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Total Body Composition by DXA of 241 HIV-Negative Men and 162 HIV-Infected Men
Journal of Clinical Densitometry, vol. 8, no. 3, 287–292, 2005 © Copyright 2005 by Humana Press Inc. All rights of any nature whatsoever reserved. 1094-6950/05/8:287–292/$30.00 DOI: 10.1220/1094-6950
Original Article
Total Body Composition by DXA of 241 HIV-Negative Men and 162 HIV-Infected Men Proposal of Reference Values for Defining Lipodystrophy E. Bonnet,*,1,2 C. Delpierre,6 A. Sommet,1 F. Marion-Latard,3 R. Hervé,1 C. Aquilina,5 E. Labau,1 M. Obadia,1 B. Marchou,1 P. Massip,1 B. Perret,2 and J. Bernard4 1Unit of Infectious and Tropical Disease and 2INSERM U 563, Purpan Hospital, Toulouse, France; 3Unit of Sport Medicine and 4Unit of Rhematology, Rangueil Hospital, Toulouse, France; 5Unit of Dermatology, La Grave Hospital, Toulouse, France; and 6Unit of Epidemiology and Public Health, INSERM U558, Toulouse, France
Abstract The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIVinfected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value ± standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3 ± 0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier. Key Words: HIV; lipodystrophy; DXA; fat mass ratio; antiretroviral drugs; bone mineral density.
Intorduction
antiretroviral treatment [HAART]) has been recognized as one of the major long-term adverse effect of antiretroviral combinations (2,3). Osteopenia is also one of the main concerns for HIV-infected people; however the specific role of HIVdisease-related factors and anti-HIV treatment per se has to be clarified (4). Large discrepancies in lipodystrophy incidence reported in previous studies are the result of the lack of homogeneous criteria for the diagnosis of lipodystrophy (5). Greater use of DXA and the determination of standard values for fat mass distribution could improve early detection and diagnosis of lipodystrophy. However, no standard values of body composition by DXA are available for HIV-negative men. We compared body composition as measured by DXA in a large cohort of HIV-negative men to a cohort of HIV-infected
Dual-energy X-ray absorptiometry (DXA) is a reliable technic for measuring total-body and regional bone mineral and soft tissue composition (1). Its usefulness for measuring fat redistribution in metabolic diseases has become increasingly evident. Since 1996 to 1997, lipodystrophy (which is notably different from acquired immunodeficiency syndrome [AIDS]wasting syndrome described in human immunodeficiency virus [HIV]-infected patients before the era of highly active Received 11/04/04; Revised 01/21/04; Accepted 02/02/05. *Address correspondance to: E. Bonnet, Hôpital Purpan, Place du Docteur Baylac, 31059 Toulouse cedex, France. E-mail: bonnet.e@ chu-toulouse.fr
287
288 men followed in one university hospital in southern France. We believe this to be the largest group of such HIV-negative, normal men reported to date. The aims of our study were to define standard values for body composition in HIV-negative men, to compare these values to those of HIV-infected men, and to analyze factors associated with low bone mass and lipodystrophy as measured by DXA in HIV-infected men.
