Alterações corporais : terapia antirretroviral e síndrome da lipodistrofia em pessoas vivendo com HIV / AIDS 1

Objetivo: identificar os diferentes tipos de alterações morfológicas da síndrome da lipodistrofia (SL) em pacientes dos atendimentos ambulatoriais e relacioná-las ao esquema terapêutico utilizado. Método: estudo transversal, para o qual foram recrutados 60 pacientes com HIV e SL e 79 sem a SL, que consentiram entrevista e coleta de dados em prontuário. Resultados: a região mais acometida pela lipoatrofia foi a face; pela lipo-hipertrofia o abdome e pela forma mista as alterações em abdome, face, membros superiores e inferiores. Conclusão: dentre os esquemas terapêuticos, o composto pela zidovudina, lamivudina e efavirenz pareceu proteger contra a SL. A enfermagem pode atuar na identificação precoce das alterações, além de fornecer orientações e apoio aos pacientes acometidos pelas mudanças na imagem corporal.


Introduction
Lipodystrophy Syndrome (LS) is currently one of the most worrying problems resulting from antiretroviral therapy (ARVT) for combatting the human immunodeficiency virus (HIV).Its pathogenicity still not totally understood, it is observed in therapeutic regimens which include the antiretrovirals (ARV) in the classes of the Nucleoside Analog Reverse-Transcriptase Inhibitors (NARTI) and the Protease Inhibitors (PI) (1)(2) .
It is characterized principally by alterations in the distribution of body fat, such as the loss of peripheral subcutaneous tissue and increase of central fat, and by metabolic disorders such as dyslipidemia, insulin resistance and abnormal glucose homeostasis, which may contribute to the development of cardiovascular illnesses and diabetes mellitus (3)(4) .
Morphological abnormalities resulting from alterations in the distribution of fat are manifested in various ways.Lipoatrophy (loss of adipose tissue) is noted on the face, buttocks and limbs, in which the venous circulation becomes more evident.Fat accumulation (lipohypertrophy) is seen in the central abdominal region, in addition to deposits in the breasts and dorsocervical region, also called the "buffalo's hump" (5)(6) .
Fat loss and accumulation can occur simultaneously -in different regions of the body -in the same individual.
This is called the mixed form.About 50% of the patients receiving antiretroviral therapy are affected by body changes resulting from LS (7)(8) .Among Brazilian patients, the prevalence described was of 55% (9) .Despite the great success of drug therapy in reducing the patients' morbidity and mortality rates (10) , the effects of LS -in particular, those which cause alterations in body image -contribute to the appearance of stigma, problems in social activities and alterations in sexuality, among others, impacting on quality of life (11)(12) .
Nursing has been developing various studies concerning the effects of LS on patients, from identifying their perceptions about changes in appearance (13) , to testing interventions which help them to face these (14) .The periodicals in the area, however, do not provide detailed evidence on discriminating between the morphological abnormalities by anatomical region, correlated with the ARVT used.Providing nursing care for the HIV patient requires varying skills of health professionals, as they are dealing with a client group which presents a range of simultaneous needs.Particularly in relation to drug therapy, the nurse has the mission of informing the client about its benefits and the need for good compliance, as well as the possible side-effects and ways of controlling them, such that the patient feels safe in undergoing the treatment (15) .
Thus, this study aimed to identify the different types of morphological alterations from LS present in outpatients and relate them to the therapeutic regimen being used, so as to provide support for nursing professionals to be able to promote specialized care for this population's needs.

Statistical analysis
The results were analyzed using Fisher's exact test, with the help of the GraphPad InStat 3.01 program.
Associations with a probability of below 5% (p<0.05) were considered.

Results
Of the 60 patients with LS selected for the study, 40 (67%) were male and 20 (33%) female; 45 (75%) were Caucasian, 08 (13.33%) were Afro-Brazilian and undetectable.The lipidogram values of the patients with and without LS are shown in Table 1.
In the analysis of the most-affected body regions, the researchers verified the therapeutic regimens used.Table 3 shows the comparison of the therapeutic regimens most used by the patients with and without LS.

