|Year : 2018 | Volume
| Issue : 3 | Page : 289-296
Oral health of children and adolescents infected with human immunodeficiency virus and impact of highly active antiretroviral therapy on quality of life
Ravleen Nagi1, Deepa J Patil2, Shashikant Sahu3
1 Department of Oral Medicine and Radiology, New Horizon Dental College and Research Institute, Bilaspur, Chhattisgarh, India
2 Department of Oral Medicine and Radiology, Manu Bhai Patel Dental College, Vadodara, Gujarat, India
3 Department of General and Plastic Surgery, Burn Trauma Research Centre, Bilaspur, Chhattisgarh, India
|Date of Submission||14-Jul-2017|
|Date of Acceptance||06-Mar-2018|
|Date of Web Publication||18-Oct-2018|
Dr. Ravleen Nagi
Department of Oral Medicine and Radiology, New Horizon Dental College and Research Institute, Bilaspur, Chhattisgarh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Human immunodeficiency virus (HIV) is global pandemic disease with progression of HIV infection to acquired immunodeficiency syndrome (AIDS) varying considerably among individuals, it is faster and more severe in children, due to the immaturity of the immune system. It may lead to various oral manifestations thus compromising nutrition and oral health of patients. Due to increasing frequency of pediatric HIV infection, all dental health-care providers should familiarize themselves with the early diagnosis of pathological conditions of the oral cavity and recommend management strategies for the treatment of such children. With the introduction of successful highly active antiretroviral therapy (HAART), oral health-care providers are now more likely to encounter children and adolescents who live longer with HIV/AIDS. This review would discuss the role of oral health-care provider in management of HIV infection especially in children and adolescents and would also highlight the effect of HAART on the quality of life on pediatric patients.
Keywords: Adolescents, acquired immunodeficiency syndrome, children, human immunodefi ciency virus infection, oral health
|How to cite this article:|
Nagi R, Patil DJ, Sahu S. Oral health of children and adolescents infected with human immunodeficiency virus and impact of highly active antiretroviral therapy on quality of life. J Indian Acad Oral Med Radiol 2018;30:289-96
|How to cite this URL:|
Nagi R, Patil DJ, Sahu S. Oral health of children and adolescents infected with human immunodeficiency virus and impact of highly active antiretroviral therapy on quality of life. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 Mar 24];30:289-96. Available from: http://www.jiaomr.in/text.asp?2018/30/3/289/243660
| Introduction|| |
Oral health care is an important component of the management of patients with human immunodeficiency virus (HIV) infection. A poorly functioning dentition can adversely affect the quality of life, complicate the management of medical conditions, and create or exacerbate nutritional and psychosocial problems. HIV is a global pandemic disease. As of 2015, approximately 36.7 million people were living with HIV globally. There were almost 1.1 million deaths from AIDS in 2015 down from 2 million in 2005. It is estimated that 55,000–60,000 children were born every year to mothers who are HIV positive. These newborns whose mothers did not take any treatment have an estimated 30% chance of becoming infected during the mother's pregnancy, labor, or through breastfeeding after 6 months., In India, the main mode of HIV transmission in children is through the vertical route, including transplacentally, during pregnancy, during delivery, or postnatally during breastfeeding. Although a cure is not in sight, highly active antiretroviral therapy (HAART) has made HIV/AIDS a chronic, manageable disease, and early identification of HIV infection can result in timely access to health care for the child and supportive therapy for the family or caregiver.,
| Oral Manifestations of Human Immunodeficiency Virus|| |
Oral manifestations are often among the first symptoms in HIV-infected patients and have been associated with immune suppression., Moreover, oral candidiasis and oral hairy leukoplakia are predictors of AIDS evolution and are related with CD4 T-lymphocyte cell count <200 cells/ml., The prevalence of oral manifestations in HIV-infected adults tends to vary from country to country. Previous studies, at least in Africa, showed a wide range of prevalence rates from 1.5% up to 94%. However, in HIV-infected children, the prevalence of oral manifestations in developed countries has been reported to be as high as 72%., Oral lesions seen in HIV pediatric patients are illustrated in [Table 1].
