Home » Volumes » Volume 47 January/February 2014 » Prevalence and factors associated with lipodystrophy in AIDS patients

Prevalence and factors associated with lipodystrophy in AIDS patients

Lunara Basqueroto Della Justina[1] Magali Chaves Luiz[2] Rosemeri Maurici[1] Fabiana Schuelter-Trevisol[1] [3]

[1]Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Tubarão, SC [2]Centro de Doenças Infecciosas, Hospital Nereu Ramos, Florianópolis, SC [3]Centro de Pesquisas Clínicas, Hospital Nossa Senhora da Conceição, Tubarão, SC

DOI: 10.1590/0037-8682-0240-2013


ABSTRACT

Introduction:

The published literature shows an increased occurrence of adverse events, such as human immunodeficiency virus (HIV)-associated lipodystrophy syndrome, that are associated with the continuous use of antiretroviral therapy. This study was performed to estimate the prevalence and factors associated with lipodystrophy in acquired immune deficiency syndrome (AIDS) patients.

Methods:

We conducted a cross-sectional study between October 2012 and February 2013. The sample consisted of patients with AIDS who attended the Outpatient Treatment Center for Infectious Diseases at Nereu Ramos Hospital, Florianópolis, State of Santa Catarina, Brazil. We collected information on demographics, lifestyle, HIV infection, and clinical aspects of the disease. Self-reported signs of lipodystrophy and body measurements were used for lipodystrophy diagnosis.

Results:

We studied 74 patients (mean age 44.3±9.2 years; 60.8% men). Among the patients, 45.9% were smokers, 31.1% consumed alcoholic beverages, and 55.4% were sedentary. The prevalence of lipodystrophy was 32.4%, and sedentary subjects had a higher prevalence of lipodystrophy compared with physically active individuals.

Conclusions:

The prevalence of lipodystrophy was 32.4%. Physical activity was considered an independent protective factor against the onset of HIV-associated lipodystrophy.

Key words: Lipodystrophy; HIV; HIV-associated lipodystrophy syndrome; Acquired immune deficiency syndrome; Prevalence

INTRODUCTION

The development of antiretroviral drugs and subsequent access to combined antiretroviral therapy contributed to the decline in morbidity and mortality rates associated with acquired immune deficiency syndrome (AIDS), resulting in an increased life expectancy and improved quality of life for people living with human immunodeficiency virus (HIV)1,2.

With the reduction in mortality rates, AIDS has become a chronic and treatable disease. However, along with these advances, findings in the published literature show an increased occurrence of adverse events associated with the continuous use of antiretroviral therapy, such as HIV-associated lipodystrophy syndrome35.

HIV-associated lipodystrophy syndrome is characterized by a set of morphological changes in body-fat distribution and/or metabolic abnormalities, including lipodystrophy, dyslipidemia, insulin resistance, and hyperglycemia68.

Lipodystrophy is characterized by a redistribution of body fat in individuals living with HIV and can be classified into three categories: lipohypertrophy, lipoatrophy, and mixed syndrome. Lipohypertrophy is the accumulation of fat in the abdominal and dorsal-cervical areas and breasts. Lipoatrophy or peripheral atrophy refers to the loss of subcutaneous fat in the face, buttocks, and upper and lower limbs and the possible presentation of prominent blood vessels. Mixed syndrome refers to a combination of lipohypertrophy and lipoatrophy7.

The pathogenesis of lipodystrophy in people living with HIV is multifactorial and still not fully understood. This disease is most likely a result of the interaction between antiretroviral therapy, virus infection, genetic factors, and the lifestyle of the individual8,9. The association between lipodystrophy and antiretroviral therapy is well established in the scientific literature, especially when protease inhibitors and reverse transcriptase inhibitors are used10,11. However, some studies have described cases of HIV-positive individuals who were not treated with antiretroviral therapy but had changes in body fat composition1214.

Changes in body fat composition have been characteristic of HIV-infected individuals since the beginning of the epidemic. Weight loss was one of the major signs associated with HIV infection in the era before the emergence of combined antiretroviral therapy. Lipodystrophy has become new physical evidence of HIV infection1,15,16.

HIV-associated lipodystrophy can generate psychological and social problems that arise from dissatisfaction with body image, as well as induce treatment discontinuation. The changes in physical appearance that are associated with lipodystrophy in individuals living with HIV have a negative psychosocial impact, such as causing low self-esteem, social isolation, and depression, that affects the individual’s quality of life and may impair adherence to treatment16,17.

This study was performed to estimate the prevalence and factors associated with lipodystrophy in patients with AIDS who were treated at a referral hospital for infectious diseases.

METHODS

This study was approved by the Research Ethics Committee of the University of Southern Santa Catarina (code number 12.171.4.06.III).

This was a cross-sectional, epidemiological study that was conducted between October 2012 and February 2013 in the Infectious Disease Center of Nereu Ramos Hospital, Florianópolis, State of Santa Catarina, Brazil. The population consisted of patients with HIV undergoing antiretroviral therapy who were aged 18 years and over (both genders) and attending the outpatient center. The exclusion criteria were the following: pregnancy, incomplete clinical data (missing lab test values or incomplete medical records), severe disease either associated with or without HIV infection, previous surgery (e.g., liposuction or liposculpture), and the use of methylmethacrylate to correct facial lipoatrophy.