Patients and Methods We conducted a cross-sectional analysis on 403 men (age: 20–60 yr). Two-hundred forty-one men were HIV-negative volunteers without any medical or surgical history, needing neither therapies nor immobilization longer than 2 mo, designed as controls. One-hundred sixty-two men were HIVinfected outpatients at steady state, naïve (34 patients), or treated (128 patients), with or without clinical lipodystrophy, without current opportunistic disease, and not under prophylactic regimen. The controls have been selected at the time of a routine medical visit for evaluating ability to work and they all agreed to participate to a study designed to define normal values of bone mineral density (BMD) in French men. Because DXA gives a reproducible and precise fat mass percentage of the trunk, limbs, and total body (6), we measured a lipodystrophy index defined by the ratio of the trunk fat mass percentage over the lower limbs fat mass percentage. We defined it as the fat mass ratio (FMR = % of the trunk fat mass/% of the lower limbs fat mass). The two main reasons why we chose this index were that 80% of trunk fat mass is perivisceral and 98% of limbs fat mass is subcutaneous (7) and that lipodystrophy in HIV-people might be the result of a loss of subcutaneous fat mass, an accumulation in perivisceral fat mass, or both (2,8–11). We attempted to determine standard values for FMR according to the mean value ± standard deviations measured for HIV-negative men. The threshold chosen for defining lipodystrophy by DXA corresponded to the value for FMR above the mean value ± standard deviation measured for HIVnegative men. Clinical lipodystrophy was defined as a peripheral lipoatrophy with or without a central fat accumulation assessed by both patient and practitioner. Total-body bone mineral and soft tissue composition were measured by DXA with DPX-L (Lunar Corporation®) acquisition and analysis software 4.6. Markers used in this study for trunk and lower limbs that defined regions of interest were those indicated by the manufacturer. All subjects gave written informed consent. We compared body mass index (BMI) indicated in medical record, fat mass percentage (%FM), lean mass (LM), total BMD, and FMR between the whole population of the two groups and by age range, between naïve and treated patients, and between treated patients with clinical lipodystrophy and treated patients without clinical lipodystrophy. In the HIV group, we studied correlation among age, duration of seropositivity, duration of antiretroviral drugs use, CDC stages, viral Journal of Clinical Densitometry
Bonnet et al. load (determined by the Amplicor Monitor Roche® test, limit of detection: 20 copies/mL), CD4 cell count, BMD, and FMR at the time of DXA.
Statistical Analysis Means and standard deviations were determined for all variables. We compared controls and HIV-infected men classified by age range using two-way analysis of variance (ANOVA) and subgroups (naïve HIV-infected men, treated HIV patients, with or without clinical lipodystrophy) using ANOVA, according to age. We used descending stepwise linear regression to correlate BMD and FMR (dependent variables) to age, duration of HIV seropositivity, CDC stage, CD4 cell count, viral load, and duration of treatment for each antiretroviral compound (independent variables) at the time of DXA.
Results Controls The mean age was 39 ± 8 yr, the mean height was 176 ± 5 cm, the mean BMI was 25.4 ± 2.9. The mean FMR was 1.3 ± 0.2. Thus, standard values for FMR in HIV-negative men were between 1.1 and 1.5. An age effect was found for FMR and BMI, as FMR and BMI were higher for older men (p < 0.001 and p < 0.01, respectively). The mean BMD was 1.23 ± 0.08.
HIV-Infected Men The mean age was 39 ± 9 yr, the mean height was 175 ± 6 cm, and the mean BMI was 23.3 ± 3.2. The mean duration of seropositivity was 69.2 ± 58 mo. The mean duration of treatment was 33 ± 18 mo. Clinical stages according to the CDC classification were A for 97 patients, and B for 40 patients, and C for 25 patients. The mean viral load was 2.6 ± 1.5 log-copies/mL, the mean CD4 cell count was 485 ± 250/mm3 (data not presented in tables). There was no statistical difference in FMR and BMD according to the CDC stage, duration of seropositivity, viral load, or CD4 cell count at the time of DXA (Tables 1 and 2). As shown in Tables 1 and 2, when compared to controls, HIV-infected men had a lower BMD (1.15 vs 1.23, respectively; p < 0.0001) and a higher FMR (1.6 vs 1.3, respectively, p < 0.0001). The mean FMR was above the threshold defining lipodystrophy by DXA for HIV men. As shown for controls, the FMR and BMI were higher in older patients (p < 0.001 and p < 0.01, respectively). HIV-infected men also exhibited a lower BMI (p < 0.0001) and a lower percent fat mass (p < 0.0001). The total LM was identical in the two groups. As shown in Table 2, under the threshold value defining lipodystrophy by DXA, naïve HIV-infected men and controls had a similar FMR. Naïve HIV-infected men had a lower BMD and BMI. Among HIV-infected men, the FMR was significantly higher for those receiving HAART than for those who have never been treated (p < 0.05) and above the threshold defining lipodystrophy by DXA. BMD was slightly lower in treated HIV-infected men (p < 0.05), and the BMI was identical. Volume 8, 2005
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Table 1 Comparison of Athropometric and DXA Varibles by Age Groups Between Controls and Patients n Controls 21 HIV 19 Controls 106 HIV 76 Controls 91 HIV 49 Controls 23 HIV 18 Population effect Age effect Interaction
Age class (yr)
Height (cm)
20–29 20–29 30–39 30–39 40–49 40–49 50–60 50–60
176 174 177 176 175 174 175 173 NS p < 0.05 NS
BMI 24.5 21.8 24.9 23.1 25.9 23.8 26.4 24.1 p < 0.0001 p < 0.01 NS
% FM 19 10 21 14 21 15 23 16 p < 0.0001 p < 0.01 NS
FM (kg) 15 6.6 16.1 10 16.8 11.1 18.5 11.5 p < 0.0001 p < 0.01 NS
LM (kg)
FMR
BMD (g/cm2)
58 56.7 58.7 58.8 59.3 58.5 59.4 57.7 NS NS NS
1.25 1.38 1.27 1.54 1.32 1.76 1.33 1.84 p < 0.0001 p < 0.001 p < 0.05
1.27 1.11 1.22 1.16 1.22 1.15 1.24 1.15 p < 0.0001 NS NS
Abbreviation: BMI: body mass index; %FM: fat mass percentage; FM: fat mass; LM: lean mass; FMR: fat mass ratio; BMD: bone mineral density; NS: not significant.
