, Eron JJ, Moore RD, Mathews WC, Hunt P, Williams C (2015) Age at entry into care, timing of antiretroviral therapy initiation, and 10-year mortality among HIV-seropositive adults in the United States. Clin Infect Dis 61:1189–1195CrossRefPubMedPubMedCentral

Efferen TR, Duncan EJ, Szilagyi S, Chakravorty S, Adams JU, Gonzenbach S, Angrist B, Butler PD, Rotrosen J (2000) Diminished acoustic startle in chronic cocaine users. Neuropsychopharmacology 22:89–96CrossRefPubMed

Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33–44CrossRefPubMed

Epstein LG, Sharer LR, Joshi VV, Fojas MM, Koenigsberger MR, Oleske JM (1985) Progressive encephalopathy in children with acquired immune deficiency syndrome. Ann Neurol 17:488–496CrossRefPubMed

Epstein LG, Sharer LR, Oleske JM, Connor EM, Goudsmit J, Bagdon L, Robert-Guroff M, Koenigsberger MR (1986) Neurologic manifestations of human immunodeficiency virus infection in children. Pediatrics 78:678–687PubMed

Ferguson G, Jelsma J (2009) The prevalence of motor delay among HIV infected children living in cape town, South Africa. Int J Rehabil Res 32:108–114CrossRefPubMed

Fibiger HC, Lytle LD, Campbell BA (1970) Cholinergic modulation of adrenergic arousal in the developing rat. J Comp Physiol Psychol 72:384–389CrossRefPubMed

Fitting S, Booze RM, Mactutus CF (2006a) Neonatal hippocampal tat injections: developmental effects on prepulse inhibition (PPI) of the auditory startle response. Int J Dev Neurosci 24:275–283CrossRefPubMedPubMedCentral

Fitting S, Booze RM, Mactutus CF (2006b) Neonatal intrahippocampal glycoprotein 120 injection: the role of dopaminergic alteration in prepulse inhibition in adult rats. J Pharmacol Exp Ther 318:1352–1358CrossRefPubMed

Fitting S, Booze RM, Mactutus CF (2008) Neonatal intrahippocampal injection of the HIV-1 proteins gp12 and tat: differential effects on behavior and the relationship to stereological hippocampal measures. Brain Res 1232:139–154CrossRefPubMedPubMedCentral

Fitting S, Booze RM, Mactutus CF (2015) HIV-1 proteins, tat and gp120, target the developing dopamine system. Curr HIV Res 13:21–42CrossRefPubMedPubMedCentral

Foster CJ, Biggs RL, Melvin D, Walters S, Tudor-Williams G, Lyall EGH (2006) Neurodevelopmental outcomes in children with HIV infection under 3 years of age. Dev Med Child Neurol 48:677–682CrossRefPubMed

Fournier P, Hebert S (2013) Gap detection deficits in humans with tinnitus as assessed with the acoustic startle paradigm: does tinnitus fill in the gap? Hear Res 295:16–23CrossRefPubMed

Franklin S, Lim HJ, Rennie KM, Eastwood D, Cuene B, Havens PL (2005) Longitudinal intellectual assessment of children with HIV infection. J Clin Psychol Med S 12:367–376CrossRef

Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ, Lee VM (2008) Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci 28:7687–7698CrossRefPubMedPubMedCentral

Gelman BB, Nguyen TP (2010) Synaptic proteins linked to HIV-1 infection and immunoproteasome induction: proteomic analysis of human synaptosomes. J NeuroImmune Pharmacol 5:92–102CrossRefPubMed

Greenhouse SW, Geisser S (1959) On methods in the analysis of profile data. Psychometrika 24:95–112CrossRef

Guillen S, Ramos JT, Resino R, Bellon JM, Munoz MA (2007) Impact on weight and height with the use of HAART in HIV-infected children. Pediatr Infect Dis J 26:334–338CrossRefPubMed