According to the data from the health care center, 350 registered patients, including those who had discontinued treatment, fulfilled the criteria. Study participants were recruited among the patients attending medical appointments for treatment during the study period in one outpatient center (convenience sample). The patients were invited to participate in the study before or after consultation with a physician. Written informed consent was obtained from all participants for this study. Consenting patients were interviewed and underwent physical assessment.

The instrument for data collection consisted of a combination of interviews and data collection forms that included demographic data (gender, age, ethnicity, and education level), lifestyle (smoking, alcohol consumption, and physical activity), and clinical aspects of HIV infection that were obtained from medical records (CD4+ T-cell count, viral load, serum lipid profile and fasting glucose, time elapsed since HIV diagnosis, classes of antiretroviral drugs currently used, and duration of antiretroviral therapy). Indicators of lipodystrophy self-perception and anthropometric measurements were also included.

The CAGE questionnaire was administered to the HIV-infected individuals who said that they consumed or had consumed alcohol. The levels of physical activity were obtained during the interview by administering the International Physical Activity Questionnaire – Short Form (IPAQ-SF), version 8. The obtained data were classified according to Sjostrom et al.18. For this study, we used the following classification: sedentary individuals, i.e., those with a low level of physical activity, and physically active individuals, i.e., those with moderate and/or elevated levels of physical activity whose moderate-to-vigorous-intensity physical activity lasted at least 150min per week.

Right-side anthropometric measurements were taken twice, and the mean value was used in all analyses. The circumference measurements of the arm, neck, waist, and hip were obtained according to the reference standards suggested by Heyward and Stolarczyk19. An inelastic measuring tape with a 1-mm resolution was used to perform the measurements.

We used a scientific caliper (Cescorf®, 0.1 mm – Cescorf Equipamentos para Esporte Ltda, Porto Alegre, Rio Grande do Sul, Brazil) to measure the skinfold thickness at the following sites: biceps, triceps, subscapular site, iliac crest, midaxilla, abdomen, and calf according to the standards suggested by Guedes20, which were also used in other studies12,48,54. The anthropometric measures were classified using the lowest and highest percentiles (25 and 75, respectively).

A digital scale with a stadiometer (Wiso® W721) was used to determine the body mass and height following the anthropometric measurement techniques recommended by Fernandes Filho21. Body mass index (BMI) was used to assess the nutritional status at the cutoff points that were established by the World Health Organization22.

Currently, no consensus regarding the reference method for the diagnosis of HIV-associated lipodystrophy exists. Usually, lipodystrophy is self-reported by the HIV patient and is associated with body measurements12,14. We considered patients with lipodystrophy as those who had at least two self-perceived body changes that were consistent with the anthropometric measures in that body area.

The collected data were entered into EpiData version 3.1 (EpiData Association, Odense, Denmark), and statistical analyses were performed using the Statistical Package for Social Sciences® (SPSS for Windows v. 18, Chicago, IL, USA).

Crude and adjusted prevalence ratios were estimated, and the modified Poisson regression with a robust estimator was used to control over-confounding variables. Confounding factors were selected among the variables associated with physical activity in the bivariate analysis (p-value<0.20) and from those described as such in the literature. The level of confidence was set at 5%.

RESULTS

Of the 97 patients who were initially recruited, 88 were eligible for the study, but 14.8% refused to participate. We studied 74 patients with AIDS who attended the Outpatient Treatment Center for Infectious Diseases at Nereu Ramos Hospital during the study period.

The mean age was 44.3±9.2 years, the ages ranged from 20-64 years, and participants were predominantly Caucasian men. The mean number of years of education was 9.0±3.4 years. Table 1 shows the sociodemographic characteristics and lifestyle habits of the study participants.

TABLE 1 – Sociodemographic characteristics and lifestyles of the study participants (n=74). 

Variables n % 95% CI
Gender
 male 45 60.8 48.6 – 71.6
 female 29 39.2 28.4 – 51.4
Age (years)
 19 – 34 9 12.1 5.5 – 20.3
 35 – 50 46 62.2 51.4 – 73.0
 > 50 19 25.7 16.2 – 35.1
Ethnicity
 caucasians 68 91.9 85.3 – 97.3
 non-caucasians 6 8.1 2.7 – 14.9
Education (years)
 0 – 8 35 47.3 36.5 – 58.1
 > 8 39 52.7 41.9 – 63.5
Smoking
 smoker/ex-smoker 34 45.9 35.1 – 58.1
 non-smoker 40 54.1 41.9 – 64.9
Alcohol consumption
 yes 23 31.1 20.3 – 41.9
 no 51 68.9 58.1 – 79.7
BMI (kg/m2)
 < 18.5 2 2.7 0.0 – 6.8
 18.5 – 24.9 45 60.8 50.7 – 71.6
 25 – 29.9 18 24.3 14.9 – 35.1
 ≥ 30 9 12.2 5.4 – 18.9
Physical activity
 physically active 33 44.6 33.8 – 55.4
 sedentary 41 55.4 44.6 – 66.2

BMI: body mass index; CI: confidence interval.

