Accessibility / Report Error

Audiological assessment of children with HIV/AIDS: a meta-analysis Please cite this article as: Bentivi JO, Azevedo CM, Lopes MK, Rocha SC, Silva PC, Costa VM, et al. Audiological assessment of children with HIV/AIDS: a meta-analysis. J Pediatr (Rio J). 2020;96:537-45. , ☆☆ ☆☆ Study conducted at Federal University of Maranhão, São Luís, MA, Brazil.

Abstract

Objective:

To analyze the results of the audiological evaluation of children with HIV and AIDS.

Data collection:

Systematic review carried out in May 2019 in the Web of Science, PubMed, SciELO, and Scopus databases. Case reports and original articles were included, with no limitationsregarding country or year of publication.

Data synthesis:

278 articles were identified; 26 were included, in which HIV/AIDS was shown to be a risk factor for hearing loss (OR = 5.364; p = 0.00). The studies used different audiological exams, with varying methodologies. There was no difference regarding the type of hearing loss (p = 0.119).

Conclusion:

Longitudinal studies using the same type of examination at all stages are suggested, to allow better monitoring of the effects of HIV on the child's hearing,and studies that provide more methodological details. The knowledge of the influence of HIV on the child's auditory system may lead to the promotion of measures that minimize the prevalence of hearing loss, allow an early diagnosis and timely rehabilitation, so as not to compromise child development.

KEYWORDS
Human immunodeficiency virus; AIDS; Audiology; Hearing loss

Resumo

Objetivo:

Analisar os resultados da avaliação audiológica de crianças com HIV e AIDS.

Coleta dos dados:

Revisão sistemática realizada em maio de 2019 nas bases Web of Science, Pubmed, SciELO e Scopus. Relatos de caso e artigos originais foram incluídos, sem limitação quanto ao país ou ano de publicação.

Síntese dos dados:

Foram identificados 278 artigos, sendo que 26 foram incluídos, nos quais o HIV/AIDS foi mostrado como fator de risco para perda auditiva (OR = 5.364; p = 0.00). Os estudos utilizaram diferentes exames audiológicos, com diferentes metodologias. Não houve diferença com relação ao tipo de perda auditiva (p = 0.119).

Conclusão:

Sugere-se estudos longitudinais usando o mesmo tipo de exame em todas as fases para possibilitar melhor acompanhamento dos efeitos do HIV na audição da criança e estudos que tragam mais detalhes metodológicos. O conhecimento da influência do HIV no sistema auditivo infantil pode levar à promoção de medidas que minimizem a prevalência da perda auditiva, possibilitem diagnóstico precoce e permita reabilitação em tempo hábil para não comprometer o desenvolvimento infantil.

PALAVRAS-CHAVE
Vírus da imunodeficiência humana; AIDS; Audiologia; Perda auditiva

Introduction

HIV infection leads to the progressive impairment of the affected individuals' immunity. With the advent of antiretroviral therapy (ART), the survival of these patients has been prolonged and, consequently, there has been an increase in the spectrum of acute and chronic diseases, especially airway infections such as otitis. 11 Matas CG, Angrisani RG, Magliaro FC, Segurado AA. Audiological manifestations in HIV-positive adults. Clinics (Sao Paulo). 2014;69:469-75.

2 Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65.
- 33 Sanjar FA, Queiroz BE, Miziara ID. Otolaryngologic manifestations in HIV disease - clinical aspects and treatment. Braz J Otorhinolaryngol. 2011;77:391-400.

Otitis media can cause hearing loss and be the main cause of impairment in people with HIV/AIDS, especially in childhood, the age group most often affected by upper airway infections. 11 Matas CG, Angrisani RG, Magliaro FC, Segurado AA. Audiological manifestations in HIV-positive adults. Clinics (Sao Paulo). 2014;69:469-75., 22 Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65., 44 Matas CG, Leite RA, Magliaro FC, Gonçalves IC. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS). Braz J Infect Dis. 2006;10:264-8. However, hearing loss related to sensory or neural damage (direct damage by opportunistic infections or neuropathy) has also been observed. 55 Christopher N, Edward T, Sabrina BK, Agnes N. The prevalence of hearing impairment in the 6 months - 5 years HIV/AIDS-positive patients attending paediatric infectious disease clinic at Mulago Hospital. Int J Pediatr Otorhinolaryngol. 2013;77:262-5., 66 Matas CG, Iorio MC, Succi RC. Auditory disorders and acquisition of the ability to localize sound in children born to HIV-positive mothers. Braz J Infect Dis. 2008;12:10-4. It is estimated that 20-50% of people with HIV/AIDS have different degrees of sensorineural hearing loss, and this type is more prevalent among adults than in children. 11 Matas CG, Angrisani RG, Magliaro FC, Segurado AA. Audiological manifestations in HIV-positive adults. Clinics (Sao Paulo). 2014;69:469-75.

The association between HIV/AIDS and hearing loss requires further study, as the literature shows conflicting findings, particularly those related to the type of loss caused by the disease. Nonetheless, HIV/AIDS is recognized as a risk factor for hearing impairment. 77 Lewis DR, Marone SA, Mendes BC. Multiprofessional committee on auditory healthy: COMUSA. Braz J Otorhinolaryngol. 2010;76:121-8. However, there are few studies that consider the association between auditory findings and clinical and laboratory characteristics of the infection (viral load and CD4+ and CD8+Tlymphocyte counts) or the effects of ART. 33 Sanjar FA, Queiroz BE, Miziara ID. Otolaryngologic manifestations in HIV disease - clinical aspects and treatment. Braz J Otorhinolaryngol. 2011;77:391-400., 88 Olusanya BO, Neumann KJ, Saunders JE. The global burden of disabling hearing impairment: a call to action. Bull World Health Organ. 2014;92:367-73., 99 Olusanya BO, Solanke OA. Maternal and neonatal factors associated with mode of delivery under a universal newborn hearing screeningprogramme in Lagos, Nigeria. BMC Pregnancy Childbirth. 2009;9:41.

