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The physical sequelae of perinatally acquired HIV in adolescents: a research proposal



As the global access of antiretrovirals for HIV-infected infants improves, so the body of perinatally HIV-infected adolescents (PHIVA) grows. The neurological and physical complications of HIV, both in children and in adults, are well established, however there is a paucity of data pertaining to PHIVA, a group of people who have had a lifetime exposure to the virus and to antiretrovirals. There has been a resounding call for further research in this area, as well as for the development of policies and programmes for this population. The aim of this study is to determine the physical sequelae in PHIVA and to propose a model of care for this population.


Through interviews with PHIVA, the perceived physical challenges will be established. Thereafter a cohort study with age-matched participants will determine if PHIVA have any limitations in fatigue, endurance, motor function and muscle strength, body mass index, peripheral neuropathy, level of disability and quality of life. Using these results, a model of care will be proposed through the nominal group technique with both PHIVA and clinicians working in HIV and adolescence.


Current data shows that AIDS-related deaths have declined by 48% from 2005 to 2016 [1], however the human immunodeficiency virus (HIV) remains the second leading cause of death in adolescence globally [2] and the leading cause in Africa [3]. The global scale-up of antiretroviral therapy (ART) in the management of HIV has shifted the paediatric HIV pandemic to chronic disease management, with a growing body of perinatally HIV-infected adolescents (PHIVA) [4]. In 2016 there were an estimated 2.1 million adolescents aged 10–19 years living with HIV, with 84% living in sub-Saharan Africa [3] and although perinatal HIV transmission forms the majority of infection route, the specific number of PHIVA is unknown [4].

While the paediatric brain has strong neural plasticity, it also has a degree of neural vulnerability where adverse environmental factors can impact on normal development [5, 6]. One of these adverse factors can be the HI virus, which is able to cross the blood brain barrier and infiltrate the central nervous system causing neurocognitive impairment [7]. Even with the early use of ART many children with HIV still present with neurodevelopmental problems due to neuroinflammation, vascular dysfunction and hypercoagulability [8]. In addition to damage done to the developing nervous system by the HI virus, the long term use of ART needs to be considered. Hepatotoxicity, mitochondrial toxicity, skin toxicity, hypersensitivity and lipodystrophy are some well-known adverse effects of ART [9, 10]. Depending on the class of drug and the individual, a variety of neurotoxic adverse effects exist from ART, including mania, psychosis, insomnia, irritability, vivid dreams [11].

Some of the established challenges that children and adults with HIV face are peripheral neuropathy, fatigue, decreased endurance and muscle strength, motor function impairments and body mass index changes [12,13,14,15,16,17,18,19,20,21]. Concerning these challenges, there is little data available on what PHIVA face.

With the advent of ART and its increased availability to perinatally infected HIV positive children, there is a growing number of adolescents living with HIV and ART use since birth, facing a lifetime of chronic illness management [22,23,24,25], the consequences of which are still being established [4]. Overall, there is a lack of data available for the challenges that PHIVA face [26]. Of the studies that have been done on neurodevelopment in PHIVA, the majority are from resource-rich countries, and not from resource-scarce countries (where PHIVA are more likely to face running a child-headed household; have poorer access to health care; face poverty, deprivation and opportunistic infections [26]), where there is the highest prevalence of PHIVA [26].

The literature has identified a clear need for further research to be done in the area of neurodevelopment in PHIVA (especially in resource-scarce countries), as well as for the urgent development of policies and programmes to cater for PHIVA [26,27,28]. Although models of care for different areas of managing HIV are available [29,30,31,32] to date there is no literature presented on suggested models of care for PHIVA. Furthermore, since the challenges that PHIVA face is a relatively new area of concern, any existing models of care may well not be sufficiently responsive to this population, as is often the case with existing models of care based on historical information [33].

The aim of this study is, over three phases, to determine what the perceived challenges are that PHIVA face due to physical sequelae of HIV; to then establish these challenges clinically; and lastly to propose a model of care for PHIVA. This manuscript will provide the outline of the research proposal used to meet the study’s intentions.

Main text

The study is designed as a mixed methods study over three phases. In the first phase qualitative information will be gathered through semi-structured individual interviews. The second phase is designed as a cohort study with a comparison group of age-matched participants. In the third phase, a model of care for PHIVA will be proposed and consensus will be obtained through the nominal group technique.