Hardy DJ, Hinkin CH, Levine AJ, Castellon SA, Lam MN (2006) Risky decision making assessed with the gambling task in adults with HIV. Neuropsychology 20:355–360CrossRefPubMedPubMedCentral

Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, The CHARTER Group (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy CHARTER study. Neurology 75:2087–2096CrossRefPubMedPubMedCentral

Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, LeBlanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Rivera-Mindt M, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, The CHARTER and HNRC Groups (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16CrossRefPubMed

Hinkin CH, Castellon SA, Hardy DJ, Granholm E, Siegle G (1999) Computerized and traditional Stroop task dysfunction in HIV-1 infection. Neuropsychology 13:306–316CrossRefPubMed

Hinkin CH, Castellon SA, Hardy DJ, Farinpour R, Newton T, Singer E (2001) Methylphenidate improves HIV-1-associated cognitive slowing. J Neuropsych Clin N 13:248–254CrossRef

Ison JR, Hammond GR (1971) Modification of startle reflex in rat by changes in auditory and visual environments. J Comp Physiol Psychol 75:435–452CrossRefPubMed

Kauffman WM, Sivit CJ, Fitz CR, Rakusan TA, Herzog K, Chandra RS (1992) CT and MR evaluation of intracranial involvement in pediatric HIV infection: a clinical-imaging correlation. Am J Neuroradiol 13:949–957PubMed

Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterline TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE, Crane HM, McKaig RG, Lau B, Freeman AM, Moore RD, Investigators NA-ACCORD (2009) Effect of early versus deferred antiretroviral therapy for HIV on survival. New Engl J Med 360:1815–1826CrossRefPubMedPubMedCentral

Kourtis AP, Bulterys M, Nesheim SR, Lee FK (2001) Understanding the timing of HIV transmission from mother to infant. JAMA-J Am Med Assoc 285:709–712CrossRef

Lee DE, Reid WC, Ibrahim WG, Peterson KL, Lentz MR, Maric D, Choyke PL, Jagoda EM, Hammoud DA (2014) Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV. Mol Imaging 13:1–10PubMed

Letendre SL, Ellis RJ, Everall I, Ances BM, Bharti A, McCutchan JA (2009) Neurologic complications of HIV disease and their treatment. Top HIV Med 17:46–56PubMedPubMedCentral

Lindsey JC, Malee KM, Brouwers P, Hughes MD (2007) Neurodevelopmental functioning in HIV-infected infants and young children before and after the introduction of protease inhibitor-based highly active antiretroviral therapy. Pediatrics 119:681–693CrossRef

Linn K, Fay A, Meddles K, Isbell S, Lin PN, Thair C, Heaps J, Paul R, Mar SS (2015) HIV-related cognitive impairment of orphans in Myanmar with vertically transmitted HIV taking antiretroviral therapy. Pediatr Neurol 53:485–491.e1CrossRefPubMed

Luzuriaga K, Mofenson LM (2016) Challenges in the elimination of pediatric HIV-1 infection. New Engl J Med 374:761–770CrossRefPubMed

Martin EM, Pitrak DL, Weddington W, Rains NA, Nunnally G, Nixon H, Grbesic S, Vassileva J, Bechara A (2004) Cognitive impulsivity and HIV serostatus in substance dependent males. J Int Neuropsych Soc 10:931–938

McArthur JC, Steiner J, Sacktor N, Nath A (2010) Human immunodeficiency virus-associated neurocognitive disorders mind the gap. Ann Neurol 67:699–714PubMed

McLaurin KA, Booze RM, Mactutus CF (2016) Minding the gap: progression of temporal processing deficits in the HIV-1 transgenic rat. To be presented at: International Society for Developmental Psychobiology, Nov 09–11, 2016, San Diego, CA

Minassian A, Henry BL, Woods SP, Vaida F, Grant I, Geyer MA, Perry W, Translational Methamphetamine AIDS Research Center (TMARC) Group (2013) Prepulse inhibition in HIV-associated neurocognitive disorders. J Int Neuropsych Soc 19:709–717CrossRef