HIV, AIDS, or ART-related hearing sequelae can be better understood by analyzing studies with the pediatric population, as confounding factors could be minimized, such as the effects of chronic exposure to high sound pressure levels, effects of senility, and use of non-ART-related ototoxic medications. 1010 Kallail KJ, Downs DW, Scherz JW. Communication disorders in individuals with HIV/AIDS. Kansas J Med. 2008;1:62-9.

As the integrity of the peripheral and central auditory system is essential for adequate language and learning development, it is necessary to better understand the effects of HIV on children's hearing loss to establish preventive measures and implement early diagnosis and rehabilitation measures, to reduce the limitations caused by this impairment. 44 Matas CG, Leite RA, Magliaro FC, Gonçalves IC. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS). Braz J Infect Dis. 2006;10:264-8., 1111 Assuiti LF, Lanzoni GM, Santos FC, Erdmann AL, Meirelles BH. Hearing loss in people with HIV/AIDS and associated factors: an integrative review. Braz J Otorhinolaryngol. 2013;79:248-55.

For this reason, the present study was proposed to analyze the results of the hearing assessment of children with HIV and AIDS available in the literature.

Data collection

In May 2019, a systematic review of audiological findings in children with HIV and AIDS was performed through a literature search in the Web of Science, PubMed, SciELO, and Scopus databases. Studies were not limited regarding the country or year of publication.

The primary sought outcomes were: (1) the odds ratio (OR) and relative risk (RR) for hearing loss in patients with HIV; (2) the association between hearing loss and HIV status; and (3) the otoscopy performed before audiological examinations.

The keywords used in the research were the MeSH (medical subjective headings) descriptors "HIV" AND "hearing" AND "children OR childhood." Case reports and prospective or retrospective studies on the association between HIV infection and audiological findings were included in the review. Exclusion criteria were as follows: literature reviews, short communications, abstracts from articles presented at congresses, editorials, studies not written in English or Portuguese, articles including children with HIV and other co-infections, studies on neonatal screening, articles without information regarding which audiological examinations were performed, and abstracts that were not related to the objective of this review.

The search resulted in 445 citations, narrowed to 278 articles after removing duplicates. The authors then excluded 205 articles after reading the abstracts, nine articles because of the language, and 22 articles due to the type of study, in that order. Finally, 26 articles were selected according to the established inclusion and exclusion criteria, after an independent analysis by the two authors and the opinion of a third author, in case of divergence (Fig. 1).

Figure 1
Decision-making process of the articles included in this study. Adapted from Moher et al. 1212 Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000098..

The articles were assessed regarding the number of studied children with HIV, children's age, performed audiological exams, otoscopy findings, use of ART, CD4+ T-cell count, and viral load.

The methodological guidelines and checklist established by PRISMA 1212 Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000098. were followed. The quality assessment of the elected articles was performed using the modified version of the Quality Assessment Tool for Systematic Reviews of Observational Studies (QATSO). 1313 Wong WC, Cheung CS, Hart GJ. Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours. Emerg Themes Epidemiol. 2008;5:23. The used criteria were as follows: measure objectivity, validation of performed audiological examinations, and probabilistic sample (except for case reports).

The data were exported to STATA 12.0 (Stata Statistical Software: Release 12. College Station, TX, USA) software for analysis. The random effect meta-analysis was performed after the heterogeneity tests were calculated using the Mantel-Haenszel method. Nonexistent values (for studies that did not use a control group) were eliminated to maximize statistical power. Due to the sample discrepancy between studies, square root transformation to OR was used to minimize the risk of statistical bias. OR and RR for hearing loss in children with HIV/AIDS were calculated.

Data synthesis

The quality assessment of the articles found that all selected studies included validated examinations and objective measures of auditory investigation. However, none of them used a probabilistic sample.

Exams performed

Summaries of the exams performed are shown in Table 1. In total, five studies showed that only one type of audiological exam was performed, 1414 Torre P, Yao TJ, Zeldow B, Williams P, Hoffman HJ, Siberry GK. Distortion product otoacoustic emission data in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents in the pediatric HIV/AIDS cohort study. Pediatr Infect Dis J. 2015;34:276-8.

15 Govender R, Eley B, Walker K, Petersen R, Wilmshurst JM. Neurologic and neurobehavioral sequelae in children with human immunodeficiency virus (HIV-1) infection. J Child Neurol. 2011;26:1355-64.

16 Nakku D, Nyaiteera V, Llowet E, Nanseera D, Nakalema G, Westerberg B, et al. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in South Western Uganda. Int J Pediatr Otorhinolaryngol. 2017;101:172-7.

17 Chidziva C, Matsekete J, Bandason T, Shamu S, Dzongodza T, Matinhira N. Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe. Cent Afr J Med. 2015;61:56-61.
- 1818 Smith AF, Ianacone DC, Ensink RJ, Melaku A, Casselbrant ML, Isaacson G. Prevalence of hearing-loss among HAART-treated children in the Horn of Africa. Int J Pediatr Otorhinolaryngol. 2017;98:166e170. 19 used conventional or conditioned pure tone audiometry (depending on the child's age), eight used the auditory brainstem response (ABR) (especially in younger children), and eight used conventional tests. Some authors reported vocal audiometry (mainly hearing discrimination tests). 1919 Palacios GC, Montalvo MS, Fraire MI, Leon E, Alvarez MT, Solorzano F. Audiologic and vestibular findings in a sample of human immunodeficiency virus type-1-infected Mexican children under highly active antiretroviral therapy. Int J Pediatr Otorhinolaryngol. 2008;72:1671-81.