Among treated HIV-infected men, as shown in Table 2, duration of treatment and FMR were significantly higher for those with clinical lipodystrophy than for those without clinical lipodystrophy (p < 0.05). Treated HIV-infected men with clinical lipodystrophy were patients with the most elevated mean FMR (1.9 ± 0.5), significantly above the threshold defining lipodystrophy by DXA. The BMD and BMI were identical for these two groups. Results of linear regression according to age, duration of HIV seropositivity, CDC stage, CD4 cell count, viral load, and duration of treatment for each antiretroviral compound are presented in Table 3, a higher FMR was observed for patients receiving zidovudine (AZT), stavudine (d4T), or indinavir (IDV). None of these variables was correlated with BMD in linear regression.
Discussion To our knowledge, this is the first study comparing HIV patients to such a large number of HIV-negative men using DXA. Our control group was comparable to the general French population according to height and weight (12). In our study, the mean BMD was 1.23 and remained stable through all age ranges, as shown previously in the European population by Karlson et al. (13). The control group was homogenous and exclusion criteria were rigorous according to those published by Mazess et al. for the definition of BMD norms (1,14). Thus, our control group can be considered as a valid population for reference. To our knowledge, this is also the first study proposing standard values for the FMR measured by DXA in order to define lipodystrophy. The FMR for HIV-treated patients with clinical lipodystrophy was very high and largely above the threshold value that defines lipodystrophy by DXA (FMR ≥ 1.5). Furthermore, the mean FMR for HIV-treated patients without clinical lipodystrophy was equal to this limit value. Thus, the diagnosis of lipodystrophy assessed by clinical exam seems to Journal of Clinical Densitometry
be delayed. In our study, if we made the hypothesis that DXA was the gold standard for diagnosis of lipodystrophy, clinical exam had a sensitivity of 67.5%, a specificity of 66%, a positive predictive value of 77%, and a negative predictive value of only 55%. To date, the use of the FMR should allow a more accurate diagnosis of lipodystrophy. The mean age and lean mass were similar for HIV patients and controls. Age is known as a key factor for lipodystrophy (6), but to our knowledge, no comparison of fat distribution between HIV-infected men and controls by age classes has been conducted. We observed an age effect on BMI and FMR for both control and HIV-infected men, as these two parameters were higher for older men. Therefore, the difference in BMI can be only explained by the fat mass variations. Our results were consistent in the whole population and for the four age groups. The FMR increases with age in both HIV patients and controls; however it is significantly and markedly higher in HIV patients In our HIV population, the FMR was not statistically associated with the CDC stage, duration of seropositivity, viral load, and CD4 cell count at the time of DXA. These results argue against a direct role of the evolution or the stage of HIV disease in lipodystrophy, as shown in one other study (15), but contrarily to others (16–18). Antiretroviral therapy has been identified as an important risk factor for lipodystrophy (8,15,19–21). Indeed, in our study, we confirmed that the FMR in naïve patients was similar to that measured in controls, although it was significantly higher for those under HAART than for those who have never been treated. Moreover, as shown in previous studies (20–22), we found the duration of treatment to be correlated with clinical lipodystrophy. As reported in previous studies, we found the following variables to be positively correlated with lipodystrophy index: age (4,23), cumulative time on d4T (9,23,24), or indinavir (10,11). The positive correlation with ZDV we also Volume 8, 2005
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32.48 (18.9) 27.74 (19.3) 36.41 (17.8)
176 (5) 175 (6) 175 (7) 175 (6) 175 (7)
42a,b,c (8) 174c (5)
39 (8) 39 (9) 35a (9) 40b (8) 38 (8) 22.9a (2.5)
25.4 (2.9) 23.3p (3.2) 23.2a (3.1) 23.3a (3.2) 23.8a (3.8)
Age (SD) Height (SD) Treatment duration (yr) (cm) (SD) (mo) BMI (SD)
12.9a (5)
20.4 (6) 13.8a (6) 14.2a (7) 13.6a (6) 14.6a (6)
%FM (SD)
bComparison
with controls; significative difference at a threshold inferior to 5%. with no treated HIV population; significative difference at a threshold inferior to 5%. cComparison with treated and not lipodystrophic HIV population; significative difference at a threshold inferior to 5%.