|Table 1: EC-Clearinghouse and the World Health Organization classification of oral manifestations of pediatric HIV disease (1993)|
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| Oral Candidiasis|| |
The most common soft-tissue lesion in children with HIV infection is pseudomembranous oral candidiasis/oral thrush (reported in approximately 75% of cases). Erythematous candidiasis and angular cheilitis are also commonly observed in children with HIV infection. A number of factors may influence the risk for candidiasis in children. Feeding behaviors and nutritional requirements that increase the frequency of fermentable carbohydrates intake (e.g., formula, juices, milk, dietary supplements), especially when delivered with bottles, support the growth of candidiasis.
Oral rinsing, nutritional and medication management, and cleansing the entire mucosal and gingival tissue area beginning at birth may help to control oral candida and delay the progression of oral candidiasis. Oral hygiene instructions should be given to both children and the caregivers, and to young children, the caregiver's role in the oral hygiene process should be stressed. Residue of food and medicine on the oral tissues (mucosa, gingiva) and on the teeth should be removed by the caregivers of young children and independently by older children through rinsing with water or mechanical cleansing. [Table 2] shows topical and systemic antifungal medications for pediatric populations with oral candidiasis.
|Table 2: Topical and systemic antifungal medications for pediatric populations with oral candidiasis|
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| Angular Cheilitis|| |
Angular cheilitis appears as cracks or fissures at the commissures of the lips. As angular cheilitis may represent poor diet and poor feeding in addition to fungal infection, the oral health-care provider should assess the diet, oral habits, and/or HIV status of a child with angular cheilitis. Consultation should occur with the primary-care team regarding nutritional support and vitamin supplementation, which may improve this condition in children.
| Parotid Swelling|| |
Parotid swelling is the second most commonly reported oral lesion, with a prevalence of up to 30%. It is usually asymptomatic and bilateral and spontaneously resolves and recurs. The reason for the swelling is not well understood, and medication side effects have been offered as a possible explanation.
| Xerostomia|| |
Xerostomia has been observed in pediatric patients. The frequency is unknown, and the etiology is not clear. The administration of gamma globulin and antiretroviral drugs such as didanosine (ddI), lamivudine, and some protease inhibitors has been suggested as a possible cause for xerostomia in some children.,
Although increased caries have been observed in some children with HIV infection, the relationship between xerostomia and dental caries has not been demonstrated in clinical studies of children with HIV infection. Symptoms include dry stools, low urine volume, high fluid consumption, eating of “watery, loose” foods, and complaints of dry mouth. Sugarless gum and frequent consumption of water or highly diluted fruit juices should be used to alleviate xerostomia.
| Dental Caries|| |
The dental literature suggests that children with HIV infection are at greater risk for dental caries and gingivitis than children without HIV infection. The increased risk is due, in part, to baby-bottle tooth decay, progressive immunodeficiency, low CD4 counts, effects of medications on salivary flow and oral flora, developmental delay, and/or failure to thrive. Extrinsic factors such as diet, inadequate oral hygiene, socioeconomic status, lack of caregiver knowledge, and frequent use of the bottle while going to sleep may be additional risk factors.,, Even correlation between pediatric HIV infection and delayed tooth eruption have been reported in a study by Hauk MJ for which the exact cause is still unknown, but the malnutrition responsible for poor ill health of children may be an important cofactor.
Treatment should include remineralization of noncavitated, smooth-surface lesions, and restorative treatment of cavitated lesions. Establishment of recall intervals should be based on caries risk status, with high-risk patients being seen more frequently. Caries risk should be reassessed at each recall visit, and future care should be planned accordingly. In addition to fluoride varnishes, therapy in adolescents should include pit and fissure sealants and proper use of certain sugarless chewing gums that may provide protection.
| Gingival and Periodontal Disease|| |
HIV infection, changes in saliva, and xerostomia contribute to the severity of plaque-related diseases., The clinician should perform a comprehensive gingival and periodontal examination, which includes a periodontal probing depth record [Figure 1].