Among the participants who reported consuming alcoholic beverages, 6 (8.1%) were classified as alcoholics according to the CAGE questionnaire. Among the physically active subjects, 28 (37.8%) were engaged in moderate physical activity and 5 (6.8%) were involved in high-level physical activity. Table 2shows the clinical characteristics and HIV infection status of the study participants.

TABLE 2 – Clinical characteristics and HIV infection status of the study participants (n=74). 

Variables n % 95% CI
Time since diagnosis (years)
 <3 8 10.8 4.1 – 17.6
 3 – 5 17 23.0 13.5 – 32.4
 > 5 49 66.2 55.4 – 77.0
Time on ART (years)
 <3 12 16.2 8.1 – 24.3
 3 – 5 18 24.3 14.9 – 33.8
 > 5 44 59.5 48.6 – 70.3
ART regimens
 2 NRTIs + 1 NNRTI 35 47.3 36.5 – 58.1
 2 NRTIs + 1 PI 32 43.2 32.4 – 54.1
 Other 7 9.5 2.7 – 17.6
CD4+ T-cells
 < 350 cells/mm3 22 29.7 20.3 – 40.5
 ≥350 cells/mm3 52 70.3 59.5 – 79.7
Viral load
 undetectable 63 85.1 77.0 – 93.2
 detectable 11 14.9 6.8 – 23.0

ART: antiretroviral therapy; CD4+ T-cells: T lymphocytes with surface CD4 receptors; CI: Confidence interval. NRTIs: nucleoside analog reverse-transcriptase inhibitors; NNRTIs: non-nucleoside reverse transcriptase inhibitors; PI: protease inhibitor.

According to the date registered in the medical records, the mean time since HIV infection diagnosis was 9.1±5.9 (median 8) years and ranged from 1-22 years.

The mean CD4+ T-cell count among the study participants was 491±249 cells/mm3 (median 448 cells/mm3, range 29-1269 cells/mm3). The limit of viral load detection was 50 copies/mL (undetectable), which was reached in 85% of the sample. Considering only those participants with a detectable viral load (n=11), the minimum and maximum viral loads were 448 and 72,416 copies/mL, respectively (average 22,225±29,606 copies/mL; median 4,494 copies/mL).

With regard to drug treatment, the mean duration of antiretroviral therapy was 7.9±5.2 years (median 7 years, range 1-20 years).

The prevalence of self-reported lipodystrophy was 51.4%, whereas the results of anthropometric measurements showed a prevalence of 66.2%. The incidence of lipodystrophy, as defined by at least two changes in body fat distribution as verified by self-reports and objective measurements, was 32.4%. With regard to the classification of lipodystrophy, 62.5% individuals had lipoatrophy, 29.2% had a mixed form, and 8.3% had lipohypertrophy.

Table 3 shows the distribution of the investigated variables according to the presence or absence of lipodystrophy.

TABLE 3 – Distribution of the investigated variables according to the presence or absence of lipodystrophy (n=74). 

Variables Lipodystrophy PR (95% CI) P-value
presence n=24) absence (n=50)
Gender 0.204
 male 17 70.8 28 56.0 1.15 (1.09-1.49)
 female 7 29.2 22 44.0 1.0
Age groups (years) 0.039
 19 – 34 4 16.6 5 10.0 1.0
 35 – 50 10 41.7 36 72.0 0.80 (0.56-1.13)
 > 50 10 41.7 9 18.0 1.09 (0.73-1.61)
Ethnicity 0.291
 whites 23 95.8 45 90.0 1.19 (0.86-1.63)
 non-whites 1 4.2 5 10.0 1.0
Education (years) 0.499
 0 – 8 10 41.7 25 50.0 0.93 (0.75-1.15)
 > 8 14 58.3 25 50.0 1.0
Smoking 0.137
 yes 14 58.3 20 40.0 1.18 (0.95-1.46)
 no 10 41.7 30 60.0 1.0
Alcohol abuse 0.366
 yes 3 12.5 3 6.0 1.21 (0.80-1.83)
 no 21 87.5 47 94.0 1.0
Physical activity 0.001
 physically active 4 16.7 29 58.0 0.69 (0.57-0.84)
 sedentary 20 83.3 21 42.0 1.0
Time since diagnosis (years) 0.311
 <3 6 12.0 2 8.3 1.0
 3 – 5 14 28.0 3 12.5 0.71 (0.15-3.43)
 > 5 30 60.0 19 79.2 1.55 (0.44-5.42)
Time on ART (years) 0.415
 <3 9 18.0 3 12.5 1.0
 3 – 5 14 28.0 4 16.7 0.89 (0.24-3.28)
 > 5 27 54.0 17 70.8 1.55 (0.54-4.41)
ART regimens 0.939
 2 NRTIs + 1 NNRTI 12 50.0 23 46.0 1.06 (0.73-1.53)
 2 NRTIs + 1 PI 10 41.7 22 44.0 1.03 (0.71-1.49)
 Other 2 8.3 5 10.0 1.0
CD4+ T-cells 0.644
 <350 cells/mm3 8 33.3 14 28.0 1.0
 ≥350 cells/mm3 16 66.7 36 72.0 0.95 (0.75-1.20)
Viral load** 0.768
 ≤ 50 copies/mL 20 83.3 43 86.0 0.96 (0.70-1.30)
 > 50 copies/mL 4 16.7 7 14.0 1.0

ART: antiretroviral therapy; NRTIs: nucleoside analog reverse-transcriptase inhibitors; NNRTIs: non-nucleoside reverse transcriptase inhibitors; PI: protease inhibitor; CD4+ T-cells: T lymphocytes with surface CD4 receptors; BMI: Body mass index.