aComparison
Controls 241 HIV population 162 Naïve HIV population 34 Treated HIV population 128 Treated and not lipodystrophic 58 HIV population Treated and lipodystrophic 70 HIV population
n
57.9 (6.8)
59 (5.4) 58.3 (7.8) 57.8 (7.1) 58.5 (8) 59.2 (9.2)
LM (SD) (kg)
1.9a,b,c (0.5)
1.3 (0.2) 1.6a (0.5) 1.2 (0.2) 1.7a,b (0.5) 1.5a,b (0.5)
FMR (SD)
1.14a,b,c (0.07)
1.23 (0.08) 1.15a (0.08) 1.18a (0.10) 1.15a,b (0.08) 1.15a (0.08)
BMD (SD) (g/m2)
Table 2 Comparison of Anthropometric and DXA Variables Between Controls and HIV Patients, According to Presence of Treatment and Clinical Lipodystophy
Total Body Composition by DXA of 241 HIV-Negative Men and 162 HIV-Infected Men Table 3 Independent Variables Associated With FMR, With a Linear Regression Model
Constant Age ZDV D4T IDV
n
t-test
128 128 108 87 72
6 2.28 5.03 5.95 3.96
Partial r
p
0.18 0.37 0.43 0.30
<0.0001 <0.05 <0.001 <0.0001 <0.001
found is less often mentioned. It could be because stavudine seems to lead to an earlier onset of fat wasting than zidovudine (23). Duration on stavudine has also been identified as a risk factor (25). In our study, treated patients had a slightly lower BMD than naïve patients, which could imply an effect of antiretroviral drugs on loss of bone mineral mass. In one study, Knobel et al. found that only HIV infection and the duration of HIV infection were at-risk factors for osteopenia, but not treatment or duration of treatment (26). However, we presented a prospective 14 mo longitudinal study on bone mineral content comparing HIV-treated patients and controls in which only HIV-naive patients developed a significant bone loss no longer than 14 mo after initiation of HAART (27). These results are still controversial, as some studies emphasized the role of antiretroviral treatment (28,29) and others did not (30–33). Artifactual bone changes with weight loss or gain is reported in studies including obese subjects. Decrease of bone mineral content was associated with short-term weight loss, but these results have been found using densitometers other than Lunar DPX (34). Moreover, our populations did not involve obese subjects. Thus, as reported previously (3,35), we have shown that low bone mass is a concern in HIV individuals, in our four age groups.
Conclusion Dual-energy X-ray absorptiometry is an innocuous, reproducible, and precise device for evaluating the total-body composition and distribution, but no standard values have been published for French healthy men for body composition. We obtained measurements of BMD, total fat mass, fat mass percentage, and FMR from the largest series of HIVnegative men ever studied. Our population had a lower BMD and a higher FMR than controls. We considered the mean value for FMR in our control population as the standard value of fat mass distribution. The use of FMR should improve diagnosis of lipodystrophy. We showed that the rise of FMR, observed through age groups, was accelerated in HIV-treated men. Fat mass redistribution and bone loss are possible distinct adverse effects. Our data emphasize the need for longitudinal studies in order to identify fat and bone changes earlier and to monitor the progression of theses anomalies. The results of these studies could lead clinicians Journal of Clinical Densitometry
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to consider DXA for routine assessment of body composition and bone mass in HIV-infected men.