| Apthous Ulcers|| |
Patients with HIV infection often suffer from persistent, painful ulcers that commonly occur on the soft palate, buccal mucosa, tonsillar area, or tongue, which are referred to as aphthous ulcers. Aphthous ulcers in children with HIV (estimated prevalence, <10%) can present serious problems, such as pain and impaired ability to eat. In addition to prolonged course, size and location may be atypical. Topical corticosteroids should be used to manage aphthous ulcers.
| Linear Gingival Erythema|| |
Linear gingival erythema is a progressive disease described in HIV-positive patients and is considered to be an early stage of necrotizing periodontitis. It is most commonly associated with the upper and lower anterior dentition, has been observed in pediatric patients [Figure 2].
|Figure 2: Linear gingival erythema involving marginal gingival in relation to right mandibular anteriors|
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| Hyperpigmentation|| |
Some studies have demonstrated the oral melanin hyperpigmentation in HIV positive children and young adult, which may be due to use of antifungal or antiretroviral drugs or decreased CD4 T lymphocyte cell count may play a vital role in inducing pigmentation.
| Kaposi Sarcoma|| |
Kaposi sarcoma (KS) is a most common malignancy seen in HIV-infected adults after non-Hodgkin's lymphoma. It is rarely seen in children (2.5%) but most commonly observed in pediatric patients of Africa. Its cause has been correlated with progressive low CD4 count and immunosuppression. The color of lesions shows variations from red, purple to brown and appear as macular or nodular lesions. Dermal lesions could occur along with oral lesions where hard plate, soft palate, gingiva, and dorsum of tongue are most common sites. The treatment of lesions mainly consists of initiation of HAART therapy along with other treatment modalities such as surgical resection, radiation therapy, intralesional vincristine/vinblastine, sclerotherapy, and cryptherapy.,
| Role of Medical and Oral Health-Care Provider|| |
The provision of care should be coordinated between medical and oral health-care providers.,
Role of medical provider
The medical provider should encourage all patients under his/her care to schedule a semi-annual oral health examination and to adhere to the oral health care-provider's recommendations regarding appropriate follow-up. All medical health-care providers should be aware of oral health referral sources for patients under their care. Documentation that a dental referral was made or that the patient is under the care of a dental provider should be evident within the clinical care plan of the medical record. The medical provider should forward any requested clinical information to the patient's oral health-care provider in a timely fashion.,
Role of oral health-care provider
Oral health-care provider should be involved in the initial management and be a participant of the primary care team for patients. Understanding the psychosocial, medical, and family issues that could be associated with HIV illness, obtaining a detailed medical and social history of the child, performing an oral-facial-dental evaluation at each visit, and establishing an appropriate recall interval for assessment of the patient's oral health status are keys to the preventive strategy. Recall intervals should be based on each patient's caries history, plaque and debris index, and treatment adherence. To ensure adequate access to oral health-care services, structural, financial, personal, and cultural barriers should be considered and addressed by the oral health-care staff.
The oral health-care provider should make aware the patient about their oral health status and make parents aware to educate their children about the oral lesions of AIDS and how to prevent them. Counseling is required to break the news gently to child with help of counselor. Counselor should also prepare the child for anti retroviral therapy (ART). Clinicians should organize various health camps at community level and should also communicate to the patient's medical provider if any clinical findings that may signify a change in the patient's systemic health or any planned, extensive surgical procedures that may impact the patient's systemic health. Another focus of dentist should be on patient's nutritional status as HIV-infected children usually suffer from poor appetite, mouth sores, and diarrhea. Children with persistent diarrhea require 20–30% extra calories per day and zinc tablets 20 mg/day for 2 weeks are also prescribed. 1 RDA of micronutrient and vitamins are given if child's diet is not containing micronutrients. The mother should be educated about need for additional energy requirements, diet modifications, safe food preparation, hygiene issues, and other relevant precautionary measures with regular visit of 2–4 weeks of children to clinician.
Patients with HIV infection may develop associated skin manifestations and cervical lymphadenopathy; therefore, extraoral head and neck examinations and oral soft-tissue examinations should be performed at each visit. Findings should be discussed with the patient and the patient's primary care provider. As HIV-related medications may affect dental treatment and cause adverse effects, the patient's oral health-care provider should review all medications being used by the patient and should understand the potential for these medications to affect oral health care.