20 Makar SK, Dhara S, Sinha AK, Chatterjee I, Dutta P. Nature and onset of communication disorder in pediatrics with HIV. Int J Ped Otorhinolaryngol. 2012;76:1065-6.
- 2121 Matas CG, Sansone AP, Iorio MC, Succi RC. Avaliação Audiológica emcrianças nascidas de mãessoropositivas para o vírus da imunodeficiênciahumana. Braz J Otorhinolaryngol. 2000;66:317-24. Seven studies used otoacoustic emissions (OAE) test, of which four were the distortion product type 1414 Torre P, Yao TJ, Zeldow B, Williams P, Hoffman HJ, Siberry GK. Distortion product otoacoustic emission data in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents in the pediatric HIV/AIDS cohort study. Pediatr Infect Dis J. 2015;34:276-8., 2222 Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51.

23 Torre P, Cook A, Elliott H, Dawood G, Laughton B. Hearing assessment data in HIV-infected and uninfected children of Cape Town, South Africa. AIDS Care. 2015;27:1037-41.
- 2424 Knox J, Arpadi SM, Kauchali S, Craib M, Kvalsvig JD, Taylor M, et al. Screening for developmental disabilities in HIV positive and HIV negative children in South Africa: results from the Asenze Study. PLoS One. 2018;13:e0199860. and two were evoked transient tests. 2525 Hrapcak S, Kuper H, Bartlett P, Devendra A, Makawa A, Kim M, et al. Hearing loss in HIV-infected children in Lilongwe, Malawi. PLoS One. 2016;11:e0161421., 2626 Christensen LA, Morehouse CR, Powell TW, Alchediak T, Silio M. Antiviral therapy in a child with pediatric human immunodeficiency virus (HIV): case study of audiologic findings. J Am Acad Audiol. 1998;9:292-8. Most studies that included acoustic immittance measurements performed them together with audiometry or ABR to confirm the type of hearing loss (Table 2).

Table 1
General characteristics of selected articles.
Table 2
Results of acoustic immittance measurements in the selected studies.

Most procedures (audiometry, ABR, and OAE) were performed similarly in several studies, although some authors lack methodological details. 55 Christopher N, Edward T, Sabrina BK, Agnes N. The prevalence of hearing impairment in the 6 months - 5 years HIV/AIDS-positive patients attending paediatric infectious disease clinic at Mulago Hospital. Int J Pediatr Otorhinolaryngol. 2013;77:262-5., 1515 Govender R, Eley B, Walker K, Petersen R, Wilmshurst JM. Neurologic and neurobehavioral sequelae in children with human immunodeficiency virus (HIV-1) infection. J Child Neurol. 2011;26:1355-64., 1616 Nakku D, Nyaiteera V, Llowet E, Nanseera D, Nakalema G, Westerberg B, et al. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in South Western Uganda. Int J Pediatr Otorhinolaryngol. 2017;101:172-7., 2020 Makar SK, Dhara S, Sinha AK, Chatterjee I, Dutta P. Nature and onset of communication disorder in pediatrics with HIV. Int J Ped Otorhinolaryngol. 2012;76:1065-6., 2424 Knox J, Arpadi SM, Kauchali S, Craib M, Kvalsvig JD, Taylor M, et al. Screening for developmental disabilities in HIV positive and HIV negative children in South Africa: results from the Asenze Study. PLoS One. 2018;13:e0199860. Some showed small differences, such as the tested frequencies or the thresholds that defined hearing loss. 44 Matas CG, Leite RA, Magliaro FC, Gonçalves IC. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS). Braz J Infect Dis. 2006;10:264-8., 2525 Hrapcak S, Kuper H, Bartlett P, Devendra A, Makawa A, Kim M, et al. Hearing loss in HIV-infected children in Lilongwe, Malawi. PLoS One. 2016;11:e0161421.

26 Christensen LA, Morehouse CR, Powell TW, Alchediak T, Silio M. Antiviral therapy in a child with pediatric human immunodeficiency virus (HIV): case study of audiologic findings. J Am Acad Audiol. 1998;9:292-8.
- 2727 Matas CG, Santos Filha VA, Juan KR, Pinto FR, Gonçalves IC. Manifestaçõesaudiológicasemcrianças e adultoscom AIDS. Pro Fono. 2010;22:269-74. For analysis purposes, the definition of hearing loss reported in each article was followed.

Physical examination: otoscopy

To provide more reliable information about the audiological results, 14 studies mentioned that they performed otoscopic evaluation (Table 3). However, some did not report details of this examination. 66 Matas CG, Iorio MC, Succi RC. Auditory disorders and acquisition of the ability to localize sound in children born to HIV-positive mothers. Braz J Infect Dis. 2008;12:10-4., 2222 Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51., 2323 Torre P, Cook A, Elliott H, Dawood G, Laughton B. Hearing assessment data in HIV-infected and uninfected children of Cape Town, South Africa. AIDS Care. 2015;27:1037-41., 2828 Buriti AK, Oliveira SHS, Muniz LF, Soares MJ. Evaluation of hearing health in children with HIV/AIDS. Audiol Commun Res. 2014;19:105-11. Hrapcack et al. 2525 Hrapcak S, Kuper H, Bartlett P, Devendra A, Makawa A, Kim M, et al. Hearing loss in HIV-infected children in Lilongwe, Malawi. PLoS One. 2016;11:e0161421. and Smith et al. 1818 Smith AF, Ianacone DC, Ensink RJ, Melaku A, Casselbrant ML, Isaacson G. Prevalence of hearing-loss among HAART-treated children in the Horn of Africa. Int J Pediatr Otorhinolaryngol. 2017;98:166e170. found more than one abnormal finding in the same child.