A statistically significant association was found between physical activity and lipodystrophy. Sedentary subjects had a higher prevalence of lipodystrophy compared with physically active individuals.

There was no difference between the lipid and glycemic profiles related to the presence or absence of lipodystrophy in patients was observed. The results are shown in Table 4.

TABLE 4 – Metabolic profile of the study participants according to the presence or absence of lipodystrophy (n =74). 

Total Mean (DP) Variation Lipodystrophy P-value*
presence (n=24) absence (n=51)
Cholesterol 183.5 (48.9) 67 – 399 173.9 188.1 0.178
HDL 53.1 (32.1) 21 – 270 53.7 52.8 0.930
LDL 105.1 (46.1) 24 – 321 99.2 108.0 0.389
Triglycerides 153.4 (87.6) 33 – 608 155.5 153.1 0.895
Blood glucose 91.7 (17.1) 44 – 204 90.6 92.2 0.649

*Student’s t-test. SD: standard deviation; HDL: high-density lipoprotein; LDL: low-density lipoprotein.

Table 5 presents the results of the multivariate analysis performed to control for confounding factors. Physical activity was an independent, protective factor against the onset of lipodystrophy in patients with AIDS.

TABLE 5 – Multivariate analysis controlling for the confounding factors associated with lipodystrophy (n=74). 

Variables PR* (95% CI) P-value
Gender 1.66 (0.84 – 3.28) 0.147
Age (years) 1.01 (0.97 – 1.04) 0.708
Smoking 1.10 (0.58 – 2.08) 0.770
Physical activity 0.27 (0.10 – 0.75) 0.012
Time since diagnosis (years) 1.02 (0.98 – 1.07) 0.287

PR: prevalence ratio, CI: confidence interval; HIV: human immunodeficiency virus;

*Modified Poisson regression with robust estimator.

DISCUSSION

The prevalence of lipodystrophy in this study was 32.4%. Brazilian studies that estimated the prevalence of lipodystrophy in AIDS patients undergoing antiretroviral therapy revealed that the prevalence ranged from 32.4-67.9%23,24. In a systematic review of Brazilian studies on lipodystrophy, the weighted average of the prevalence of people living with HIV was 53.5%25. Tien and Grunfeld26 conducted a review of international studies on lipodystrophy in people living with HIV and found that the prevalence ranged from 30-62%. The large variability in the prevalence rates may be attributed to the use of different diagnostic methods and the lack of consensus on the characterization of lipodystrophy, as well as heterogeneity within the study population.

The determination of the prevalence and incidence of HIV-associated lipodystrophy is complex because no universal consensus regarding the criteria for its diagnosis exists and lipodystrophy is described differently throughout the literature. Imaging tests, such as ultrasound, dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and nuclear magnetic resonance imaging, are also used in the diagnosis of HIV-associated lipodystrophy. However, they are costly and difficult to access in the public health care system.

In this study, the diagnosis of lipodystrophy was based on agreement between the patient self-report and anthropometric measurements, which are criteria that were also used in other studies12,36,48,54. The prevalence of HIV-associated lipodystrophy was found to be 51.4% when only the patients’ self-reports were considered. Studies conducted by Sanches et al.16, Smith27, and De Carvalho et al.28 also used the patients’ self-reports as the single method for diagnosis of HIV-associated lipodystrophy and revealed prevalences of 47.6%, 40.5%, and 50.9%, respectively. It is important to emphasize the subjectivity of the self-report method because it depends on the patient’s perception. When the prevalence of lipodystrophy was determined using anthropometric measurements, 66.2% of the study participants showed changes in body fat distribution. Studies investigating the prevalence of HIV-associated lipodystrophy using anthropometry combined with other methods were found, but they did not mention the incidence of lipodystrophy that was found by each method, only the overall result12,29. The different methods that are used for lipodystrophy diagnosis do not allow for reproducible studies and/or comparison of the data obtained by the different techniques.

Anatomical redistribution of body fat occurred in the following decreasing order of predominance: lipoatrophy, mixed-form, and lipohypertrophy. This finding is in agreement with the studies by Trinca et al.29, Gasparotto et al.30, and Signorini et al.31.

Lipoatrophy is more frequent than lipohypertrophy in patients with HIV-associated lipodystrophy. In a study by Cabrero et al.32, lipoatrophy, followed by lipohypertrophy, was the most common alteration reported by individuals with lipodystrophy. Hendrickson et al.33 found that lipoatrophy was one of the most common metabolic changes associated with antiretroviral therapy. Lipohypertrophy is linked to the accumulation of abdominal fat, especially intra-abdominal fat, and is associated with metabolic problems, such as insulin resistance and metabolic syndrome, which increase the risk of cardiovascular disease and diabetes mellitus34,35.

