Sleep Profile and Self-Reported Neuropsychiatric Symptoms in Vertically HIV-Infected Adolescents on cART

Abstract

Background Sleep quality (SQ) data in human immunodeficiency virus (HIV) pediatric population are scarce. Our main objective was to assess SQ in our cohort and to determine the impact of antiretroviral therapy (ART) on sleep in a cohort of HIV-infected adolescents on cART.

Materials and Methods The SQ was assessed through the Pittsburgh Sleep Quality Index (PSQI). Neuropsychiatric symptoms (NS) were recorded using an auto-administered questionnaire. To determine the antiretroviral (ARV) impact of efavirenz (EFV) on SQ, patients on EFV versus protease inhibitors-based regimens were compared.

Results Forty-six patients were evaluated (median age: 16 years, interquartile range [IQR]: 10.8, 17)). Age at the start of ART: 1.3 years (0.4, 5.2); 23.9% showed acquired immunodeficiency syndrome (AIDS) category. Median CD4 at baseline was 656 (550, 808) cells/mm³; 91.3% had viral load <50 copies/mL. Median time on cART was 11.3 years (7.5, 15.2). Fifty-two percent of the patients were on EFV-based regimen. No differences were found in clinical and immunovirological variables although patients on EFV were older and were exposed for a longer time to ARV. Poor SQ was found in 26.1% of patients. Most frequent complaints were: sleep disturbances (76.1%), sleep latency (63%), and daytime dysfunction (54.3%). Similarly, there were no significant differences in NS between both treatment groups according to patients' reports but were significantly more common in bad sleepers. Patients on EFV-based regimen were more likely to repeat one or more school grades after the adjustment for age at evaluation and nadir CD4 percentage (odds ratio [OR]: 14.421, confidence interval [CI] 95%: 1.207–172.249, p = 0.035).

Conclusions Sleep complaints and NS are common among our cohort of HIV adolescents on long-term cART and interestingly, not only in those who were receiving EFV.

Keywords

perinatal HIV infection - adolescents - sleep quality - antiretrovirals - neuropsychiatric symptoms

Financial Disclosure

Authors declare have no financial relationships relevant to this article to disclose.