Table 3
Otoscopy findings.

Audiological findings

For the definition of hearing loss, the results of behavioral tests were not considered. HIV infection or AIDS were considered risk factors for hearing loss (OR = 5,364, p = 0.00) (Fig. 2). Eleven studies compared the findings of children with HIV/AIDS with control groups (HIV-negative, perinatally exposed but not infected, or unknown status for HIV). In these, there was a higher rate of hearing loss among children with HIV/AIDS when compared to the control groups (RR = 2,135, 95% CI = 1,733-2,631, p = 0.00; Fig. 3).

Fig. 2
Odds ratio for hearing loss in children with HIV/AIDS. Information from articles that did not report the number of children affected was excluded.

Fig. 3
Relative risk for hearing loss in children with HIV compared to control groups.

Mixed hearing loss was the type of loss less frequently found in children with HIV/AIDS, and no statistical difference was found between conductive and sensorineural loss (p = 0.119) between the studies.

Influence of age and gender

No study reported a statistically significant influence of gender on hearing loss in children with HIV/AIDS. Some studies have shown that older children with HIV/AIDS tend to have higher hearing loss rates, 44 Matas CG, Leite RA, Magliaro FC, Gonçalves IC. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS). Braz J Infect Dis. 2006;10:264-8., 55 Christopher N, Edward T, Sabrina BK, Agnes N. The prevalence of hearing impairment in the 6 months - 5 years HIV/AIDS-positive patients attending paediatric infectious disease clinic at Mulago Hospital. Int J Pediatr Otorhinolaryngol. 2013;77:262-5., 1414 Torre P, Yao TJ, Zeldow B, Williams P, Hoffman HJ, Siberry GK. Distortion product otoacoustic emission data in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents in the pediatric HIV/AIDS cohort study. Pediatr Infect Dis J. 2015;34:276-8., 1717 Chidziva C, Matsekete J, Bandason T, Shamu S, Dzongodza T, Matinhira N. Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe. Cent Afr J Med. 2015;61:56-61. but only Nakku et al. 1616 Nakku D, Nyaiteera V, Llowet E, Nanseera D, Nakalema G, Westerberg B, et al. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in South Western Uganda. Int J Pediatr Otorhinolaryngol. 2017;101:172-7. and Buriti et al. 2828 Buriti AK, Oliveira SHS, Muniz LF, Soares MJ. Evaluation of hearing health in children with HIV/AIDS. Audiol Commun Res. 2014;19:105-11. showed a statistically significant difference.

Hearing loss, CD4+ T lymphocyte count, and viral load count

Different ways of assessing HIV infection status were identified in different studies (Centers for Disease Control [CDC] classification, presence of opportunistic infections, clinical history, duration of HIV infection, and laboratory findings such as CD4+ T lymphocyte count and viral load, with different cut-off values for these). Consequently, due to the lack of standardization of these classifications, it was not possible to perform the meta-analysis.

Palacios et al. 1919 Palacios GC, Montalvo MS, Fraire MI, Leon E, Alvarez MT, Solorzano F. Audiologic and vestibular findings in a sample of human immunodeficiency virus type-1-infected Mexican children under highly active antiretroviral therapy. Int J Pediatr Otorhinolaryngol. 2008;72:1671-81. concluded that patients with hearing loss had earlier manifestations of HIV-related symptoms, higher viral load, and lower absolute values of CD4+ T-cell counts at the time of hearing evaluation and also at the time of ART start. A viral load greater than 400 copies/mL was associated to abnormalities in the distortion product OAE test. 1414 Torre P, Yao TJ, Zeldow B, Williams P, Hoffman HJ, Siberry GK. Distortion product otoacoustic emission data in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents in the pediatric HIV/AIDS cohort study. Pediatr Infect Dis J. 2015;34:276-8. The association between hearing impairment and duration of HIV infection was also emphasized by Buriti et al. 2828 Buriti AK, Oliveira SHS, Muniz LF, Soares MJ. Evaluation of hearing health in children with HIV/AIDS. Audiol Commun Res. 2014;19:105-11. and Makar et al. 2020 Makar SK, Dhara S, Sinha AK, Chatterjee I, Dutta P. Nature and onset of communication disorder in pediatrics with HIV. Int J Ped Otorhinolaryngol. 2012;76:1065-6.

Buritiet al. 2929 Buriti AK, Oliveira SH, Muniz LF. Hearing loss in children with HIV/AIDS. CoDAS. 2013;25:513-20. did not find a correlation between audiological findings and viral load. Since all patients evaluated in the study by Torre et al. 2323 Torre P, Cook A, Elliott H, Dawood G, Laughton B. Hearing assessment data in HIV-infected and uninfected children of Cape Town, South Africa. AIDS Care. 2015;27:1037-41. had viral load values below the detection limit, this parameter was not discussed.

On the other hand, Chao et al. 22 Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65. suggested that CD4+ T lymphocyte counts below 500 cells/mm3 would be risk factors for hearing loss in children with HIV (OR = 3.53; p = 0.02). Chidziva et al. 1717 Chidziva C, Matsekete J, Bandason T, Shamu S, Dzongodza T, Matinhira N. Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe. Cent Afr J Med. 2015;61:56-61. reported that the reference value for this risk would be a count below 350 cells/mm3 (OR = 2.1; p < 0.037). Also, Torre et al. 3030 Torre P, Zeldow B, Hoffman HJ, Buchanan A, Siberry GK, Rice M, et al. Hearing loss in perinatally human immunodeficiency virus-infected and human immunodeficiency virus-exposed but uninfected children and adolescents. Pediatr Infect Dis J. 2012;31:835-41. demonstrated an indeterminate association between hearing loss and CD4+T-cell count below 20%.