In this study, no difference in the lipid profile between the groups of patients with and without lipodystrophy was observed. This finding could be due to the limited sample size, coupled to the fact that the majority of patients in this study had levels of total and fractionated cholesterol, triglycerides, and blood glucose within the normal range.

The prevalence of lipodystrophy that was found in this study was higher in the 35-50- and >50-year age groups. This finding is similar to that found in the published literature, in which the highest frequency of lipodystrophy was reported in older age groups14,19,36. It is known that changes in body composition among older, HIV-negative individuals are related to the aging process, which results in decreased subcutaneous adipose tissue and increased body fat in the central region. Although subcutaneous fat decreases, the total fat mass tends to increase with age, and lean mass decreases concomitantly with an increase in body fat22,37. It should be noted that, in HIV-infected individuals, aging may be related to the AIDS classification and duration of antiretroviral therapy, which is a known risk factor for the onset of lipodystrophy14,38. The research design that was used for this study does not allow inferences to be made regarding correlations between HIV-related lipodystrophy and aging.

Changes in body fat distribution in patients with AIDS are among the major complications of the use of antiretroviral therapy. Among the antiretroviral therapy components, protease inhibitors and reverse transcriptase inhibitors, as well as the exposure time to antiretroviral therapy6,10, have been implicated as the cause of HIV-associated lipodystrophy. In the present study, no association was found between the presence of lipodystrophy in HIV-infected individuals and length of antiretroviral therapy. Segatto et al.39investigated the association between the use of antiretroviral therapy and the presence of lipodystrophy and found that the longer-duration treatment group had a higher proportion of lipodystrophy. Signorini et al.31 evaluated the body fat content in HIV-infected individuals according to the duration of antiretroviral therapy and found that the group that had undergone more than one year of treatment had 11 mm of additional fat in the visceral compartment content compared with those who had undergone less than one year of treatment. Similarly, other studies have reported an association between the presence of lipodystrophy and longer exposure to antiretroviral therapy, suggesting a temporal relationship between the use of pharmacological therapy and the emergence of lipodystrophy13,40.

This study showed a higher frequency of lipodystrophy in individuals who had been diagnosed with HIV for a longer period of time. These data are consistent with the published literature, which states that patients with a longer duration of HIV infection had higher prevalence rates of lipodystrophy12,13,39,40. The deleterious effects of HIV infection that are related to the onset of lipodystrophy correspond to permanent activation of inflammatory cytokines and increased oxidative stress, which are responsible for promoting apoptosis of T-cells and involved in the induction mechanism of tumor necrosis factor-alpha (TNF-α)4143.

The influence of the use of antiretroviral therapy on the onset of lipodystrophy in HIV-infected individuals could not be analyzed in this study because all sampled patients were undergoing antiretroviral therapy. Changes in body fat distribution have been reported in HIV-infected individuals who were not exposed to antiretroviral therapy. In a study conducted by Diehl et al.13, lipodystrophy was observed in 27% of HIV-infected individuals who had never undergone antiretroviral therapy (ART). Similar results were obtained in a study by Alencastro et al.12. Not all surveyed patients had HIV-associated lipodystrophy, which suggests that the onset of lipodystrophy varies with respect to the therapeutic regimen, treatment duration, and factors related to lifestyle, such as physical activity.

According to previously published studies and the recommendations of the Ministry of Health, physical activity and exercise are among the therapeutic interventions that can be used to prevent and treat the symptoms and complications of chronic HIV infection and the adverse events that are associated with the use of ART4447.

Florindo et al.48 studied the relationship between physical activity, as assessed using the Baecke questionnaire, and body fat in people living with HIV undergoing ART and found that physical activity aids in preventing the accumulation of central fat. Ramírez-Marrero et al.47 conducted a study in HIV-infected individuals undergoing ART and found an association between physical activity and body composition. Their findings revealed that physically active individuals exhibited lower central body fat and total body fat compared with sedentary subjects.

This study showed that there was a high incidence of sedentary lifestyle among the study population. The physical activity levels were measured by the IPAQ; however, according to a systematic review by Schuelter-Trevisol et al.49, physical activity levels vary according to the measurement method used. They found that HIV-positive patients showed inactivity or sedentary lifestyle percentages ranging from 19-73%. Despite the wide range of direct and indirect methods for measuring physical activity, it is believed that the IPAQ that was used in this study is one of the most appropriate tools for epidemiological studies and has been validated in several countries, which allows for comparison with other studies and reproducibility of the method. The IPAQ was designed to measure physical activity throughout an entire day, including leisure time, work, travel, and domestic chores. Moreover, it has the benefit of being inexpensive and easy to use and is recommended by the World Health Organization17,50.