Mintz M, Hoyt L, McSherry G, Mendelson J, Oleske J (1996) Levodopa therapy improves motor function in HIV-infected children with extrapyramidal syndromes. Neurology 47:1583–1585CrossRefPubMed

Moorcroft WH, Lytle LD, Campbell BA (1971) Ontogeny of starvation-induced behavioral arousal in the rat. J Comp Physiol Psychol 75:59–67CrossRefPubMed

Moran LM, Aksenov MY, Booze RM, Webb KM, Mactutus CF (2012) Adolescent HIV-1 transgenic rats: evidence for dopaminergic alterations in behavior and neurochemistry revealed by methamphetamine challenge. Curr HIV Res 10:415–424CrossRefPubMedPubMedCentral

Moran LM, Booze RM, Mactutus CF (2013a) Time and time again: temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat. J Neuroimmune Pharm 8:988–997CrossRef

Moran LM, Booze RM, Webb KM, Mactutus CF (2013b) Neurobehavioral alterations in HIV-1 transgenic rats: evidence for dopaminergic dysfunction. Exp Neurol 239:139–147CrossRefPubMed

Moran LM, Booze RM, Mactutus CF (2014a) Modeling deficits in attention, inhibition, and flexibility in HAND. J Neuroimmune Pharm 9:508–521CrossRef

Moran LM, Fitting S, Booze RM, Webb KM, Mactutus CF (2014b) Neonatal intrahippocampal HIV-1 protein Tat_1-86 injection: neurobehavioral alterations in the absence of increased inflammatory cytokine activation. Int J Dev Neurosci 38:195–203CrossRefPubMed

Parachure RS, Kulkarni VV, Darak TS, Mhaskar R, Miladinovic B, Emmanuel PJ (2015) Growth patterns of HIV infected Indian children in response to ART: a clinic based cohort study. Indian J Pediatr 82:519–524CrossRef

Paramesparan Y, Garvey LJ, Ashby J, Foster CJ, Fidler S, Winston A (2010) High rates of asymptomatic neurocognitive impairment in vertically acquired HIV-1-infected adolescents surviving into adulthood. JAIDS 55:134–136PubMed

Peng JS, Vigorito M, Liu XQ, Zhous DJ, Wu XW, Chang SL (2010) The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART. J Neuroimmunol 218:94–101CrossRefPubMed

Power C, Selnes OA, Grim JA, McArthur JC (1995) HIV dementia scale: a rapid screening test. J Acq Immune Def Synd 8:273–278CrossRef

Rao JS, Kim HW, Kellom M, Greenstein D, Chen M, Kraft AD, Harry GJ, Rapoport SI, Basselin M (2011) Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. J Neuroinflammation 8:101CrossRefPubMedPubMedCentral

Reid W, Sadowska M, Denaro F, Rao S, Foulke J, Hayes N, Jones O, Doodnauth D, Davis H, Sill A, O’Driscoll P, Huso D, Fouts T, Lewis G, Hill M, Kamin-Lewis R, Wei C, Ray P, Gallo RC, Reitz M, Bryant J (2001) An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. P Natl Acad Sci USA 98:9271–9276CrossRef

Roscoe RF Jr, Mactutus CF, Booze RM (2014) HIV-1 transgenic female rat: synaptodendritic alterations of medium spiny neurons in the nucleus accumbens. J NeuroImmune Pharmacol 9:642–653CrossRefPubMedPubMedCentral

Royal W, Zhang L, Guo M, Jones O, Davis H, Bryant JL (2012) Immune activation, viral gene product expression and neurotoxicity in the HIV-1 transgenic rat. J Neuroimmunol 247:16–24CrossRefPubMedPubMedCentral

Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, Robertson K, McArthur JC, Ronald A, Katabira E (2005) The international HIV dementia scale: a new rapid screening test for HIV dementia. AIDS 19:1367–1374PubMed