Effects of antiretroviral therapy

Nine studies did not provide any information on ART use among the studied children and five others reported that the evaluated children were using ART,but did not describe the adopted regimens. 1515 Govender R, Eley B, Walker K, Petersen R, Wilmshurst JM. Neurologic and neurobehavioral sequelae in children with human immunodeficiency virus (HIV-1) infection. J Child Neurol. 2011;26:1355-64., 3030 Torre P, Zeldow B, Hoffman HJ, Buchanan A, Siberry GK, Rice M, et al. Hearing loss in perinatally human immunodeficiency virus-infected and human immunodeficiency virus-exposed but uninfected children and adolescents. Pediatr Infect Dis J. 2012;31:835-41.

31 Bastos FN, Fleig R, Nascimento IB. Hearing abilities and analysis in an oralized hearing-impaired child with HIV: a case study. Rev CEFAC. 2010;12:700-8.

32 Romero AC, Alfaya LM, Gonçalves AS, Frizzo AC, Isaac ML. Auditory alterations in children infected by human immunodeficiency virus verified through auditory processing test. Int Arch Otorhinolaryngol. 2017;21:86-91.
- 3333 Taipale A, Pelkonen T, Taipale M, Roine I, Bernardino L, Peltola H, et al. Otorhinolaryngological findings and hearing in HIV-positive and HIV-negative children in a developing country. Eur Arch Otorhinolaryngol. 2011;268:1527-32.

Some treatment regimens reported in other studies were based on nucleoside/non-nucleoside reverse transcriptase inhibitors. Protease inhibitors were mentioned, 22 Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65., 88 Olusanya BO, Neumann KJ, Saunders JE. The global burden of disabling hearing impairment: a call to action. Bull World Health Organ. 2014;92:367-73., 2323 Torre P, Cook A, Elliott H, Dawood G, Laughton B. Hearing assessment data in HIV-infected and uninfected children of Cape Town, South Africa. AIDS Care. 2015;27:1037-41., 2929 Buriti AK, Oliveira SH, Muniz LF. Hearing loss in children with HIV/AIDS. CoDAS. 2013;25:513-20., 3434 Martins RH, Batista L, Souza AC, Costa GA, Zuliani A, OlbrichNeto J. Otolaryngologicmanifestations in children with AIDS. Braz J Otorhinolaryngol. 2001;67:204-11. as well as immunoglobulins. 3434 Martins RH, Batista L, Souza AC, Costa GA, Zuliani A, OlbrichNeto J. Otolaryngologicmanifestations in children with AIDS. Braz J Otorhinolaryngol. 2001;67:204-11. Only two studies reported dual-drug regimens. 2626 Christensen LA, Morehouse CR, Powell TW, Alchediak T, Silio M. Antiviral therapy in a child with pediatric human immunodeficiency virus (HIV): case study of audiologic findings. J Am Acad Audiol. 1998;9:292-8., 3434 Martins RH, Batista L, Souza AC, Costa GA, Zuliani A, OlbrichNeto J. Otolaryngologicmanifestations in children with AIDS. Braz J Otorhinolaryngol. 2001;67:204-11. Hearing loss was not correlated with ART use or its different treatment regimens 2222 Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51., 2525 Hrapcak S, Kuper H, Bartlett P, Devendra A, Makawa A, Kim M, et al. Hearing loss in HIV-infected children in Lilongwe, Malawi. PLoS One. 2016;11:e0161421. but the findings were conflicting in the literature. 22 Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65., 2929 Buriti AK, Oliveira SH, Muniz LF. Hearing loss in children with HIV/AIDS. CoDAS. 2013;25:513-20. ART duration was significantly associated with hearing loss in three studies. 1616 Nakku D, Nyaiteera V, Llowet E, Nanseera D, Nakalema G, Westerberg B, et al. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in South Western Uganda. Int J Pediatr Otorhinolaryngol. 2017;101:172-7., 1717 Chidziva C, Matsekete J, Bandason T, Shamu S, Dzongodza T, Matinhira N. Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe. Cent Afr J Med. 2015;61:56-61., 2828 Buriti AK, Oliveira SHS, Muniz LF, Soares MJ. Evaluation of hearing health in children with HIV/AIDS. Audiol Commun Res. 2014;19:105-11.

Due to the heterogeneity of these data, no meta-analysis could be performed regarding the effects of ART on the hearing status of children with HIV in the literature.

Discussion

It was observed that HIV and AIDS can influence the hearing health of children, according to this meta-analysis carried out without temporal limitation. No differentiation was made between the influence of HIV infection or AIDS, separately, because the assessed studies did not perform it either. The inclusion criteria adopted by most studies were only age and a positive test result for the virus.