Studies have demonstrated the beneficial effects of regular physical activity, including improved metabolic profile50, body composition, and quality of life51,52, in HIV-infected individuals. In the present study, physical activity was shown to be an independent protective factor against the onset of lipodystrophy in AIDS patients. Furthermore, sedentary subjects had a higher incidence of lipodystrophy compared with physically active individuals. It was observed that 58% of subjects in the non-lipodystrophic group were physically active, whereas only 16.7% were physically active in the lipodystrophic group. This finding is in agreement with the studies by Domingo et al.53, Segatto et al.39, and Schuelter-Trevisol et al.54, who investigated the association between physical activity and lipodystrophy in HIV-infected individuals and found a statistically significant association between physical activity levels and lipodystrophy, with physically active individuals exhibiting a lower incidence of lipodystrophy than those living a sedentary lifestyle. According to Segatto et al.39, physically active HIV-infected individuals were 79% less likely to have lipodystrophy than sedentary individuals.

It should be noted that daily physical activity could also result in significant energy expenditure. Individuals with regular physical activity at work, at home, and during leisure time that requires caloric expenditure are also considered physically active. Thus, a sedentary lifestyle is not just related to a lack of regular physical exercise.

The Ministry of Health44 recommends performing at least 30min of moderate physical activity five times a week or 20min of vigorous physical activity three times a week for people living with HIV and AIDS.

During the period of data collection, a smaller number of patients attended the outpatient center than the estimated number that was based on registered records, which limited the sample size and, consequently, the statistical analysis. The external validity of this study is limited because it was an observational study of a sample of patients who attended the outpatient treatment center. In addition, the cross-sectional design does not prove causality. However, the findings from this study may be used for comparison, evaluation, and monitoring of individuals living with HIV in clinical practice.

The overall prevalence of lipodystrophy was 32.4% among the participants in this study. Physical activity was considered an independent protective factor against the onset of HIV-associated lipodystrophy.

In conclusion, the findings from this study suggest that physical activity should be recommended as a therapeutic strategy for the prevention and treatment of lipodystrophy in people living with HIV and AIDS.

REFERENCES

1. Alencar TMD, Nemes MIB, Velloso MA. Transformações da “aids aguda” para a “aids crônica”: percepção corporal e intervenções cirúrgicas entre pessoas vivendo com HIV e aids. Cienc Saude Coletiva 2008; 13: 1841-1849. [ Links ]

2. Palella Jr FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338:853-860. [ Links ]

3. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356:1423-1430. [ Links ]

4. Louie M, Markowitz M. Goals and milestones during treatment of HIV-1 infection with antirretroviral therapy: a pathogenesis-based perspective. Antiviral Res 2002; 55:15-25. [ Links ]

5. Valente AM, Reis AF, Machado DM, Succi RC, Chacra AR. Metabolic alterations in HIV-associated lipodystrophy syndrome. Arq Bras Endocrinol Metabol 2005; 49:871-881. [ Links ]

6. Batterham MJ, Garsia R, Greenopa PA. Dietary intake, serum lipids, insulin resistance and body composition in the era of highly active antiretroviral therapy ‘Diet FRS Study’. AIDS 2000; 14:1839-1843. [ Links ]

7. Bedimo RJ. Body-fat abnormalities in patients with HIV: progress and challenges. J Int Assoc Physicians AIDS Care (Chic) 2008; 7:292-305. [ Links ]

8. Lichtenstein KA. Redefining lipodystrophy syndrome: risks and impact on clinical decision making. J Acquir Immune Defic Syndr 2005; 39: 395-400. [ Links ]

9. Martinez E, Mocroft A, Garcia-Viejo MA, Perez-Cuevas JB, Blanco JL, Mallolas J, et al. Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study. Lancet 2001; 357:592-598. [ Links ]

10. Carr A, Samaras K, Chisholm D, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998; 351:1881-1883. [ Links ]

11. Villarroya F, Domingo P, Giralt M. Lipodystrophy associated with highly active anti-retroviral therapy for HIV infection: the adipocyte as a target of anti-retroviral-induced mitochondrial toxicity. Trends Pharmacol Sci 2005; 26:88-93. [ Links ]

12. Alencastro PR, Wolf FH, Schuelter-Trevisol F, Ikeda ML, Brandão ABM, Barcellos NT, et al. Characteristics associated to lipodystrophy syndrome among HIV-infected patients naïve and on antiretroviral treatment. J AIDS Clinic Res 2012; 3:1-9. [ Links ]

13. Diehl LA, Dias JR, Paes AC, Thomazini MC, Garcia LR, Cinagawa E, et al. Prevalência da Lipodistrofia Associada ao HIV em Pacientes Ambulatoriais Brasileiros: Relação com Síndrome Metabólica e Fatores de Risco Cardiovascular. Arq Bras Endrocrinol Metabol 2008; 52: 658-667. [ Links ]

14. Lichtenstein KA, Ward DJ, Moorman AC, Delaney KM, Young B, Palella Jr FJ, et al. Clinical assessment of HIV-associated lipodystrophy in an ambulatory population. AIDS 2001; 15:1389-1398. [ Links ]

15. Baril JG, Junod P, Leblanc R, Dion H, Therrien R, Laplante F, et al. HIV-associated lipodystrophy syndrome: A review of clinical aspects. Can J Infect Dis Med Microbiol 2005; 16:233-243. [ Links ]

