|Year : 2020 | Volume
| Issue : 1 | Page : 8
Craniofacial morphology of HIV-infected adolescents undergoing highly active antiretroviral therapy (HAART): An original research
M Neeraja1, Anand Garabadu2, Subash Chandra Nayak2, Monalisa Das2, Debashish Dash2, Anurag Tiwari2, Abhishek Singh Nayyar3
1 Department of Dentistry, Great Eastern Medical School and Hospital, Srikakulam, Andhra Pradesh, India
2 Department of Orthodontics and Dentofacial Orthopedics, HiTech Dental College and Hospital, Bhubaneswar, India
3 Department of Oral Medicine and Radiology, Saraswati Dhanwantari Dental College and Hospital and Post-graduate Research Institute, Parbhani, Maharashtra, India
|Date of Submission||23-Feb-2020|
|Date of Decision||30-Mar-2020|
|Date of Acceptance||15-May-2020|
|Date of Web Publication||15-Jul-2020|
Dr. Abhishek Singh Nayyar
44, Behind Singla Nursing Home, New Friends' Colony, Model Town, Panipat - 132 103, Haryana
Source of Support: None, Conflict of Interest: None
OBJECTIVES: To analyze the craniofacial morphology in child patients and adolescents by evaluating the skeletal cephalometric profile of the HIV infected patients in this age group and comparing them with the HIV-negative controls.
MATERIALS AND METHODS: The present study was a planned case-control study which included 25 HIV-positive adolescent patients aged between 10 and 18 years (the study group) who were compared with 25 age- and sex-matched HIV-negative adolescent controls (the control group). All the patients had been HIV infected via a vertical transmission with positive serology confirmed in two different tests and had been kept on HAART since they were born. The diagnostic aids used for orthodontic documentation included facial photographs, digital orthopantomographs, lateral teleradiographs, and study models.
RESULTS: With reference to the methodologies used for taking the cephalometric values, all the methods used were in strong agreement with each other for almost all the variables studied and had high intra-class correlation coefficient values except Co-A, SN.ANSPNS, and SNB which, too, had a good agreement of 60%. Nevertheless, the agreement was positive for these variables, too, since the P values obtained were found to be statistically significant (P < 0.05).
CONCLUSION: Most of the measurements in the HIV-infected adolescents were found to be similar to the ones obtained for the HIV-negative controls, although, the study results highlighted the significance of further studies to be conducted in this regard, especially, the longitudinal study designs wherein the said variables can be studied on a follow-up basis in longitudinal studies to have an idea of the exact changes observed and their pattern in the included groups.
Keywords: Craniofacial morphology, highly active antiretroviral therapy, HIV-positive adolescents
|How to cite this article:|
Neeraja M, Garabadu A, Nayak SC, Das M, Dash D, Tiwari A, Nayyar AS. Craniofacial morphology of HIV-infected adolescents undergoing highly active antiretroviral therapy (HAART): An original research. J Orthodont Sci 2020;9:8
|How to cite this URL:|
Neeraja M, Garabadu A, Nayak SC, Das M, Dash D, Tiwari A, Nayyar AS. Craniofacial morphology of HIV-infected adolescents undergoing highly active antiretroviral therapy (HAART): An original research. J Orthodont Sci [serial online] 2020 [cited 2020 Sep 19];9:8. Available from: http://www.jorthodsci.org/text.asp?2020/9/1/8/289831
| Introduction|| |
With the advent of the highly active antiretroviral therapy (HAART) in the 1990s, patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) have undergone an increase in the quality and assumption of their life.,, The adverse effects of the combination of these antiretroviral drugs started to be identified through compromised physiologic functions in various systems and organs much later. The changes identified in the pediatric group included mitochondrial toxicity, hepatic and renal toxicity, insulin resistance, hypertension, cardiac dysfunction with an increased risk for cardiovascular diseases, and decreased bone mineral density.,,,,,,,,,,,,,,,
Dental considerations in patients with HIV/AIDS have concentrated more on the prevalence, diagnosis, and treatment of the varied oral presentations seen due to immunocompromise.,,, Furthermore, such changes have been recognized not only in the teeth and their associated structures but also in the craniofacial growth pattern seen in the HIV-infected/AIDS patients in the younger age groups who are undergoing HAART., Several studies and various authors have illustrated a plethora of chronic systemic diseases leading to changes in the craniofacial growth and development,,,,,,,, however, there has been a relative dearth of such studies on the HIV-infected/AIDS patients. Also, there is no way to estimate whether disease or its treatment does have an impact on craniofacial growth and development.