After the neonatal hearing screening, the authors did not observe, among the selected studies, a standardization of hearing assessment in the children regarding the type of exam used or the moment at which they should be performed. In some of these studies, the same subject underwent different examinations, with different findings, turning harder the analysis. 1919 Palacios GC, Montalvo MS, Fraire MI, Leon E, Alvarez MT, Solorzano F. Audiologic and vestibular findings in a sample of human immunodeficiency virus type-1-infected Mexican children under highly active antiretroviral therapy. Int J Pediatr Otorhinolaryngol. 2008;72:1671-81., 2020 Makar SK, Dhara S, Sinha AK, Chatterjee I, Dutta P. Nature and onset of communication disorder in pediatrics with HIV. Int J Ped Otorhinolaryngol. 2012;76:1065-6., 2222 Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51., 2626 Christensen LA, Morehouse CR, Powell TW, Alchediak T, Silio M. Antiviral therapy in a child with pediatric human immunodeficiency virus (HIV): case study of audiologic findings. J Am Acad Audiol. 1998;9:292-8., 3333 Taipale A, Pelkonen T, Taipale M, Roine I, Bernardino L, Peltola H, et al. Otorhinolaryngological findings and hearing in HIV-positive and HIV-negative children in a developing country. Eur Arch Otorhinolaryngol. 2011;268:1527-32. It was not possible to make comparisons even when the same exam was used, because the studies used different methodologies, 2323 Torre P, Cook A, Elliott H, Dawood G, Laughton B. Hearing assessment data in HIV-infected and uninfected children of Cape Town, South Africa. AIDS Care. 2015;27:1037-41., 2525 Hrapcak S, Kuper H, Bartlett P, Devendra A, Makawa A, Kim M, et al. Hearing loss in HIV-infected children in Lilongwe, Malawi. PLoS One. 2016;11:e0161421., 2727 Matas CG, Santos Filha VA, Juan KR, Pinto FR, Gonçalves IC. Manifestaçõesaudiológicasemcrianças e adultoscom AIDS. Pro Fono. 2010;22:269-74. as previously highlighted in the review article by Ensink et al. 3535 Ensink RJ, Kuper H. Is hearing impairment associated with HIV? A systematic review of data from low- and middle-income countries. Trop Med Int Health. 2017;22:1493-504.

Even the hearing loss classification was not standardized between studies. The ABR results were considered to classify hearing losses as conductive, sensorineural, or mixed, but also as central or peripheral hearing loss. 44 Matas CG, Leite RA, Magliaro FC, Gonçalves IC. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS). Braz J Infect Dis. 2006;10:264-8. Peripheral hearing loss can be considered an impairment of the outer ear, middle ear, and even the cochlea, but this definition was not clear.

Also, four studies considered the number of ears instead of the number of affected children 2828 Buriti AK, Oliveira SHS, Muniz LF, Soares MJ. Evaluation of hearing health in children with HIV/AIDS. Audiol Commun Res. 2014;19:105-11.

29 Buriti AK, Oliveira SH, Muniz LF. Hearing loss in children with HIV/AIDS. CoDAS. 2013;25:513-20.
- 3030 Torre P, Zeldow B, Hoffman HJ, Buchanan A, Siberry GK, Rice M, et al. Hearing loss in perinatally human immunodeficiency virus-infected and human immunodeficiency virus-exposed but uninfected children and adolescents. Pediatr Infect Dis J. 2012;31:835-41., 3232 Romero AC, Alfaya LM, Gonçalves AS, Frizzo AC, Isaac ML. Auditory alterations in children infected by human immunodeficiency virus verified through auditory processing test. Int Arch Otorhinolaryngol. 2017;21:86-91. and were excluded in some meta-analyses. It seems more appropriate to consider the number of affected children, since the involvement of one or both ears does not necessarily reflect the severity of HIV infection in human hearing. However, it is possible that the same child may present different types of hearing loss in either ear. 3636 Rezende CE, Rodrigues RE, Haddad L, Yoshimura R, Rapoport PB. Manifestaçõesotológicasemcriançacomsíndrome da imunodeficiênciaadquirida. Braz J Otorhinolaryngol. 2004;70:430-4.

The collaboration of children and their parents or caregivers could limit the reliability of the findings between the exams, especially the subjective ones, but no study has discussed this possible bias. The most reliable exam in this regard would be the ABR, but it is a more difficult exam to perform because of its longer duration, higher cost, and sometimes the need for the child's sedation.

Another criticism is that the presence of cerumen in the external ear canal, acute otitis media, and even fungal otitis externa were considered as causes of hearing loss in some studies, instead of being treated before the hearing evaluation, which clearly influenced the obtained result.

Little is known about the effects of ART on the hearing health of children and adolescents with HIV. 3030 Torre P, Zeldow B, Hoffman HJ, Buchanan A, Siberry GK, Rice M, et al. Hearing loss in perinatally human immunodeficiency virus-infected and human immunodeficiency virus-exposed but uninfected children and adolescents. Pediatr Infect Dis J. 2012;31:835-41., 3737 Laughton B, Cornell M, Boivin M, VanRie A. Neurodevelopment in perinatally HIV-infected children: a concern for adolescence. J Int AIDS Soc. 2013;16:18603. As shown, different drug regimens, time of use, age at onset, and even incomplete information led to inconsistent findings. 22 Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65., 2222 Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51., 2727 Matas CG, Santos Filha VA, Juan KR, Pinto FR, Gonçalves IC. Manifestaçõesaudiológicasemcrianças e adultoscom AIDS. Pro Fono. 2010;22:269-74. Some researchers have pointed out that some drugs may cause mitochondrial DNA damage. 11 Matas CG, Angrisani RG, Magliaro FC, Segurado AA. Audiological manifestations in HIV-positive adults. Clinics (Sao Paulo). 2014;69:469-75., 3838 Williams PL, Seage GR, Van Dyke RB, Siberry GK, Griner R, Tassiopoulos K, et al. A trigger-based design for evaluating the safety of in uteroantiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers. Am J Epidemiol. 2012;175:950-61. The ototoxic effects of some medications commonly administered to patients with HIV (such as antibiotics) may also be considered confounding factors. 1616 Nakku D, Nyaiteera V, Llowet E, Nanseera D, Nakalema G, Westerberg B, et al. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in South Western Uganda. Int J Pediatr Otorhinolaryngol. 2017;101:172-7., 3333 Taipale A, Pelkonen T, Taipale M, Roine I, Bernardino L, Peltola H, et al. Otorhinolaryngological findings and hearing in HIV-positive and HIV-negative children in a developing country. Eur Arch Otorhinolaryngol. 2011;268:1527-32., 3434 Martins RH, Batista L, Souza AC, Costa GA, Zuliani A, OlbrichNeto J. Otolaryngologicmanifestations in children with AIDS. Braz J Otorhinolaryngol. 2001;67:204-11. No selected studies have evaluated hearing thresholds at higher frequencies, which are most commonly compromised in cases of ototoxicity. 1111 Assuiti LF, Lanzoni GM, Santos FC, Erdmann AL, Meirelles BH. Hearing loss in people with HIV/AIDS and associated factors: an integrative review. Braz J Otorhinolaryngol. 2013;79:248-55.