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Volume 8, 2005
Original Article
Total Body Composition by DXA of 241 HIV-Negative Men and 162 HIV-Infected Men Proposal of Reference Values for Defining Lipodystrophy E. Bonnet,*,1,2 C. Delpierre,6 A. Sommet,1 F. Marion-Latard,3 R. Hervé,1 C. Aquilina,5 E. Labau,1 M. Obadia,1 B. Marchou,1 P. Massip,1 B. Perret,2 and J. Bernard4 1Unit of Infectious and Tropical Disease and 2INSERM U 563, Purpan Hospital, Toulouse, France; 3Unit of Sport Medicine and 4Unit of Rhematology, Rangueil Hospital, Toulouse, France; 5Unit of Dermatology, La Grave Hospital, Toulouse, France; and 6Unit of Epidemiology and Public Health, INSERM U558, Toulouse, France
Abstract The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIVinfected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value ± standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3 ± 0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier. Key Words: HIV; lipodystrophy; DXA; fat mass ratio; antiretroviral drugs; bone mineral density.
Intorduction
antiretroviral treatment [HAART]) has been recognized as one of the major long-term adverse effect of antiretroviral combinations (2,3). Osteopenia is also one of the main concerns for HIV-infected people; however the specific role of HIVdisease-related factors and anti-HIV treatment per se has to be clarified (4). Large discrepancies in lipodystrophy incidence reported in previous studies are the result of the lack of homogeneous criteria for the diagnosis of lipodystrophy (5). Greater use of DXA and the determination of standard values for fat mass distribution could improve early detection and diagnosis of lipodystrophy. However, no standard values of body composition by DXA are available for HIV-negative men. We compared body composition as measured by DXA in a large cohort of HIV-negative men to a cohort of HIV-infected
Dual-energy X-ray absorptiometry (DXA) is a reliable technic for measuring total-body and regional bone mineral and soft tissue composition (1). Its usefulness for measuring fat redistribution in metabolic diseases has become increasingly evident. Since 1996 to 1997, lipodystrophy (which is notably different from acquired immunodeficiency syndrome [AIDS]wasting syndrome described in human immunodeficiency virus [HIV]-infected patients before the era of highly active Received 11/04/04; Revised 01/21/04; Accepted 02/02/05. *Address correspondance to: E. Bonnet, Hôpital Purpan, Place du Docteur Baylac, 31059 Toulouse cedex, France. E-mail: bonnet.e@ chu-toulouse.fr
287
288 men followed in one university hospital in southern France. We believe this to be the largest group of such HIV-negative, normal men reported to date. The aims of our study were to define standard values for body composition in HIV-negative men, to compare these values to those of HIV-infected men, and to analyze factors associated with low bone mass and lipodystrophy as measured by DXA in HIV-infected men.