Dental treatment modifications for patients with HIV infection should be based on the patient's general medical status rather than his/her HIV infection. Dentists who become aware of a patient's risk for HIV infection or who identify a clinical condition that may be associated with HIV infection should refer the patient for HIV counseling and testing., Clinicians must know CD3 and CD4 T-lymphocyte amount and proportion; that patients with severe AIDS disease according to American Academy of Pediatrics Dentistry and World Health Organization classification, should be on antibiotic prophylaxis to prevent opportunistic infections; and to solicit supplementary laboratory examinations including hepatitis, herpes, varicella zoster, and papillomavirus with of purpose to offer secure management for HIV-infected children. In general dental practice, patients with an absolute neutrophil count below 1,500/mm3 and/ or with liver functions tests will need antibiotic prophylaxis. Patients with low platelet quantities may require extra hemostasis procedures or a platelet transfusion prior to surgical procedure. Panel on antiretroviral therapy and medical management of HIV-infected children recommended to initiate ART regimens in patients based on age, clinical status, and CD4 cell count. In Infants <12 months of age and children with advanced HIV disease, ART needs to be started urgently. In patients with increasing RNA levels, declining CD4 levels especially CDC stage 3 and development of clinical signs and symptoms of HIV initiate ART. [Table 3] depicts HIV infection stage based on CD4 cell count.
|Table 3: Human immunodeficiency virus infection stage based on CD4 cell count|
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| Antiretroviral Therapy in Pediatric Patients|| |
ART reduce the progression of HIV disease and improve the quality of life of HIV-infected children and young adults. The major goals of ART in children are restoring immune function as measured by CD4 cell count, minimizing viral replication, minimizing viral drug resistance strains, and reducing side effects to ART drugs. Maximizing adherence to ART in HIV-infected children and adolescents should be reinforced. Poor adherence leads to virologic resistance and treatment failure. Issues related to adherence should be discussed with child's parents and then therapy should be started. Triple drug therapy, that is, either a protease inhibitor, non-nucleoside reverse transcriptase inhibitor or nucleoside reverse transcriptase inhibitor is prescribed. The last classes of drug are attachment inhibitor, coreceptor inhibitors, and fusion inhibitors and they are usually used for treating HIV infection in treatment experienced patients. Fixed drug combinations are most commonly preferred as they reduce the cost of treatment and dose in pediatric patients that are given according to body surface area or body weight. Food and drug administration (FDA) approved ART drugs for pediatric patients that are shown in [Table 4]. Pediatric ART regimens are depicted in [Table 5]. Next question arises when to initiate antiretroviral therapy in children. Many trials have been conducted in symptomatic patients and in patients with low CD4T lymphocyte counts but Cohen et al. suggested that ART should be initiated in asymptomatic adults with CD4 count >500 cells/m3. Early therapy slows immune system destruction, and preserves immune function, prevents clinical disease progression with reduction of non-AIDS associated complications. It also reduces the drug resistance of virus particles and drug-induced side effects. [Table 6] depicts treatment recommendations for ART initiation in children and adolescents. ARV therapy especially with PIs and NNRIs-related side effects are vey less and it could be usually avoided by substituted by another ARV drug or by supportive therapy, which are shown in [Table 7]. In addition various ART drugs give rise to orofacial adverse reactions, which are summarized in [Table 8]. HIV lipodystrophy syndrome is common adverse reaction characterized by generalized loss of fat, especially at nasolabial folds and temples. If hypersensitivity reactions (skin rash) especially to abacavir drug was reported, discontinue the drug and do not restart the therapy regardless of HLA-B*5701 status.
|Table 4: Food and drug administrationapproved antiretroviral drugs for pediatric patients|
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|Table 6: Treatment recommendations for initiation of antiretroviral therapy in children and adolescents with HIV infection|
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|Table 7: Table showing substituting with alternative antiretroviral drug therapy in case of antiretroviral drug related toxicity in children and adolescents|
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In poor communities where ART is expensive, treatment should be planned accordingly. It should consist of treatment of infection, control of HIV progression, and finally restoration of esthetics. Some less expensive alternatives should be prescribed, for example, genitan violet and chlorhexidine were found to be as effective for treating oral candidiasis. Moreover, clinicians should regularly screen these patients for oral hygiene and xerostomia.