Appendix of Additional Study Sites and Participants

NeuroCoRISpe project: María Isabel González-Tomé, Pablo Rojo, Daniel Blázquez, Elisa Fernández Cooke, Cristina Epalza, Luis Prieto, Berta Zamora, Cristina García-Navarro, Manuela Martin-Bejarano, Carlos Velo, and Ana Martínez de Aragón (Hospital Doce de Octubre, Madrid); María José Mellado, Luis Escosa, Milagros García Hortelano, and Talía Sainz (Hospital La Paz); José Tomás Ramos and Isabel Cuéllar (Hospital Clínico San Carlos, Madrid); Sara Guillén (Hospital de Getafe); María Luisa Navarro, Jesús Saavedra, Mar Santos, Ma AngelesMuñoz-Fernández, Beatriz Ruiz-Saez, Carolina Fernandez McPhee, Santiago Jiménez de Ory, Susana Álvarez, and Ignacio Rodriguez Izquierdo (Hospital Gregorio Marañón); Claudia Fortuny and Ton Noguera (Hospital Sant Joan de Deu); David Moreno and Esmeralda Núñez (Hospital Carlos Haya); and Olaf Neth and Dolores Falcón (Hospital Virgen del Rocío). This project is included in CoRISpe Cohort Working Group (AIDS Paed Research network): María José Mellado, Luis Escosa, Milagros García Hortelano, Talía Sainz (Hospital La Paz); María Isabel González-Tomé, Pablo Rojo, Daniel Blázquez, Cristina Epalza (Hospital Doce de Octubre, Madrid); José Tomás Ramos (Hospital Clínico San Carlos, Madrid); Luis Prieto, Sara Guillén (Hospital de Getafe); María Luisa Navarro, Jesús Saavedra, Mar Santos, Ma Angeles Muñoz, Beatriz Ruiz, Carolina Fernandez McPhee, Santiago Jimenez de Ory, Itzíar Carrasco, (Hospital Gregorio Marañón); Miguel Ángel Roa (Hospital de Móstoles); José Beceiro, María Penín (Hospital Príncipe de Asturias, Alcalá de Henares); Jorge Martínez (Hospital Niño Jesús, Madrid); Katie Badillo (Hospital de Torrejón); Miren Apilanez (Hospital de Donostia, San Sebastián); Itziar Pocheville (Hospital de Cruces, Bilbao); Elisa Garrote (Hospital de Basurto, Bilbao); Elena Colino (Hospital Insular Materno Infantil, Las Palmas de Gran Canaria); Jorge Gómez Sirvent (Hospital Virgen de la Candelaria, Santa Cruz de Tenerife); Mónica Garzón, Vicente Román (Hospital de Lanzarote); María José Muñoz, Raquel Angulo (Hospital de Poniente, El Ejido); Olaf Neth, Lola Falcón (Hospital Virgen del Rocio, Sevilla); Pedro Terol (Hospital Virgen de la Macarena, Sevilla); Juan Luis Santos (Hospital Virgen de las Nieves, Granada); David Moreno (Hospital Carlos Haya, Málaga); Francisco Lendínez (Hospital de Torrecárdenas, Almería); Ana Grande (Complejo Hospitalario Universitario Infanta Cristina, Badajoz); Francisco José Romero (Complejo Hospitalario de Cáceres); Carlos Pérez (Hospital de Cabueñes, Gijón); María Martínez (Hospital Universitario Central de Asturias); Miguel Lillo (Hospital de Albacete); Begoña Losada (Hospital Virgen de la Salud, Toledo); Mercedes Herranz (Hospital Virgen del Camino, Pamplona); Matilde Bustillo, Carmelo Guerrero (Hospital Miguel Servet, Zaragoza); Pilar Collado (Hospital Clínico Lozano Blesa, Zaragoza); José Antonio Couceiro (Complejo Hospitalario de Pontevedra); Leticia Vila (Complejo Hospitalario Universitario La Coruña); Consuelo Calviño (Hospital Universitario Lucus Augusti de Lugo); Ana Isabel Piqueras, Rafael Bretón, Inmaculada Segarra (Hospital La Fe, Valencia); César Gavilán (Hospital San Juan de Alicante); Elena Montesinos (Hospital General de Valencia); Marta Dapena (Hospital de Castellón); Cristina Álvarez, Beatriz Jiménez (Hospital Marqués de Valdecilla, Santander); Ana Gloria Andrés (Hospital de León); Víctor Marugán, Carlos Ochoa (Hospital de Zamora); Santiago Alfayate, Ana Isabel Menasalvas (Hospital Virgen de la Arrixaca, Murcia); Yolanda Ruiz del Prado (Complejo Hospitalario San Millán-San Pedro, Logroño) and Paediatric HIV-BioBank integrated in the Spanish AIDS Research Network and collaborating Centers.