16. Sanches RS, Mill J, Machado AA, Donadi EA, Morais Fernandes AP. Facial lipoatrophy: Appearances Are Not Deceiving. J Assoc Nurses AIDS Care 2009; 20:169-175. [ Links ]

17. Collins E, Wagner C, Walmsley S. Psychosocial impact of the lipodystrophy syndrome in HIV infection. AIDS Read 2000; 10:546-550. [ Links ]

18. Sjöström M, Ainsworth B, Bauman A, Bull F, Craig C, Sallis J. Guidelines for data processing and analysis of the International Physical Activity Questionnaire (IPAQ) – Short and Long Forms; 2005. [ Links ]

19. Heyward VH, Stolarczyk IM. Avaliação da composição corporal aplicada. São Paulo: Manole; 2000. [ Links ]

20. Guedes DP. Composição corporal: princípios, técnicas e aplicações. 2nd ed. Londrina: APEF; 1994. [ Links ]

21. Fernandes Filho J. A prática da avaliação física: testes, medidas e avaliação física em escolares, atletas e academias de ginástica. 2nd ed. Rio de Janeiro: Shape; 2003. [ Links ]

22. World Health Organization (WHO). Physical status: the use and interpretation of anthropometry. Technical Report Series. Geneva: WHO; 1995. [ Links ]

23. Ceccato MG, Bonolo PF, Souza Neto AL, Araújo FS, Freitas MI. Antiretroviral therapy-associated dyslipidemia in patients from a reference center in Brazil. Braz J Med Biol Res 2011; 44:1177-1183. [ Links ]

24. Monnerat BZ, Cerutti Junior C, Canicali SC, Motta TR. Clinical and biochemical evaluation of HIV-related lipodystrophy in an ambulatory population from the Hospital Universitário Cassiano Antonio de Morais, Vitória, ES, Brazil. Braz J Infect Dis 2008; 12:364-368. [ Links ]

25. Della Justina LB, Schuelter-Trevisol F. Prevalência de lipodistrofia associada ao HIV em estudos brasileiros: uma revisão sistemática da literatura; 2013. [no prelo]. [ Links ]

26. Tien PC, Grunfeld C. What is HIV-associated lipodydtrophy? Defining fat distribution changes in HIV infection. Curr Opin Infect Dis 2004; 17: 27-32. [ Links ]

27. Soares LR. Perfil antropométrico e distribuição da gordura corpórea relacionados ao risco cardiovascular em adultos vivendo com HIV/AIDS [Dissertation]. [São Paulo (SP)]: Faculdade de Medicina da Universidade de São Paulo; 2010. [ Links ]

28. Carvalho EH, Miranda Filho DB, Ximenes RA, Albuquerque MF, Melo HR, Gelenske T, et al. Prevalence of hyperapolipoprotein B and associations with other cardiovascular risk factors among human immunodeficiency virus-infected patients in Pernambuco, Brazil. Metab Syndr Relat Disord 2010; 8:403-410. [ Links ]

29. Trinca JR, Sprinz E, Lazzaretti RK, Hutz MH, Kuhmmer R, Almeida S, et al. SNPs in the APM1 gene promoter are associated with adiponectin levels in HIV-infected individuals receiving HAART. J Acquir Immune Defic Syndr 2010; 55:299-305. [ Links ]

30. Gasparotto AS, Sprinz E, Lazzaretti RK, Kuhmmer R, Silveira JM, Basso RP, et al. Genetic polymorphisms in estrogen receptors and sexual dimorphism in fat redistribution in HIV-infected patients on HAART. AIDS 2012; 26:19-26. [ Links ]

31. Signorini DJHP, Netto AMSO, Monteiro MCM, Signorini DH, Codeço CT, Bastos FI, et al. Diferenças ultrassonográficas da quantidade de gordura corporal e os antirretrovirais. Rev Assoc Med Bras 2012; 58:197-203. [ Links ]

32. Cabrero E, Griffa L, Burgos A, HIV Body Physical Changes Study Group. Prevalence and impact of body physical changes in HIV patients treated with highly active antiretroviral therapy: Results from a study on patients and physician perceptions. AIDS Patient Care STDS 2010; 24:5-13. [ Links ]

33. Hendrickson SL, Kingsley LA, Ruiz-Pesini E, Poole JC, Jacobson LP, Palella FJ, et al. Mitochondrial DNA halogroups influence lipoatrophy after highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2009; 51:111-116. [ Links ]

34. Guimarães MMM, Greco DB, Ribeiro-Oliveira Jr A, Penido MG, Machado LJC. Distribuição da gordura corporal e perfis lipídico e glicêmico de pacientes Infectados pelo HIV. Arq Bras Endocrinol Metab 2007; 51:42-51. [ Links ]

35. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005; 352:48-62. [ Links ]

36. Miller J, Carr A, Emery S, Law M, Mallal S, Baker D, et al. HIV lipodystrophy: prevalence, severity and correlates of risk in Australia. HIV Med. 2003; 4:293-301. [ Links ]