Discussion
The pathogenicity of LS has been under study for over 10 years, and various factors have been identified as contributing to its development, such as gender, age, duration and seriousness of infection with HIV-1 (2,16) , and the use of antiretroviral therapy (1)(2) , in addition to the influence of the inflammatory cytokine genes in patients with LS on ARVT (17) .
Of the alterations caused by LS, those which cause great difficulties for the patients are the alterations in body harmony negatively impacting on their daily activities (11) .In our study, the morphological abnormalities were described in 23 patients (38.33%) in the form of lipoatrophy, in 9 (15%) as signs of fat accumulation, and 28 patients (46.66%) in the mixed form.These prevalencies are close to a description which evaluated a sample of 1,348 patients (8) .
Lipoatrophy has been showed to be more frequent than lipohypertrophy (18) and the face is the mostaffected body region, followed by the lower limbs, the buttocks, and the upper limbs (18) .In the present study's stratification, the face was the most-affected region, although the authors did not identify differences of prevalence between the upper limbs (MMSS) and the lower limbs (MMII), neither lipoatrophy exclusive to the buttocks, which was only perceived in the mixed form of LS.In relation to lipohypertrophy, the abdomen was the most-affected body region, in line with other studies (2,8) , followed by the breast, dorsocervical region and thorax.
The most found mixed form was shown by the presence of lipohypertrophy of the abdomen and atrophy of the face, upper limbs and lower limbs.
Retroviral drugs' association with LS is incontestable and was described a long time ago.In view of this, an analysis was undertaken of the therapeutic combinations most used by the two groups of patients studied -with and without LS (Table 3).Thus, the therapeutic regimen made up by the combination of Zidovudine + Lamivudine + Efavirenz (AZT + 3TC + EFZ) was shown to be a protector against LS (p=0.0149).A study carried out with 100 patients who received this same therapeutic combination for 48 weeks and who were later evaluated using imaging exams -computerized tomography and DEXA -dual X-ray absorptiometry -confirms that this therapeutic regimen is not associated with significant morphological changes, as it resulted in a minimal and modest fat accumulation (19) .
The influence of NARTI class medications in the development of LS is predominantly reported through the use of Stavudine (d4T) (20) and of AZT, in lower intensity (21) .
When the authors analyzed each antiretroviral drug in isolation (Table 4), two drugs from the NARTI class -AZT and Lamivudine (3TC) -seemed to suggest protection against the development of LS (p<0.0001 and p=0.0103, respectively).However, the authors emphasize that a better investigation is necessary, including a thorough analysis of the therapeutic combinations used.In addition, consistent information was not found on the influence of 3TC on its own in the development of LS.Furthermore, there is a report of the combination of these two drugs in the development of morphological changes (22) .
According to the present study's data, a further two drugs in this class -Tenofovir (TDF) and Didanosine (ddI) seem to contribute to the development of LS (p=0.0427 and p=0.0432, respectively).The information on the role of ddI in LS are conflicting: one study states that this drug is independently associated with LS (23) and another, that the use of ddI is significantly associated with the depletion of mitochondrial DNA in the adipose tissue of patients with peripheral lipoatrophy, and that this may be reverted with discontinuation of use (24) .However, another study states that ddI does not contribute to peripheral lipoatrophy (25) .In relation to TDF, in contrast to what the present study's authors found, it seems there is a consensus in the literature that the substitution of d4T with TDF minimizes the risk of developing LS (20) , improving the recuperation of peripheral adipose tissue and in this way contributing to the reversal of lipoatrophy (26) .
Despite the PI class being widely related to LS (5) , the authors did not determine influences of these medications in the present study.
New antiretroviral drugs are being developed and used in the treatment against infection by HIV, and further studies will be necessary on their adverse effects over time.The authors understand that the fact that the study does not determine the exact length of treatment for each type of antiretroviral and/or therapeutic regimen -which can interfere in the development of LS -is a limitation on the study.
However, the authors can provide support for specialized nursing care for this client group, in regard to monitor their therapeutic regimens; identifying and intervening in both morphological changes and changes in their lipid profile, and providing psychosocial support in the face of changes in body image.
LS were selected at the Dyslipidemia Outpatient Department in the Special Unit for Treatment of Infectious Diseases at the Clinical Hospital of the Faculty of Medicine of Ribeirão Preto, part of the University of São Paulo, which exclusively attends patients with HIV-1, and is a regional center of excellence for this type of care.The study's inclusion criteria were: positive serology for HIV-1, age between 18 and 65 years, treatment with ARV for a minimum of 18 months and morphological alterations related to LS.The morphological alterations of the patients with LS were identified based on agreement between the patients' accounts, medical observations, and observations made by the researchers about body shape alterations.For the comparison group, the researchers selected 79 patients with positive serology for HIV-1, aged between 18 and 65, receiving ARV treatment for a minimum of 18 months and with no reference for any type of body change related to LS.

Table 1 -
Table 4 shows the comparison of each retroviral medication used by the patients with and without LS.Lipidogram values of the patients with HIV-1,

Table 2 -
LS morphological abnormalities' localization, according to body region UL: upper limbs; LL: lower limbs.