| Impact of Highly Active Antiretroviral Therapy on Quality of Life|| |
Quality of life (QoL) is an important parameter to evaluate the impact of HAART on the progression of AIDS. According to World Health Organization (WHO), concept of QoL is “an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.” Adherence to HAART controls the progression of disease and reduces mortality rates, thus improving the patients QoL. HAART regimens appear to have positive effects on CD4 count, HIV viral loads, and reduce body weight. Treatment of several psychological aspects such as pain, symptom distress, and depression has been reported in HIV patients receiving HAART therapy.,,
| Conclusion|| |
Oral health should be an integral part of primary health care for all patients with HIV/AIDS. It compromises nutrition due to oral manifestations and aching in the patients. The oral lesions were more frequently recorded in children not on HAART. Early identification of HIV infection can result in timely access to health care for the child and supportive therapy for the family or caregiver. Proper coordination between medical and dental health-care provider is needed to ensure regular screening for oral lesions and appropriate early management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
U.S. Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General—Executive Summary. Rockville, MD: U.S. Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health; 2000. Available from: http://www.nidr.nih.gov/sgr/execsumm.htm
. [Last updated on 2018 Jul].
Cohen MS, Hellmann N, Levy JA, DeCock K, Lange J. The spread, treatment, and prevention of HIV-1: Evolution of a global pandemic. J Clin Invest 2008;118:1244-54.
AIDS Epidemic Update 2008. UNAIDS/WHO. working group on global HIV / AIDS surveillance. Available from: http://www.unaids.org
. [Last accessed on 2008].
Manikandan S, Suresh Kumar V, Ramesh K. Oral manifestations of HIV infected children undergoing highly active antiretroviral therapy. J Pierre Fauchard Acad 2013;27:49-52.
Levi J. The public health challenges of the HIV epidemic. Am J Public Health 2000;90:1023-4.
Hogg RS, Rhone SA, Yip B, Sherlock C, Conway B, Schechter MT, et al
. Antiviral effect of double and triple drug combinations amongst HIV infected adults: Lessons from the implementation of viral load-driven antiretroviral therapy. AIDS 1998;12:279-84.
Ketchem L, Berkwitz RJ, Mcllveen L, Forrester D, Rakusan T. Oral findings in HIV-seropositive children. Peadiatr Dent 1990;12:143-6.
European Collaborative Study. Children born to women with HIV-1 infection: Natural history and risk and transmission. Lancet 1991;337:253-60.
Ramírez-Amador V, Esquivel-Pedraza L, Sierra-Madero J, Soto-Ramirez L, González-Ramírez I, Anaya-Saavedra G, et al
. Oral clinical markers and viral load in a prospective cohort of Mexican HIV-infected patients. AIDS 2001;15:1910-1.
Rwenyonyi CM, Kutesa A, Muwazi L, Okullo I, Kasangaki A, Kekitinwa A. Oral Manifestations in HIV/AIDS Infected Children. Eur J Dent 2011;5:291-8.
Ramos-Gomez FJ, Folayan MO. Oral Health Considerations in HIV infected children. Curr HIV/AIDS Rep 2013;10:283-93.
Scully C, el-Kabir M, Samaranayake LP. Candida and oral candidosis: A review. Crit Rev Oral Biol Med 1994;5:125-57.
Powderly WG, Mayor KH, Perfect GR. Diagnosis and treatment of oropharyngeal candidiasis in patients infected with HIV: A critical reassessment. AIDS Res Hum Retroviruses 1999;15:1405-2.
Meless D, Ba B, Faye M, Diby JS, Nzore S, Datte S, et al
. Oral lesions among HIV infected children on antiretroviral treatment in West Africa. Trop Med Int Health 2014;19:246-55.
Shanti RM, Aziz SR. HIV associated salivary gland disease. Oral Maxillofac Surg Clin North Am 2009;21;339-43.