37. Hughes VA, Roubenoff R, Wood M, Frontera WR, Evans WJ, Singh MAF. Anthropometric assessment of 10-y changes inbody composition in the elderly. Am J Clin Nutr 2004; 80:475-482. [ Links ]

38. Mutimura E, Stewart A, Rheeder P, Crowther NJ. Metabolic function and prevalence of lipodystrophy in a population of HIV-infected african subjects receiving highly active antiretroviral therapy. J Acquir Defic Syndr 2007; 46:451-455. [ Links ]

39. Segatto AF, Freitas Junior IF, Santos VR, Alves KC, Barbosa DA, Portelinha Filho AM, et al. Lipodystrophy in HIV/AIDS patients with different levels of physical activity while on antiretroviral therapy. Rev Soc Bras Med Trop 2011; 44:420-424. [ Links ]

40. Ponte CMM. Distúrbios metabólicos associados à infecção pelo HIV/Aids: prevalência em pacientes ambulatoriais seguidos em hospital de referência do Estado do Ceará, Brasil [Dissertation]. [Fortaleza (CE)]: Universidade Federal do Ceará; 2010. [ Links ]

41. Aukrust P, Muller F, Svardal A, Ueland T, Berge RK, Froland SS. Disturbed glutathione metabolism and decreased antioxidants levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy-potential immunomodulatory effects of antioxidants. J Infect Dis 2003;188:232-238. [ Links ]

42. Bodasing N, Fox R. HIH-associated lipodystrophy: assessment and management. J Infect 2003; 46:87-93. [ Links ]

43. Carr A. HIV lipodystrophy: risk factors, pathogenesis, diagnosis and management. AIDS 2003; 17 (supp I):141-148. [ Links ]

44. Ministério da Saúde. Secretaria de Vigilância em Saúde. Programa Nacional de DST, Aids e hepatites virais. Recomendações para a prática de atividades físicas para pessoas vivendo com HIV e Aids. Brasília: Ministério da Saúde; 2012. [ Links ]

45. Lindegaard B, Hansen T, Hvid T, van Hall G, Plomgaard P, Ditlevsen S, et al. The effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus-infected patients with lipodystrophy. J Clin Endocrinol Metab 2008; 93:3860-3869. [ Links ]

46. Mutimura E, Crowther NJ, Cade TW, Yarasheski KE, Stewart A. Exercise training reduces central adiposity and improves metabolic indices in HAART-treated HIV-positive subjects in Rwanda: a randomized controlled trial. AIDS Res Hum Retroviruses 2008; 24:15-23. [ Links ]

47. Ramírez-Marrero FA, Smith BA, Meléndez-Brau N, Santana-Bagur JL. Physical and leisure activity, body composition, and life satisfaction in HIV-positive Hispanics in Puerto Rico. J Assoc Nurses AIDS Care 2004; 15:68-77. [ Links ]

48. Florindo AA, Latorre MRO, Jaime PC, Segurado AA. Leisure time physical activity prevents accumulation of central fat in HIV/AIDS subjects on highly active antiretroviral therapy. Int J STD AIDS 2007; 18:692-696. [ Links ]

49. Schuelter-Trevisol F, Wolff FH, Alencastro PR, Grigoletti S, Ikeda ML, Brandão AB, et al. Physical Activity: Do patients infected with HIV practice? How much? A systematic review. Curr HIV Res 2012; 10: 487-497. [ Links ]

50. Matsudo S, Araujo T, Matsudo V, Andrade D, Andrade E, Oliveira LC, et al. Questionário internacional de atividade física (IPAQ): Estudo de validade e reprodutibilidade no Brasil. Rev Bras Ativ Fis Saúde 2001; 6:5-18. [ Links ]

51. Ogalha C, Luz E, Sampaio E, Souza R, Zarife A, Neto MG, et al. A randomized, clinical Trial to evaluate the impact of regular physical activity on the quality of life, body morphology and metabolic parameters of patients with AIDS in Salavador, Brazil. J Acquir Immune Defic Syndr 2011; 57 (Suppl III):179-185. [ Links ]

52. Fillipas S, Cicuttini FM, Holland AE, Cherry CL. Physical activity participation and cardiovascular fitness in people living with immunodeficiency virus: a one-year longitudinal study. J AIDS Clinic Res 2013; S9:002. [ Links ]

53. Domingo P, Sambeat MA, Pérez A, Ordoñez J, Rodriguez J, Vázquez G. Fat distribution and metabolic abnormalities in HIV-infected patients on first combination antiretroviral therapy including stavudine or zidovudine: role of physical activity as a protective factor. Antivir Ther 2003; 8: 223-231. [ Links ]

54. Schuelter-Trevisol F, Alencastro PR, Ribeiro PAB, Wolff FH, Ikeda MLR, Barcellos NT, et al. Association of physical activity with lipodystrophy syndrome in HIV-infected patients. J AIDS Clinic Res 2012; 3:177. [ Links ]

Financial Support: Support Fund for the Maintenance and Development of Higher Education (FUMDES) for granting a Master’s scholarship.

Conflict of Interest: The authors declare that there is no conflict of interest.

Received: November 9, 2013; Accepted: January 28, 2014