Recently, studies have pointed out that there are fewer studies about children and adolescents with HIV and most importantly, about the adverse effects of HAART on this age group of the population. In agreement with most of the recent concerns raised in this particular area of research, the present study was planned to analyze the craniofacial morphology in child patients and adolescents by evaluating the skeletal cephalometric profile of the HIV-infected patients in this age group wherein HIV was transmitted via vertical transmission, and hence, submitted to HAART and comparing them with the HIV-negative controls.
| Materials and Methods|| |
Study design, source of data, and selection criteria used in the study
The present study was a planned case-control study which included adolescent patients seropositive for HIV and the HIV-negative controls who attended the outpatient department for orthodontic treatment for 1 year. The protocol of the study was approved by the university research ethics committee. Twenty-five HIV-positive adolescent patients aged between 10 and 18 years (study group) were selected and then, compared with 25 age- and sex-matched HIV-negative adolescent controls (control group). All the patients had been HIV infected via a vertical transmission with positive serology confirmed in two different tests and had been kept on HAART since they were born. The patients were, also, categorized into three age ranges (10–12, 13–15, and 16–18 years). The patients who were undergoing any long-term systemic therapy for severe chronic diseases (except AIDS in the study group) and who had received radio-chemotherapy or, any previous orthodontic and orthopedic treatment in the past were excluded from the study.
Protocol of the study
The diagnostic aids used for orthodontic documentation included facial photographs, digital orthopantomographs, lateral teleradiographs, and study models. For the present study, teleradiographs were used, and over them, various cephalometric points of the hard profile were identified and used for evaluating the craniofacial morphology. Cephalometric tracings of 18 (linear and angular) measurements on teleradiographs were done. The mean values of each measurement were, then, compared between the two groups based on their specific age range. Overall, 14 points and 18 (linear and angular) measurements were used for the assessment of the craniofacial growth pattern, all based on the previous studies conducted by various authors in the past. To decrease the possibility of errors, cephalometric points, and measurements were traced with two different methods. In the initial (semi-automated) method, a dental radiologist used a Compaq Presario microcomputer (Specifications: 1.7 GHz, 768 Mb RAM, HD 30 GB, Windows XP SP3; Pentium 4; Hewlett Packard, Palo Alto, Ca) and Radiocef Studio Software (RadioMemory, Belo Horizonte). The cephalometric landmarks were marked manually while the software traced the said lines and angles including the relevant measurements. In the second (manual) method, for each radiograph, an orthodontist used a transparent acetate sheet (Specifications: Ultraphan; 3M Unitek, Monrovia, Calif) measuring 8-3-10 inches in dimensions and 0.003 inches in thickness with a propelling pencil with 0.5-mm thick graphite to mark the required points. All the measurements were listed into a spreadsheet (Specifications: Microsoft Office Excel 2007; Microsoft, Redmond, Wash) to get the mean values of each angle and linear measurement calculated by the semiautomated and manual methodologies. The data obtained for the study and control groups were, then, compared. It was hypothesized that pubertal growth spurt in girls occurred from 10 years of age reaching its maximum at 12 years of age whereas, in boys, it started from 9 years and reached its peak at 14 years of age. Hence, the time interval between 9 and 12 years was chosen as the main growth spurt period for both the sexes combinedly. Two other age ranges were, also, defined viz. before the growth spurt in the 6–8 years period and after growth spurt during the 13–17 years period.