Schwartz L, Civitello L, Dunn-Pirio A, Ryschkewitsch S, Berry E, Cavert W, Kinzel N, Lawrence DMP, Hazra R, Major EO (2007) Evidence of human immunodeficiency virus type 1 infection of nestin-positive neural progenitors in archival pediatric brain tissue. J Neurovirol 13:274–283CrossRefPubMed

Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ (2013) Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol 106:1–16CrossRefPubMed

Shanbhag MC, Rutstein RM, Zaoutis T, Zhao H, Chao D, Radcliffe J (2005) Neurocognitive functioning in pediatric human immunodeficiency virus infection: effects of combined therapy. Arch Pediatr Adolesc Med 159:651–656CrossRefPubMed

Smith R, Wilkins M (2015) Perinatally acquired HIV infection: long-term neuropsychological consequences and challenges ahead. Child Neuropsychol 21:234–268CrossRefPubMed

Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37:510–518CrossRefPubMed

Tozzi V, Balestra P, Galgani S, Narciso P, Ferri F, Sebastiani GD, Amato C, Affricano C, Pigorini F, Pau FM, De Felici A, Benedetto A (1999) Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment. AIDS 13:1889–1897CrossRefPubMed

UNAIDS (2015) Fact sheet 2015. Retrieved from: http://www.unaids.org/en/resources/campaigns/HowAIDSchangedeverything/factsheet

Van Rie A, Harrington PR, Dow A, Robertson K (2007) Neurologic and neurodevelopmental manifestations of pediatric HIV/AIDS: a global perspective. Eur J Paediatr Neurol 11:1–9CrossRefPubMed

Van Rie A, Mupuala A, Dow A (2008) Impact of the HIV/AIDS epidemic on the neurodevelopment of preschool-aged children in Kinshasa, Democratic Republic of the Congo. Pediatrics 122:e123–e128CrossRefPubMedPubMedCentral

Vigorito M, Connaghan KP, Chang SL (2015) The HIV-1 transgenic rat model of neuroHIV. Brain Behav Immun 48:336–349CrossRefPubMedPubMedCentral

Walker SY, Pierre RB, Christie CD, Chang SM (2013) Neurocognitive function in HIV-positive children in a developing country. Int J Infect Dis 17:e862–e867CrossRefPubMed

Wears RL (2002) Advanced statistics: statistical methods for analyzing cluster and cluster-randomized data. Acad Emerg Med 9:330–341CrossRefPubMed

Webb KM, Aksenov MY, Mactutus CF, Booze RM (2010) Evidence for developmental dopaminergic alterations in the human immunodeficiency virus-1 transgenic rat. J Neurovirol 16:168–173CrossRefPubMedPubMedCentral

Whitehead N, Potterton J, Coovadia A (2014) The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care 26:497–504CrossRefPubMed

Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York

Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168CrossRefPubMedPubMedCentral

Zipursky AR, Gogolishvili D, Rueda S, Brunetta J, Carvalhal A, McCombe JA, Gill MJ, Rachlis A, Rosenes R, Arbess G, Marcotte T, Rourke SB (2013) Evaluation of brief screening tools for neurocognitive impairment in HIV/AIDS: a systematic review of the literature. AIDS 27:2385–2401CrossRefPubMedPubMedCentral

Title: Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1
Authors: Kristen A. McLaurin
Rosemarie M. Booze
Charles F. Mactutus
Publication date: 01-02-2017
Publisher: Springer International Publishing
Published in: Journal of NeuroVirology / Issue 1/2017
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-016-0476-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Long-term follow-up of HTLV-1 proviral load in asymptomatic carriers and in incident cases of HAM/TSP: what is its relevance as a prognostic marker for neurologic disease?

JC virus granule cell neuronopathy in the setting of chronic lymphopenia treated with recombinant interleukin-7

Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining “symptomatic” versus “asymptomatic” HAND

Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status

Evaluation of practice effect on neuropsychological measures among persons with and without HIV infection in northern India

Development and characterization of a human microglia cell model of HIV-1 infection