Few studies have evaluated the correlation between the laboratory status of HIV infection (mainly viral load and CD4+ T lymphocyte count) and hearing loss. Once again, conflicting findings in the literature were observed, especially related to the different cut-offs for CD4+ T lymphocytes. In turn, it should be noted that all studies used cross-sectional measures, which may not reflect the actual status of HIV infection, especially regarding viral load. Furthermore, some treatment regimens were started immediately after birth, and viral replication itself may not reached levels high enough to lead to direct damage. 2222 Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51.

Conclusion

Hearing loss in childhood can lead to important language, social, educational, and psychological limitations. It is known that HIV is a risk factor for hearing loss, but the literature shows conflicting findings in this association. Also, there is no standardization regarding the best hearing tests to be employed or the age of onset for evaluation after the neonatal hearing screening.

Further studies are needed to explain the effects of HIV/AIDS on children's hearing, as well as its management. It is suggested that prospective studies be performed using the same audiological exams in all phases, with greater methodological detail. Therefore, the evolution of human hearing in people with HIV could be observed longitudinally. This knowledge may contribute to preventive measures for childhood hearing loss.

As HIV/AIDS affects children worldwide, it is also suggested that protocols for periodic auditory assessment of these children after neonatal screening be developed. Early diagnosis leads to timely rehabilitation, aiming to prevent the limitations caused by hearing loss.

  • Please cite this article as: Bentivi JO, Azevedo CM, Lopes MK, Rocha SC, Silva PC, Costa VM, et al. Audiological assessment of children with HIV/AIDS: a meta-analysis. J Pediatr (Rio J). 2020;96:537-45.
  • ☆☆
    Study conducted at Federal University of Maranhão, São Luís, MA, Brazil.

Acknowledgments

The authors would like to give special thanks to Professors Monica Gama and Vanda Simões for their contributions to this work.

The authors are grateful for the support of Fundação de Amparo à Pesquisa e Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA).