Statistical analysis used
The data were analyzed by using the Epiinfo software while the Bartlett test was performed to verify the homogeneity of the variances (P = 0.05). For variables without a normal distribution, the Wilcoxon test was applied while to determine the reliability of the agreement between two measurement methodologies, an intra-class correlation coefficient test was used for the conduct of statistical analysis. The significance level was put at 0.05 or 5%. P < 0.05 was considered statistically significant.
| Results|| |
Twenty-five subjects were evaluated in the study group of which 10 were girls and 15 were boys, all aged between 10 and 18 years of age with a mean age of 14 years. All the study participants had been diagnosed with HIV since birth and were being treated with HAART from the first year of their lives. During clinical evaluation, a mean CD41 T lymphocytes count of 752 cells per cubic millimeter (minimum, 180 cells/mm3 and maximum, 1727 cells/mm3) was observed in the study group. Two patients had no detected viral load while the said patients were, also, the ones to have CD41 T lymphocyte counts within the normal range (273 and 180 cells/mm3). Four of the patients used first-line drugs composed of two nucleoside reverse transcriptase inhibitors and 1 non-nucleoside reverse transcriptase inhibitor. Twelve patients used second-line combinations including 2 NRTIs with one protease inhibitor (PI) with ritonavir boosters. Two patients used two NRTIs plus one PI. Three patients used the following combinations as 2 NRTIs and 1 PI along with ritonavir boosters plus 1 PI; and 2 NRTIs with 1 PI and 1 integrase inhibitor; 3 NRTIs and 1 PI with ritonavir boosters in the 3rd patient.
With reference to the methodologies used for taking the cephalometric values, all the methods used were in strong agreement with each other for almost all the variables studied [Table 1] and had high intra-class correlation coefficient values [Table 2] except Co-A, SN.ANSPNS, and SNB which, too, had a good agreement of 60%. Nevertheless, the agreement was positive for these variables, too, since the P values obtained were found to be statistically significant (P < 0.05). The cephalometric measurements of the study and control groups were compared according to the age ranges included as 10–12 years, 13–15 years, and 16–18 years of age [Table 3], [Table 4], [Table 5].
|Table 2: Intra-class correlation coefficient analysis showing a comparison between the two methods of cephalometric measurements|
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|Table 3: Comparison of cephalometric measurements of the study and control groups in the 10-12 years age groups|
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|Table 4: Comparison of cephalometric measurements of the study and control groups in the 13-15-year age groups|
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|Table 5: Comparison of cephalometric measurements of the study and control groups in the 16-18 year age groups|
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In the 10–12-year age group, when considering the mean values, positions of the maxilla, and mandible in the study group were found to be retruded in relation to the skull base when compared with the control group. Also, the growth pattern in the study group was seen as more horizontal with the effective size of the bone bases increased than as seen for the control group. Despite the same, though, the difference observed was not found to be statistically significant except for the palatal plane inclination as is seen in [Table 3]. With regard to the mean values in the 13–15-year age group, the maxilla was retruded slightly while the mandible was found to be protruded in the study group in relation to the base of the skull than as compared with the control group. Also, the former had a decreased effective size of the maxillary bone with an increased effective size of the mandible than the latter group.
Furthermore, in the 13–15-year age group, growth patterns were almost similar in both the study and the control groups. None of the variables related to the maxillary and mandibular positions in an anteroposterior direction, growth pattern, and effective linear measurements in this particular age group showed statistically significant differences between the study and control groups [Table 4].
With regards to the mean values in the 16–18-year age group, the position of the maxilla in the study group was, again, retruded while the mandible protruded in relation to the skull base than seen in the control group. Also, although, the former had an effective maxillary size smaller than that seen in the latter group, the effective mandibular size was similar between the two groups. Furthermore, the growth pattern was more horizontal in the study group than in the control group, though, the only statistically significant difference found was in the position of the maxilla in the anteroposterior direction (SNA) [Table 5].
| Discussion|| |
Adolescents seropositive for HIV, now, attend the dental hospitals and demand full treatment for their oral health conditions.,, Studies evaluating growth and development of face have identified that up to 5 years of age, craniometric dimensions get established along with the maxillofacial skeleton and a significant increase in the height and width of the jaws is, also, observed.,,,,,,, However, the greatest gain in growth occurs only after 6 years of age with a continuous increase in jaw length and facial height, width, and depth observed until the craniofacial dimensions reach maturity and become more or, less stable during the adolescence between 13 and 15 years of age., Because of the drawbacks inherent in a cross-sectional study, differences that could be found in different age groups in the present study suggested continuous craniofacial growth changes with the whole face growing vertically and horizontally in both the groups.