Subject selection

Adolescence is defined as ages 10–19 years [2, 34], with early (10–15 years), middle (14–17 years) and late (16–19 years) stages [35]. For the purposes of this study, early and middle phases of 10–14 years and 15–17 years respectively will be used (late phase adolescents will not be included due to the age limitations of the outcome measures). Participants will be recruited from an existing cohort of PHIVA involved in a clinical trial looking at the chronic effects of growing up with HIV: the childhood HAART alterations in normal growth, genes and aGing evaluation study (CHANGES) (M120871). To date CHANGES has approximately 255 PHIVA (aged 10 and above) attending a clinic every 6 months, as well as a data base of HIV negative adolescents, providing the ideal source of participants for this study. The CHANGES trial is based at Rahima Moosa Mother and Child Hospital (RMMCH), Johannesburg, South Africa. Data routinely collected for CHANGES includes (but is not limited to) the participant’s body mass index, quality of life scores, clinical data (such as viral load, CD4 count etcetera).

This study has been approved by the Human Research Ethics Committee of the University of the Witwatersrand (certificate number M180226), and registered with the South African National Health Research Database (reference GP_201806_010). Written, informed consent, assent and permission will be obtained from the necessary parties.

Sample size and inclusion/exclusion criteria

For the first phase, data will be collected for participants in two groups, namely early adolescence and middle adolescence. This will continue until data saturation is reached in each age group. Initially eight participants per age group (i.e. 16 participants) will be invited to participate and booked for interviews. Adolescents aged 10–17 years will be invited to take part in the study, but will be excluded if they have physical and/or cognitive impairments rendering them unable to participate in the interview process or if they have impairments not related to HIV (e.g. traumatic brain injury).

For phase two, the inclusion and exclusion criteria remain the same, but in addition, age-matched HIV negative participants will be invited to participate as the age-matched, comparison cohort. To date, CHANGES has an age appropriate population of 255 HIV positive participants. These adolescents are representative of the community of PHIVA. A sample of 154 HIV positive participants would give a confidence level of 95% (5% margin of error). A further 154 HIV negative participants would comprise the age-matched, comparison cohort, thus a total of 308 adolescents would be required for phase two of this study. (Sample size was calculated using Raosoft, Inc© [36]).

Based on the findings of phase one and two, phase three will involve the development of a model of care for PHIVA. This will be put forward for consensus using the nominal group technique (NGT) to two populations, namely a group of PHIVA (sourced from CHANGES), and a group of clinical experts in the field of HIV and adolescents. During phase one and two the principal investigator (PI) will take note of the clinical experts encountered at RMMCH. Snow-ball sampling will also be used to source participants as the clinical experts, who would need to have worked with adolescents with HIV as a nurse, medical doctor, physiotherapist or occupational therapist. It is recommended that five to nine people are used per group for NGT [37].

Study procedures

Phase one

Adolescents and their parent/guardian will be approached and invited to participate in phase one on the day that they are attending the clinic. Through semi-structured interviews participants will meet with the PI individually to explore what the participant perceives as challenges due to the physical sequelae of HIV and how this impacts on their activity and participation levels. The interviewer will use open-ended questions to explore what the participant enjoys doing socially; what they find physically difficult; what they feel that they are not able to do that their friends can do; what their attitude is towards their health etcetera.

The interviews will be audio-recorded and transcribed verbatim at a later stage. The PI will take field notes during the interview and at the end of each interview the PI will capture the essence of the interview session [38].

Phase two

Participants and their guardians will be invited to take part in phase two of the study on the day that they attend the clinic. After they complete their doctor’s appointment, they will meet with the researcher and data will be collected from the participants as per Table 1.

Table 1 Data collection parameters for phase two

Phase three

Data gathered in phase one and two will inform phase three: the development of a model of care for PHIVA. The model of care will be put forward for consensus via the NGT. Two groups of five to nine participants [37] will be used: one of PHIVA and one of clinical experts (as described in the inclusion criteria). The participants and PI will meet on an allocated date and the NGT structure will follow the method as described in the literature, namely, to give an explanation of the purpose and procedure; allow for the silent generation of ideas; participants then share ideas; a group discussion; followed by voting and ranking to prioritise the ideas [37].

The application of the international classification of functioning, disability and health (ICF) as a conceptual framework for disability has been described in the literature and is used as a common language in discussing disability [39]. Based on this, this study will utilise the ICF as its conceptual framework (as shown in Fig. 1). The impairments, activity limitations and participation restrictions identified in phase one and two will feed into the development of the model of care for phase three.