Patients and Methods We conducted a cross-sectional analysis on 403 men (age: 20–60 yr). Two-hundred forty-one men were HIV-negative volunteers without any medical or surgical history, needing neither therapies nor immobilization longer than 2 mo, designed as controls. One-hundred sixty-two men were HIVinfected outpatients at steady state, naïve (34 patients), or treated (128 patients), with or without clinical lipodystrophy, without current opportunistic disease, and not under prophylactic regimen. The controls have been selected at the time of a routine medical visit for evaluating ability to work and they all agreed to participate to a study designed to define normal values of bone mineral density (BMD) in French men. Because DXA gives a reproducible and precise fat mass percentage of the trunk, limbs, and total body (6), we measured a lipodystrophy index defined by the ratio of the trunk fat mass percentage over the lower limbs fat mass percentage. We defined it as the fat mass ratio (FMR = % of the trunk fat mass/% of the lower limbs fat mass). The two main reasons why we chose this index were that 80% of trunk fat mass is perivisceral and 98% of limbs fat mass is subcutaneous (7) and that lipodystrophy in HIV-people might be the result of a loss of subcutaneous fat mass, an accumulation in perivisceral fat mass, or both (2,8–11). We attempted to determine standard values for FMR according to the mean value ± standard deviations measured for HIV-negative men. The threshold chosen for defining lipodystrophy by DXA corresponded to the value for FMR above the mean value ± standard deviation measured for HIVnegative men. Clinical lipodystrophy was defined as a peripheral lipoatrophy with or without a central fat accumulation assessed by both patient and practitioner. Total-body bone mineral and soft tissue composition were measured by DXA with DPX-L (Lunar Corporation®) acquisition and analysis software 4.6. Markers used in this study for trunk and lower limbs that defined regions of interest were those indicated by the manufacturer. All subjects gave written informed consent. We compared body mass index (BMI) indicated in medical record, fat mass percentage (%FM), lean mass (LM), total BMD, and FMR between the whole population of the two groups and by age range, between naïve and treated patients, and between treated patients with clinical lipodystrophy and treated patients without clinical lipodystrophy. In the HIV group, we studied correlation among age, duration of seropositivity, duration of antiretroviral drugs use, CDC stages, viral Journal of Clinical Densitometry
Bonnet et al. load (determined by the Amplicor Monitor Roche® test, limit of detection: 20 copies/mL), CD4 cell count, BMD, and FMR at the time of DXA.
Statistical Analysis Means and standard deviations were determined for all variables. We compared controls and HIV-infected men classified by age range using two-way analysis of variance (ANOVA) and subgroups (naïve HIV-infected men, treated HIV patients, with or without clinical lipodystrophy) using ANOVA, according to age. We used descending stepwise linear regression to correlate BMD and FMR (dependent variables) to age, duration of HIV seropositivity, CDC stage, CD4 cell count, viral load, and duration of treatment for each antiretroviral compound (independent variables) at the time of DXA.
Results Controls The mean age was 39 ± 8 yr, the mean height was 176 ± 5 cm, the mean BMI was 25.4 ± 2.9. The mean FMR was 1.3 ± 0.2. Thus, standard values for FMR in HIV-negative men were between 1.1 and 1.5. An age effect was found for FMR and BMI, as FMR and BMI were higher for older men (p < 0.001 and p < 0.01, respectively). The mean BMD was 1.23 ± 0.08.
HIV-Infected Men The mean age was 39 ± 9 yr, the mean height was 175 ± 6 cm, and the mean BMI was 23.3 ± 3.2. The mean duration of seropositivity was 69.2 ± 58 mo. The mean duration of treatment was 33 ± 18 mo. Clinical stages according to the CDC classification were A for 97 patients, and B for 40 patients, and C for 25 patients. The mean viral load was 2.6 ± 1.5 log-copies/mL, the mean CD4 cell count was 485 ± 250/mm3 (data not presented in tables). There was no statistical difference in FMR and BMD according to the CDC stage, duration of seropositivity, viral load, or CD4 cell count at the time of DXA (Tables 1 and 2). As shown in Tables 1 and 2, when compared to controls, HIV-infected men had a lower BMD (1.15 vs 1.23, respectively; p < 0.0001) and a higher FMR (1.6 vs 1.3, respectively, p < 0.0001). The mean FMR was above the threshold defining lipodystrophy by DXA for HIV men. As shown for controls, the FMR and BMI were higher in older patients (p < 0.001 and p < 0.01, respectively). HIV-infected men also exhibited a lower BMI (p < 0.0001) and a lower percent fat mass (p < 0.0001). The total LM was identical in the two groups. As shown in Table 2, under the threshold value defining lipodystrophy by DXA, naïve HIV-infected men and controls had a similar FMR. Naïve HIV-infected men had a lower BMD and BMI. Among HIV-infected men, the FMR was significantly higher for those receiving HAART than for those who have never been treated (p < 0.05) and above the threshold defining lipodystrophy by DXA. BMD was slightly lower in treated HIV-infected men (p < 0.05), and the BMI was identical. Volume 8, 2005
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Table 1 Comparison of Athropometric and DXA Varibles by Age Groups Between Controls and Patients n Controls 21 HIV 19 Controls 106 HIV 76 Controls 91 HIV 49 Controls 23 HIV 18 Population effect Age effect Interaction
Age class (yr)
Height (cm)
20–29 20–29 30–39 30–39 40–49 40–49 50–60 50–60
176 174 177 176 175 174 175 173 NS p < 0.05 NS
BMI 24.5 21.8 24.9 23.1 25.9 23.8 26.4 24.1 p < 0.0001 p < 0.01 NS
% FM 19 10 21 14 21 15 23 16 p < 0.0001 p < 0.01 NS
FM (kg) 15 6.6 16.1 10 16.8 11.1 18.5 11.5 p < 0.0001 p < 0.01 NS
LM (kg)
FMR
BMD (g/cm2)
58 56.7 58.7 58.8 59.3 58.5 59.4 57.7 NS NS NS
1.25 1.38 1.27 1.54 1.32 1.76 1.33 1.84 p < 0.0001 p < 0.001 p < 0.05
1.27 1.11 1.22 1.16 1.22 1.15 1.24 1.15 p < 0.0001 NS NS
Abbreviation: BMI: body mass index; %FM: fat mass percentage; FM: fat mass; LM: lean mass; FMR: fat mass ratio; BMD: bone mineral density; NS: not significant.