• References

• 1 Reid S, Dwyer J. Insomnia in HIV infection: a systematic review of prevalence, correlates, and management. Psychosom Med 2005; 67 (02) 260-269
• 2 Allavena C, Guimard T, Billaud E. , et al. Prevalence and risk factors of sleep disturbances in a large HIV-infected adult population. J Int AIDS Soc 2014; 17 (04) (Suppl. 03) 19576
• 3 Hysing M, Harvey AG, Linton SJ, Askeland KG, Sivertsen B. Sleep and academic performance in later adolescence: results from a large population-based study. J Sleep Res 2016; 25 (03) 318-324
• 4 Franck LS, Johnson LM, Lee K. , et al. Sleep disturbances in children with human immunodeficiency virus infection. Pediatrics 1999; 104 (05) e62
• 5 Gazini CC, Reimão RN, Rossini SR. , et al. Quality of sleep and quality of life in adolescents infected with human immunodeficiency virus. Arq Neuropsiquiatr 2012; 70 (06) 422-427
• 6 Moyle G, Fletcher C, Brown H, Mandalia S, Gazzard B. Changes in sleep quality and brain wave patterns following initiation of an efavirenz-containing triple antiretroviral regimen. HIV Med 2006; 7 (04) 243-247
• 7 Gallego L, Barreiro P, del Río R. , et al. Analyzing sleep abnormalities in HIV-infected patients treated with Efavirenz. Clin Infect Dis 2004; 38 (03) 430-432
• 8 Núñez M, González de Requena D, Gallego L, Jiménez-Nácher I, González-Lahoz J, Soriano V. Higher efavirenz plasma levels correlate with development of insomnia. J Acquir Immune Defic Syndr 2001; 28 (04) 399-400
• 9 Clifford DB, Evans S, Yang Y. , et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med 2005; 143 (10) 714-721
• 10 Lochet P, Peyrière H, Lotthé A, Mauboussin JM, Delmas B, Reynes J. Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Med 2003; 4 (01) 62-66
• 11 Blanch J, Martínez E, Rousaud A. , et al. Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz. J Acquir Immune Defic Syndr 2001; 27 (04) 336-343
• 12 Gutiérrez F, Navarro A, Padilla S. , et al. Prediction of neuropsychiatric adverse events associated with long-term efavirenz therapy, using plasma drug level monitoring. Clin Infect Dis 2005; 41 (11) 1648-1653
• 13 Fumaz CR, Muñoz-Moreno JA, Moltó J. , et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. J Acquir Immune Defic Syndr 2005; 38 (05) 560-565
• 14 Muñoz-Moreno JA, Fumaz CR, Ferrer MJ. , et al. Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates, and management. A neurobehavioral review. AIDS Rev 2009; 11 (02) 103-109
• 15 Chee MW, Choo WC. Functional imaging of working memory after 24 hr of total sleep deprivation. J Neurosci 2004; 24 (19) 4560-4567
• 16 Gamaldo CE, Gamaldo A, Creighton J. , et al. Evaluating sleep and cognition in HIV. J Acquir Immune Defic Syndr 2013; 63 (05) 609-616
• 17 Steenari M-R, Vuontela V, Paavonen EJ, Carlson S, Fjallberg M, Aronen E. Working memory and sleep in 6- to 13-year-old schoolchildren. J Am Acad Child Adolesc Psychiatry 2003; 42 (01) 85-92
• 18 Liu J, Liu X, Ji X, Wang Y, Zhou G, Chen X. Sleep disordered breathing symptoms and daytime sleepiness are associated with emotional problems and poor school performance in children. Psychiatry Res 2016; 242: 218-225
• 19 Urrila AS, Artiges E, Massicotte J. , et al; IMAGEN consortium. Sleep habits, academic performance, and the adolescent brain structure. Sci Rep 2017; 7: 41678
• 20 Touchette E, Petit D, Séguin JR, Boivin M, Tremblay RE, Montplaisir JY. Associations between sleep duration patterns and behavioral/cognitive functioning at school entry. Sleep 2007; 30 (09) 1213-1219
• 21 Nixon GM, Thompson JM, Han DY. , et al. Short sleep duration in middle childhood: risk factors and consequences. Sleep 2008; 31 (01) 71-78
• 22 Danner F, Phillips B. Adolescent sleep, school start times, and teen motor vehicle crashes. J Clin Sleep Med 2008; 4 (06) 533-535
• 23 Sadeh A, Gruber R, Raviv A. The effects of sleep restriction and extension on school-age children: what a difference an hour makes. Child Dev 2003; 74 (02) 444-455
• 24 de Jose MI, Jiménez de Ory S, Espiau M. , et al; working groups of CoRISpe and HIV HGM BioBank. A new tool for the paediatric HIV research: general data from the Cohort of the Spanish Paediatric HIV Network (CoRISpe). BMC Infect Dis 2013; 13: 2