Fig. 1
figure 1

Conceptual framework for the physical sequelae of perinatally acquired HIV in adolescents [39]

Data analysis

The data from the interviews will be organised, coded and analysed by the PI and another coder. Substantive statements will be identified in the transcribed interviews and thematic analysis will be undertaken using the general inductive approach to analyse the data [40], with manifest analysis being used to quantify the content [41]. Thereafter the coders will discuss the material and identify the themes, categories and sub-categories [41]. This improves the validity through triangulation [41]. The field notes taken during the data collection will be an added aspect of triangulation.

Data collected in phase two will be transferred to Microsoft Excel™ 2016 where frequencies, means and standard deviations will be calculated for descriptive statistical analysis. Statistica™ will be used to analyse the data further. The authors hypothesise that the age-matched, comparison cohort will acquire better scores. P values of < 0.05 will be considered statistically significant. T tests will compare clinical data, demographic data and data from the outcome measures. Mean composite scores will be compared between the PHIVA and age-matched, comparison cohort. To measure the variable difference between the two groups the Chi squared test and Kruskal–Wallis one-way ANOVA will be used. A logistic regression will be used to analyse factors associated with disability.

For phase three, due to the nature of the ranking, NGT yields both quantitative and qualitative data [42]. The qualitative data will be analysed inductively (as per phase one) and the ranking of items will be analysed as quantitative data using descriptive statistics with frequencies and means.

Table 2 gives a summary of the methodology for the study across the three phases.

Table 2 Summary of the methodology for the study across three phases


Establishing the perceived and actual physical sequelae of perinatally transmitted HIV in adolescents will address one of the gaps in knowledge that we have as clinicians working with PHIVA. Creating a model of care will assist health care providers in early identification, assessment and management of potential physical problems, including the necessary referral of the PHIVA to relevant members of the interdisciplinary team. By addressing the challenges, one hopes to improve the quality of life and community participation of PHIVA. Informing this research with the voice of the affected population in the assessment and development of the model of care ensures that we are working for adolescents, with adolescents, and thus potentially optimising the uptake of the model of care.


Although the study site has a large feeder area, taking participants from only one site results in a somewhat homogeneous population and thus may not produce results generalizable to the global population. However, this study will provide the starting point for determining the physical sequelae in PHIVA and the basis of a model of care for this population, which could be tested in further research.

Furthermore, the HIV related fatigue scale has not yet been used in adolescents, nor tested across all cultures, however, it remains one of the few tools that are available for the use of establishing fatigue in HIV [43].



antiretroviral therapy


childhood HAART alterations in normal growth, genes and aGing evaluation study


human immunodeficiency virus


international classification of functioning, disability and health

Movement ABC-2:

movement assessment battery for children—second edition


nominal group technique

PedsQL™ 4.0:

pediatric quality of life inventory version 4.0


perinatally HIV-infected adolescents


principal investigator


quality of life


Rahima Moosa Mother and Child Hospital


World Health Organisation disability assessment schedule for children


  1. UNAIDS data 2017. Accessed 20 Oct 2017.

  2. World Health Organization. Health for the world’s adolescents: a second chance in the second decade. 2014. Accessed 20 Oct 2017.

  3. UNICEF data 2017. Turning the tide against AIDS will require more concentrated focus on adolescents and young people. 2017. Accessed 20 Oct 2017.

  4. Sohn AH, Hazra R. The changing epidemiology of the global paediatric HIV epidemic: keeping track of perinatally HIV-infected adolescents. J Int AIDS Soc. 2013;16:18555.

    Article  Google Scholar 

  5. Weiss B. Vulnerability of children and the developing brain to neurotoxic hazards. Environ Health Perspect. 2000;108(Supplement 3):375–81.

    PubMed  PubMed Central  Google Scholar 

  6. Dobbing J. Vulnerable periods in developing brain. In: Dobbing J, editor. Brain, behaviour, and iron in the infant diet. London: Springer; 1990. p. 1–17.

    Chapter  Google Scholar 

  7. Strazza M, Pirrone V, Wigdahl B, Nonnemacher MR. Breaking down the barrier: the effects of HIV-1 on the blood–brain barrier. Brain Res. 2011;1399:96–115.