References

  • 1
    Matas CG, Angrisani RG, Magliaro FC, Segurado AA. Audiological manifestations in HIV-positive adults. Clinics (Sao Paulo). 2014;69:469-75.
  • 2
    Chao CK, Czechowicz JA, Messner AH, Alarcón J, Kolevic RL, Rodriguez MM, et al. High prevalence of hearing impairment in HIV-infected Peruvian children. Otolaryngol Head Neck Surg. 2012;146:259-65.
  • 3
    Sanjar FA, Queiroz BE, Miziara ID. Otolaryngologic manifestations in HIV disease - clinical aspects and treatment. Braz J Otorhinolaryngol. 2011;77:391-400.
  • 4
    Matas CG, Leite RA, Magliaro FC, Gonçalves IC. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS). Braz J Infect Dis. 2006;10:264-8.
  • 5
    Christopher N, Edward T, Sabrina BK, Agnes N. The prevalence of hearing impairment in the 6 months - 5 years HIV/AIDS-positive patients attending paediatric infectious disease clinic at Mulago Hospital. Int J Pediatr Otorhinolaryngol. 2013;77:262-5.
  • 6
    Matas CG, Iorio MC, Succi RC. Auditory disorders and acquisition of the ability to localize sound in children born to HIV-positive mothers. Braz J Infect Dis. 2008;12:10-4.
  • 7
    Lewis DR, Marone SA, Mendes BC. Multiprofessional committee on auditory healthy: COMUSA. Braz J Otorhinolaryngol. 2010;76:121-8.
  • 8
    Olusanya BO, Neumann KJ, Saunders JE. The global burden of disabling hearing impairment: a call to action. Bull World Health Organ. 2014;92:367-73.
  • 9
    Olusanya BO, Solanke OA. Maternal and neonatal factors associated with mode of delivery under a universal newborn hearing screeningprogramme in Lagos, Nigeria. BMC Pregnancy Childbirth. 2009;9:41.
  • 10
    Kallail KJ, Downs DW, Scherz JW. Communication disorders in individuals with HIV/AIDS. Kansas J Med. 2008;1:62-9.
  • 11
    Assuiti LF, Lanzoni GM, Santos FC, Erdmann AL, Meirelles BH. Hearing loss in people with HIV/AIDS and associated factors: an integrative review. Braz J Otorhinolaryngol. 2013;79:248-55.
  • 12
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000098.
  • 13
    Wong WC, Cheung CS, Hart GJ. Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours. Emerg Themes Epidemiol. 2008;5:23.
  • 14
    Torre P, Yao TJ, Zeldow B, Williams P, Hoffman HJ, Siberry GK. Distortion product otoacoustic emission data in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents in the pediatric HIV/AIDS cohort study. Pediatr Infect Dis J. 2015;34:276-8.
  • 15
    Govender R, Eley B, Walker K, Petersen R, Wilmshurst JM. Neurologic and neurobehavioral sequelae in children with human immunodeficiency virus (HIV-1) infection. J Child Neurol. 2011;26:1355-64.
  • 16
    Nakku D, Nyaiteera V, Llowet E, Nanseera D, Nakalema G, Westerberg B, et al. HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in South Western Uganda. Int J Pediatr Otorhinolaryngol. 2017;101:172-7.
  • 17
    Chidziva C, Matsekete J, Bandason T, Shamu S, Dzongodza T, Matinhira N. Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe. Cent Afr J Med. 2015;61:56-61.
  • 18
    Smith AF, Ianacone DC, Ensink RJ, Melaku A, Casselbrant ML, Isaacson G. Prevalence of hearing-loss among HAART-treated children in the Horn of Africa. Int J Pediatr Otorhinolaryngol. 2017;98:166e170.
  • 19
    Palacios GC, Montalvo MS, Fraire MI, Leon E, Alvarez MT, Solorzano F. Audiologic and vestibular findings in a sample of human immunodeficiency virus type-1-infected Mexican children under highly active antiretroviral therapy. Int J Pediatr Otorhinolaryngol. 2008;72:1671-81.
  • 20
    Makar SK, Dhara S, Sinha AK, Chatterjee I, Dutta P. Nature and onset of communication disorder in pediatrics with HIV. Int J Ped Otorhinolaryngol. 2012;76:1065-6.
  • 21
    Matas CG, Sansone AP, Iorio MC, Succi RC. Avaliação Audiológica emcrianças nascidas de mãessoropositivas para o vírus da imunodeficiênciahumana. Braz J Otorhinolaryngol. 2000;66:317-24.
  • 22
    Maro II, Fellows AM, Clavier OH, Gui J, Rieke CC, Wilbur JC, et al. Auditory impairments in HIV-infected children. Ear Hear. 2016;37:443-51.
  • 23
    Torre P, Cook A, Elliott H, Dawood G, Laughton B. Hearing assessment data in HIV-infected and uninfected children of Cape Town, South Africa. AIDS Care. 2015;27:1037-41.
  • 24
    Knox J, Arpadi SM, Kauchali S, Craib M, Kvalsvig JD, Taylor M, et al. Screening for developmental disabilities in HIV positive and HIV negative children in South Africa: results from the Asenze Study. PLoS One. 2018;13:e0199860.
  • 25
    Hrapcak S, Kuper H, Bartlett P, Devendra A, Makawa A, Kim M, et al. Hearing loss in HIV-infected children in Lilongwe, Malawi. PLoS One. 2016;11:e0161421.
  • 26
    Christensen LA, Morehouse CR, Powell TW, Alchediak T, Silio M. Antiviral therapy in a child with pediatric human immunodeficiency virus (HIV): case study of audiologic findings. J Am Acad Audiol. 1998;9:292-8.
  • 27
    Matas CG, Santos Filha VA, Juan KR, Pinto FR, Gonçalves IC. Manifestaçõesaudiológicasemcrianças e adultoscom AIDS. Pro Fono. 2010;22:269-74.
  • 28
    Buriti AK, Oliveira SHS, Muniz LF, Soares MJ. Evaluation of hearing health in children with HIV/AIDS. Audiol Commun Res. 2014;19:105-11.
  • 29
    Buriti AK, Oliveira SH, Muniz LF. Hearing loss in children with HIV/AIDS. CoDAS. 2013;25:513-20.
  • 30
    Torre P, Zeldow B, Hoffman HJ, Buchanan A, Siberry GK, Rice M, et al. Hearing loss in perinatally human immunodeficiency virus-infected and human immunodeficiency virus-exposed but uninfected children and adolescents. Pediatr Infect Dis J. 2012;31:835-41.
  • 31
    Bastos FN, Fleig R, Nascimento IB. Hearing abilities and analysis in an oralized hearing-impaired child with HIV: a case study. Rev CEFAC. 2010;12:700-8.
  • 32
    Romero AC, Alfaya LM, Gonçalves AS, Frizzo AC, Isaac ML. Auditory alterations in children infected by human immunodeficiency virus verified through auditory processing test. Int Arch Otorhinolaryngol. 2017;21:86-91.
  • 33
    Taipale A, Pelkonen T, Taipale M, Roine I, Bernardino L, Peltola H, et al. Otorhinolaryngological findings and hearing in HIV-positive and HIV-negative children in a developing country. Eur Arch Otorhinolaryngol. 2011;268:1527-32.
  • 34
    Martins RH, Batista L, Souza AC, Costa GA, Zuliani A, OlbrichNeto J. Otolaryngologicmanifestations in children with AIDS. Braz J Otorhinolaryngol. 2001;67:204-11.
  • 35
    Ensink RJ, Kuper H. Is hearing impairment associated with HIV? A systematic review of data from low- and middle-income countries. Trop Med Int Health. 2017;22:1493-504.
  • 36
    Rezende CE, Rodrigues RE, Haddad L, Yoshimura R, Rapoport PB. Manifestaçõesotológicasemcriançacomsíndrome da imunodeficiênciaadquirida. Braz J Otorhinolaryngol. 2004;70:430-4.
  • 37
    Laughton B, Cornell M, Boivin M, VanRie A. Neurodevelopment in perinatally HIV-infected children: a concern for adolescence. J Int AIDS Soc. 2013;16:18603.
  • 38
    Williams PL, Seage GR, Van Dyke RB, Siberry GK, Griner R, Tassiopoulos K, et al. A trigger-based design for evaluating the safety of in uteroantiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers. Am J Epidemiol. 2012;175:950-61.

Publication Dates

  • Publication in this collection
    11 Nov 2020
  • Date of issue
    Sep-Oct 2020

History

  • Received
    17 Nov 2019
  • Accepted
    20 Nov 2019
  • Published
    3 Jan 2020
Sociedade Brasileira de Pediatria Av. Carlos Gomes, 328 cj. 304, 90480-000 Porto Alegre RS Brazil, Tel.: +55 51 3328-9520 - Porto Alegre - RS - Brazil
E-mail: jped@jped.com.br