Among treated HIV-infected men, as shown in Table 2, duration of treatment and FMR were significantly higher for those with clinical lipodystrophy than for those without clinical lipodystrophy (p < 0.05). Treated HIV-infected men with clinical lipodystrophy were patients with the most elevated mean FMR (1.9 ± 0.5), significantly above the threshold defining lipodystrophy by DXA. The BMD and BMI were identical for these two groups. Results of linear regression according to age, duration of HIV seropositivity, CDC stage, CD4 cell count, viral load, and duration of treatment for each antiretroviral compound are presented in Table 3, a higher FMR was observed for patients receiving zidovudine (AZT), stavudine (d4T), or indinavir (IDV). None of these variables was correlated with BMD in linear regression.
Discussion To our knowledge, this is the first study comparing HIV patients to such a large number of HIV-negative men using DXA. Our control group was comparable to the general French population according to height and weight (12). In our study, the mean BMD was 1.23 and remained stable through all age ranges, as shown previously in the European population by Karlson et al. (13). The control group was homogenous and exclusion criteria were rigorous according to those published by Mazess et al. for the definition of BMD norms (1,14). Thus, our control group can be considered as a valid population for reference. To our knowledge, this is also the first study proposing standard values for the FMR measured by DXA in order to define lipodystrophy. The FMR for HIV-treated patients with clinical lipodystrophy was very high and largely above the threshold value that defines lipodystrophy by DXA (FMR ≥ 1.5). Furthermore, the mean FMR for HIV-treated patients without clinical lipodystrophy was equal to this limit value. Thus, the diagnosis of lipodystrophy assessed by clinical exam seems to Journal of Clinical Densitometry
be delayed. In our study, if we made the hypothesis that DXA was the gold standard for diagnosis of lipodystrophy, clinical exam had a sensitivity of 67.5%, a specificity of 66%, a positive predictive value of 77%, and a negative predictive value of only 55%. To date, the use of the FMR should allow a more accurate diagnosis of lipodystrophy. The mean age and lean mass were similar for HIV patients and controls. Age is known as a key factor for lipodystrophy (6), but to our knowledge, no comparison of fat distribution between HIV-infected men and controls by age classes has been conducted. We observed an age effect on BMI and FMR for both control and HIV-infected men, as these two parameters were higher for older men. Therefore, the difference in BMI can be only explained by the fat mass variations. Our results were consistent in the whole population and for the four age groups. The FMR increases with age in both HIV patients and controls; however it is significantly and markedly higher in HIV patients In our HIV population, the FMR was not statistically associated with the CDC stage, duration of seropositivity, viral load, and CD4 cell count at the time of DXA. These results argue against a direct role of the evolution or the stage of HIV disease in lipodystrophy, as shown in one other study (15), but contrarily to others (16–18). Antiretroviral therapy has been identified as an important risk factor for lipodystrophy (8,15,19–21). Indeed, in our study, we confirmed that the FMR in naïve patients was similar to that measured in controls, although it was significantly higher for those under HAART than for those who have never been treated. Moreover, as shown in previous studies (20–22), we found the duration of treatment to be correlated with clinical lipodystrophy. As reported in previous studies, we found the following variables to be positively correlated with lipodystrophy index: age (4,23), cumulative time on d4T (9,23,24), or indinavir (10,11). The positive correlation with ZDV we also Volume 8, 2005