    Article  CAS  Google Scholar 

  8. Blokhuis C, Kootstra N, Caan M, Pajkrt D. Neurodevelopmental delay in pediatric HIV/AIDS: current perspectives. Neurobehav HIV Med. 2016;7:1–13.

    Google Scholar 

  9. Shubber Z, Calmy A, Andrieux-Meyer I, Vitoria M, Renaud-Théry F, Shaffer N, et al. Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis. AIDS. 2013;27:1403–12.

    Article  CAS  Google Scholar 

  10. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet. 2000;356:1423–30.

    Article  CAS  Google Scholar 

  11. Abers MS, Shandera WX, Kass JS. Neurological and psychiatric adverse effects of antiretroviral drugs. CNS Drugs. 2014;28:131–45.

    Article  CAS  Google Scholar 

  12. Arenas-Pinto A, Thompson J, Musoro G, Musana H, Lugemwa A, Kambugu A, et al. Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial. J Neurovirol. 2016;22:104–13.

    Article  CAS  Google Scholar 

  13. Pardo CA, McArthur JC, Griffin JW. HIV neuropathy: insights in the pathology of HIV peripheral nerve disease. J Peripher Nerv Syst. 2001;6:21–7.

    Article  CAS  Google Scholar 

  14. Jong E, Oudhoff LA, Epskamp C, Wagener MN, van Duijn M, Fischer S, et al. Predictors and treatment strategies of HIV-related fatigue in the combined antiretroviral therapy era. AIDS. 2010;24:1387–405.

    Article  CAS  Google Scholar 

  15. Chisati E, Vasseljen O. Aerobic endurance in HIV-positive young adults and HIV-negative controls in Malawi. Malawi Med J. 2015;27:5.

    Article  CAS  Google Scholar 

  16. Walker A-J. Preliminary investigation into the exercise endurance of HIV infected school going children aged seven to ten years. 2015. Accessed 20 Oct 2017.

  17. Keyser RE, Peralta L, Cade WT, Miller S, Anixt J. Functional aerobic impairment in adolescents seropositive for HIV: a quasiexperimental analysis. Arch Phys Med Rehabil. 2000;81:1479–84.

    Article  CAS  Google Scholar 

  18. Grinspoon S, Mulligan K. Weight loss and wasting in patients infected with human immunodeficiency virus. Clin Infect Dis. 2003;36(Suppl 2):S69–78.

    Article  Google Scholar 

  19. Khondowe O, Nikodem V, Frantz J, Harper K. A systematic review on the effect of HIV infection on motor and cognitive development of infants and toddlers. Afr J Phys Health Educ Recreat Dance. 2015;21(1.2):240–52.

    Google Scholar 

  20. Arbeitman LE, O’Brien RC, Somarriba G, Messiah SE, Neri D, Scott GB, et al. Body mass index and waist circumference of HIV-infected youth in a Miami cohort: comparison to local and national cohorts. J Pediatr Gastroenterol Nutr. 2014;59:449–54.

    Article  Google Scholar 

  21. Macdonald H, Nettlefold L, Maan E, Côté H, Alimenti A. Muscle power in children, youth and young adults who acquired HIV perinatally. J Musculoskelet Neuronal Interact. 2017;17:27–37.

    CAS  PubMed Central  Google Scholar 

  22. Idele P, Gillespie A, Porth T, Mahy M, Kasedde S, Luo C. Epidemiology of HIV and AIDS among adolescents: current status, inequities, and data gaps. J Acquir Immune Defic Syndr. 2014;66(Supplement 2):S144–53.

    Article  Google Scholar 

  23. Smith R, Wilkins M. Perinatally acquired HIV infection: long-term neuropsychological consequences and challenges ahead. Child Neuropsychol. 2015;21:234–68.

    Article  Google Scholar 

  24. Brady MT, Oleske JM, Williams PL, Elgie C, Mofenson LM, Dankner WM, et al. Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era. JAIDS. 2010;53:86–94.

    PubMed  Google Scholar 

  25. Hazra R, Siberry GK, Mofenson LM. Growing up with HIV: children, adolescents, and young adults with perinatally acquired HIV infection. Annu Rev Med. 2010;61:169–85.

    Article  CAS  Google Scholar 

  26. Laughton B, Cornell M, Boivin M, Van Rie A. Neurodevelopment in perinatally HIV-infected children: a concern for adolescence. J Int AIDS Soc. 2013;16:18603.