• 25 Rojas Sánchez P, Prieto L, Jiménez De Ory S. , et al; Madrid Cohort of HIV-1 Infected Children and Adolescents Integrated in the Paediatric Branch of the Spanish National AIDS Network (CoRISPe). Impact of lopinavir-ritonavir exposure in HIV-1 infected children and adolescents in Madrid, Spain during 2000-2014. PLoS One 2017; 12 (03) e0173168
• 26 Medin G, García-Navarro C, Navarro Gomez M. , et al. Disease disclosure, treatment adherence, and behavioural profile in a cohort of vertically acquired HIV-infected adolescents. NeuroCoRISpeS study. AIDS Care 2016; 28 (01) 124-130
• 27 García-Navarro C, García I, Medín G. , et al. Psychosocial aspects in a cohort of vertically transmitted human immunodeficiency virus-infected adolescents [article in Spanish]. Enferm Infecc Microbiol Clin 2014; 32 (10) 631-637
• 28 García-Navarro C, Jiménez de Ory S, Navarro Gómez M. , et al; Research Group CoRISpeS-Madrid cohort. Sleep disturbances in a cohort of HIV-infected children and adolescents on antiretroviral treatment. NeuroCoRISpeS. (CROI Abstract 937) In Special Issue: Abstracts From the 2015 Conference on Retroviruses and Opportunistic Infections. Top Antivir Med 2015; 23 (e-1): 432-433
• 29 Buysse DJ, Reynolds III CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28 (02) 193-213
• 30 Macías Fernández JA, Royuela Rico A. La versión española del índice de calidad de sueño de Pittsburgh. Inform Psiquiátricas 1996; 146: 465-472
• 31 Kaufman A, Kaufman N. . K-BIT Test Breve de Inteligencia [K-BIT. Kaufman Brief Intelligence Test]. Madrid: TEA; 1997
• 32 Sivertsen B, Glozier N, Harvey AG, Hysing M. Academic performance in adolescents with delayed sleep phase. Sleep Med 2015; 16 (09) 1084-1090
• 33 Carskadon MA. Sleep in adolescents: the perfect storm. Pediatr Clin North Am 2011; 58 (03) 637-647
• 34 Moore M, Meltzer LJ. The sleepy adolescent: causes and consequences of sleepiness in teens. Paediatr Respir Rev 2008; 9 (02) 114-120 , quiz 120–121
• 35 Sivertsen B, Harvey AG, Reichborn-Kjennerud T, Torgersen L, Ystrom E, Hysing M. Later emotional and behavioral problems associated with sleep problems in toddlers: a longitudinal study. JAMA Pediatr 2015; 169 (06) 575-582
• 36 O'Brien LM. The neurocognitive effects of sleep disruption in children and adolescents. Child Adolesc Psychiatr Clin N Am 2009; 18 (04) 813-823
• 37 Gruber R, Laviolette R, Deluca P, Monson E, Cornish K, Carrier J. Short sleep duration is associated with poor performance on IQ measures in healthy school-age children. Sleep Med 2010; 11 (03) 289-294
• 38 Allavena C, Guimard T, Billaud E. , et al; COREVIH-Pays de la Loire Troubles du Sommeil Study Group. Prevalence and risk factors of sleep disturbance in a large HIV-infected adult population. AIDS Behav 2016; 20 (02) 339-344
• 39 Brahmbhatt H, Boivin M, Ssempijja V. , et al. Impact of HIV and atiretroviral therapy on neurocognitive outcomes among school-aged children. J Acquir Immune Defic Syndr 2017; 75 (01) 1-8
• 40 Ellis RJ, Badiee J, Vaida F. , et al; CHARTER Group. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 2011; 25 (14) 1747-1751
• 41 Heaton RK, Franklin DR, Ellis RJ. , et al; CHARTER Group; HNRC Group. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 2011; 17 (01) 3-16
• 42 Muñoz-Moreno JA, Pérez-Álvarez N, Muñoz-Murillo A. , et al. Classification models for neurocognitive impairment in HIV infection based on demographic and clinical variables. PLoS One 2014; 9 (09) e107625
• 43 van den Dries LWJ, Wagener MN, Jiskoot LC. , et al. Neurocognitive impairment in a chronically well-suppressed HIV-infected population: the Dutch TREVI Cohort Study. AIDS Patient Care STDS 2017; 31 (08) 329-334
• 44 Judd A, Le Prevost M, Melvin D. , et al; Adolescents and Adults Living With Perinatal HIV (AALPHI) Steering Committee. Cognitive function in young persons with and without perinatal HIV in the AALPHI Cohort in England: role of non-HIV-related factors. Clin Infect Dis 2016; 63 (10) 1380-1387
• 45 Cohen S, Ter Stege JA, Geurtsen GJ. , et al. Poorer cognitive performance in perinatally HIV-infected children versus healthy socioeconomically matched controls. Clin Infect Dis 2015; 60 (07) 1111-1119