Navazesh M, Mulligan R, Komaroff E, Redford M, Greenspan D, Phelan J. The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women. J Dent Res 2000;79:1502-7.
Nittayananta W, Chanowanna N, Jealae S, Nauntofte B, Stoltze K. Hyposalivation, xerostomia and oral health status of HIV-infected subjects in Thailand before HAART era. J Oral Pathol Med 2010;39:28-34.
Cavasin JC, Giovani EM. Xerostomy, dental caries and periodontal disease in HIV+patients. Braz J Infect Dis 2009;13:13.
Frontiers in clinical dentistry: Caries and periodontal disease—Symposium proceedings. Seattle, Washington, USA. J Dent Educ 1998;62:749-889.
Hauk MJ, Moss ME, Weinberg JE, Berkowitz RJ. Delayed Tooth Eruption: Association with severity of HIV infection. Pediatr Dent 2003;23:260-2.
Anusavice KJ. Management of dental caries as a chronic infectious disease. J Dent Educ 1998;62:791-802.
Slatyer KL, Marrie TJ. Treatment of recurrent aphthous ulcers in an HIV patient – An emerging use for pentoxifylline. Can J Infect Dis 1998;9:189-90.
Gomes RS, daCosta JE, Loyola AM, de Araujo NS, de Araujo VC. Immunohistochemical study of linear gingival erythema from HIV-positive patients. J Periodontal Res 1995;30:355-9.
Zabos GP. Meeting primary oral health care needs of HIV-infected women. Am J Public Health 1999;89:818-9.
Poonam RS, Srivastava G, Theruru K. Oral manifestations of human immunodeficiency virus in children: An institutional study in highly active antiretroviral centre. J Oral Maxillofac Pathol 2012;16:195-202.
Ahmed A, Bugaje MA, Bubadoko AA, Ameh E. Management of AIDS associated Kaposi sarcoma in Nigerian children: A case series and review of literature. J Natl Med Assoc 2012;104:385-9.
Shiboski CH, Palacio H, Neuhaus JM, Greenblatt RM. Dental care access and use among HIV-infected women. Am J Public Health 1999;89:834-9.
Dental management of the HIV-infected patient. J Am Dent Assoc 1995;(Suppl):1-40.
Glick M, Abel SN, Muzyka BC, DeLorenzo M. Dental complications after treating patients with AIDS. J Am Dent Assoc 1994;125:296-301.
Pediatric Antiretroviral Therapy Guidelines 2013, www.nacoonline.org. [Last accessed on 2014 Mar 14].
Fine DH, Tofsky N, Nelson EM, Schoen D, Barash A. Clinical implications of the oral manifestations of HIV infection in children. Dent Clin North Am 2003;47:159-74.
Leão JC, Ribeiro CMB, Carvalho AAT, Frezzini C, Porter S. Oral complications of HIV disease. Clinics 2009;64:459-70.
Williams IG. Enfuvirtide (Fuzeon): The first fusion inhibitor. Int J Clin Pract 2003;57:890-7.
Antiretroviral drugs used in the treatment of HIV infection, 2016, U.S. Food and Drug Administration, www.fda.gov. [Last updated on 2018 May 14].
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al
. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505.
Stankov MV, Behrens GM. HIV-therapy associated lipodystrophy: Rxperimental and clinical evidence for the pathogenesis and treatment. Endocr Metab Immune Disord Drug Targets 2007;7:237-49.
Coogan MM, Greenspan J, Challacombe SJ. Oral lesions in infections with human immunodeficiency virus. Bull World Health Organ 2005;85:700-6.
Brechtl JR, Breitbart W, Galietta M, Krivo S, Rosenfeld F. The use of Highly active antiretroviral therapy (HAART) in patients with advanced HIV infection: Impact of medical, palliative care and quality of life Outcomes. J Pain Symptom Manage 2001;21:41-51.
Geocze L, Mucci S, De Marco MA, Nogueira-Martins LA, de Albuquerque Citero V. Quality of life and adherence to HAART in HIV infected patients. Rev Saude Publica 2010;44:1-6.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]