    Article  Google Scholar 

  27. Lowenthal ED, Bakeera-Kitaka S, Marukutira T, Chapman J, Goldrath K, Ferrand RA. Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges. Lancet Infect Dis. 2014;14:627–39.

    Article  Google Scholar 

  28. Smith R, Chernoff M, Williams PL, Malee KM, Sirois PA, Kammerer B, et al. Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence. Pediatr Infect Dis J. 2012;31:592–8.

    Article  Google Scholar 

  29. Smith LR, Fisher JD, Cunningham CO, Amico KR. Understanding the behavioral determinants of retention in HIV care: a qualitative evaluation of a situated information, motivation, behavioral skills model of care initiation and maintenance. AIDS Patient Care STDs. 2012;26:344–55.

    Article  Google Scholar 

  30. Teasdale CA, Besser MJ. Enhancing PMTCT programmes through psychosocial support and empowerment of women: the mothers2mothers model of care. S Afr J HIV Med. 2008;9:60–4.

    Google Scholar 

  31. Bradford JB, Coleman S, Cunningham W. HIV system navigation: an emerging model to improve HIV care access. AIDS Patient Care STDs. 2007;21:S49–58.

    Article  Google Scholar 

  32. Ford N, Reuter H, Bedelu M, Schneider H, Reuter H. Sustainability of long-term treatment in a rural district: the Lusikisiki model of decentralised HIV/AIDS care. S Afr J HIV Med. 2006;25:17–22.

    Article  Google Scholar 

  33. Davidson P, Halcomb E, Hickman L, Phillips J, Graham B. Beyond the rhetoric: what do we mean by a model of care? Aust J Adv Nurs. 2006;23:47–55.

    PubMed  Google Scholar 

  34. UNICEF, 2016. Adolescents living with HIV: developing and strengthening care and support services, Geneva: UNICEF Regional Office for Central and Eastern Europe and the Commonwealth of Independent States (CEECIS). 2016. Accessed 20 Oct 2017.

  35. World Health Organization. WHO 2010 participants manual: IMAI one-day or orientation on adolescents living with HIV. 2010. Accessed 20 Oct 2017.

  36. Sample size calculator.

  37. Potter M, Gordon S, Hamer P. The nominal group technique: a useful consensus methodology in physiotherapy research. N Z J Physiother. 2004;32:126–30.

    Google Scholar 

  38. Gill P, Stewart K, Treasure E, Chadwick B. Methods of data collection in qualitative research: interviews and focus groups. Br Dent J. 2008;204:291–5.

    Article  CAS  Google Scholar 

  39. Kostanjsek N. Use of the international classification of functioning, disability and health (ICF) as a conceptual framework and common language for disability statistics and health information systems. BMC Public Health. 2011;11(Suppl 4):S3.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Thomas DR. A general inductive approach for analyzing qualitative evaluation data. Am J Eval. 2006;27:237–46.

    Article  Google Scholar 

  41. Bengtsson M. How to plan and perform a qualitative study using content analysis. NursingPlus Open. 2016;2:8–14.

    Article  Google Scholar 

  42. Dobbie A, Rhodes M, Tysinger JW, Freeman J. Using a modified nominal group technique as a curriculum evaluation tool. Fam Med. 2004;36:402–6.

    PubMed  Google Scholar 

  43. Potterton J. HIV and fatigue—is there a role for physiotherapists? Phys Ther Rev. 2016;21:236–40.

    Article  Google Scholar 

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Authors’ contributions

NCW, JP and VN were involved in the conception and design of the study. NCW drafted the manuscript. JP and VN reviewed the manuscript. All authors read and approved the final manuscript.


We wish to acknowledge the CHANGES team for allowing access to the study site and providing the authors with the patient numbers required for the sample size calculations.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

Not applicable. This article is a research proposal and no datasets were generated or analysed.

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Not applicable.

Ethics approval and consent to participate

This study has been approved by the Human Research Ethics Committee of the University of the Witwatersrand (Certificate Number M180226), and registered with the South African National Health Research Database (reference GP_201806_010). Written, informed consent, assent and permission will be obtained from the necessary parties.


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Correspondence to Nicolette Comley-White.

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Comley-White, N., Potterton, J. & Ntsiea, V. The physical sequelae of perinatally acquired HIV in adolescents: a research proposal. BMC Res Notes 12, 62 (2019).

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