The results of the present study revealed that two of the measurements had statistically significant differences viz. the angle between the palatal plane and base of the skull (SN.ANSPNS) and the angle demonstrating the position of the maxilla in anteroposterior direction in relation to the base of the skull (SNA). Furthermore, in the 10–12 years of age range, the SN.ANSPNS values showed a rotation of the maxilla (palatal plane) which was increased in the HIV-positive patients as against the HIV-negative age- and sex-matched controls wherein these values were seen to diminish. Also, angle SNA was shown to significantly decrease in the 13–15 and 16–18 years age groups wherein the reduction in measurements was interpreted as retrusion of the maxillary bone in accordance with the study conducted previously.
Furthermore, although, the present study was not longitudinal, 3 interpretations could be perceived for this type of craniofacial change observed in the study group in the present study with reference from the previously conducted studies. The first and the most significant interpretation amongst them was that this type of change seen in the study group was a consequence of the respiratory pattern seen in the HIV positive adolescents which gets compromised in this group of patients due to recurrent airway infections.,,,,,,,,, Also, SNA may, also, decrease in patients with compromised respiratory function of upper airway due to habits such as mouth-breathing.,
HIV infection being associated or not associated with varying states of immune activation and inflammatory processes can, also, affect the process osteoclastogenesis increasing rate of apoptosis of primary osteoblasts, decreasing calcium deposition and alkaline phosphatase activity, diminishing specific bone proteins, and compromising the differentiation of the mesenchymal cells into active bone-forming osteoblasts.,,,, The long-term use of HAART might, also, be responsible for the systemic changes that affect the growth of these seropositive individuals.,
HAART emerged as a solution to deleterious effects caused by the virus by lowering the circulating viral load. The immunologic reconstitution induced by the use of HAART, expressed by an increase in CD4 T lymphocytes, allows these patients to be clinically stable with reductions in the incidence of opportunistic infections that, further, compromise the nutritional status of these group of individuals and bring malnutrition. Although gains in height and weight among the HIV patients on HAART are vital and calculable, these gains are relatively less marked than the respective gains seen in the HIV-negative controls.
The results of the present study were not supportive of changes in the other linear and angular values included which were found to be statistically insignificant when compared with the control group, however, it was possible to identify a trend toward a decrease in the linear measurements of the maxilla and mandible along with the base of the skull in the study patients, especially, in the age groups of 13–15 and 16–18 years. In the present study, among the said variables in the mentioned age groups, 14 angular and linear measurements were found to be lower than those seen in the HIV-negative controls. This type of difference could, also, be observed in five of the measurements in the 10–12-year age group as against in seven of the measurements in the 13–15-year age group.
| Conclusion|| |
The results of the present study highlighted the significance of further studies to be conducted in this regard, especially, the longitudinal study designs wherein the said variables can be studied on a follow-up basis in longitudinal studies to have an idea of the exact changes observed and their pattern in the included groups. The differences, though, in the majority of the measurements made in the HIV infected and control groups in the present study were not found to be significant enough to generate a statistically significant difference in the craniofacial growth pattern studied. Although 18 comparisons were studied in the included study and control groups in the present study, only two of the measurements had statistically significant differences with marginally significant P values. Since no overall differences could be observed between the two groups in the present study, it could be hypothesized that the beneficial effects of HAART overcome the associated adverse effects of the said therapy.
Limitations of the present study
Nevertheless, the present study was based on cross-sectional study design and could not establish a cause and effect relationship which can be considered as the major limitation of the present study. Another limitation and confounding factor in the present study was that only teleradiographs of adolescents who were referred for orthodontic treatment were included in the present study and consequently, they had some amount of deviation from normality in both the groups included. On the contrary, an ideal study design would include all adolescents in the said age groups irrespective of their need for orthodontic treatment. Also, ethical concerns can be raised and are a major constraint due to exposure of young adolescents to ionizing radiation not only during the growth periods but, also, at various times throughout their lives only to check for the possible changes in their craniofacial growth pattern. Furthermore, it is difficult to correctly predict whether such changes are seen as a result of the active disease process and the reactive immune activation and inflammatory processes seen due to HIV infection or, due to HAART since most of the HIV infected patients who are under medical treatment are already under HAART.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]