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32.48 (18.9) 27.74 (19.3) 36.41 (17.8)
176 (5) 175 (6) 175 (7) 175 (6) 175 (7)
42a,b,c (8) 174c (5)
39 (8) 39 (9) 35a (9) 40b (8) 38 (8) 22.9a (2.5)
25.4 (2.9) 23.3p (3.2) 23.2a (3.1) 23.3a (3.2) 23.8a (3.8)
Age (SD) Height (SD) Treatment duration (yr) (cm) (SD) (mo) BMI (SD)
12.9a (5)
20.4 (6) 13.8a (6) 14.2a (7) 13.6a (6) 14.6a (6)
%FM (SD)
bComparison
with controls; significative difference at a threshold inferior to 5%. with no treated HIV population; significative difference at a threshold inferior to 5%. cComparison with treated and not lipodystrophic HIV population; significative difference at a threshold inferior to 5%.
aComparison
Controls 241 HIV population 162 Naïve HIV population 34 Treated HIV population 128 Treated and not lipodystrophic 58 HIV population Treated and lipodystrophic 70 HIV population
n
57.9 (6.8)
59 (5.4) 58.3 (7.8) 57.8 (7.1) 58.5 (8) 59.2 (9.2)
LM (SD) (kg)
1.9a,b,c (0.5)
1.3 (0.2) 1.6a (0.5) 1.2 (0.2) 1.7a,b (0.5) 1.5a,b (0.5)
FMR (SD)
1.14a,b,c (0.07)
1.23 (0.08) 1.15a (0.08) 1.18a (0.10) 1.15a,b (0.08) 1.15a (0.08)
BMD (SD) (g/m2)
Table 2 Comparison of Anthropometric and DXA Variables Between Controls and HIV Patients, According to Presence of Treatment and Clinical Lipodystophy
Total Body Composition by DXA of 241 HIV-Negative Men and 162 HIV-Infected Men Table 3 Independent Variables Associated With FMR, With a Linear Regression Model
Constant Age ZDV D4T IDV
n
t-test
128 128 108 87 72
6 2.28 5.03 5.95 3.96
Partial r
p
0.18 0.37 0.43 0.30
<0.0001 <0.05 <0.001 <0.0001 <0.001
found is less often mentioned. It could be because stavudine seems to lead to an earlier onset of fat wasting than zidovudine (23). Duration on stavudine has also been identified as a risk factor (25). In our study, treated patients had a slightly lower BMD than naïve patients, which could imply an effect of antiretroviral drugs on loss of bone mineral mass. In one study, Knobel et al. found that only HIV infection and the duration of HIV infection were at-risk factors for osteopenia, but not treatment or duration of treatment (26). However, we presented a prospective 14 mo longitudinal study on bone mineral content comparing HIV-treated patients and controls in which only HIV-naive patients developed a significant bone loss no longer than 14 mo after initiation of HAART (27). These results are still controversial, as some studies emphasized the role of antiretroviral treatment (28,29) and others did not (30–33). Artifactual bone changes with weight loss or gain is reported in studies including obese subjects. Decrease of bone mineral content was associated with short-term weight loss, but these results have been found using densitometers other than Lunar DPX (34). Moreover, our populations did not involve obese subjects. Thus, as reported previously (3,35), we have shown that low bone mass is a concern in HIV individuals, in our four age groups.
Conclusion Dual-energy X-ray absorptiometry is an innocuous, reproducible, and precise device for evaluating the total-body composition and distribution, but no standard values have been published for French healthy men for body composition. We obtained measurements of BMD, total fat mass, fat mass percentage, and FMR from the largest series of HIVnegative men ever studied. Our population had a lower BMD and a higher FMR than controls. We considered the mean value for FMR in our control population as the standard value of fat mass distribution. The use of FMR should improve diagnosis of lipodystrophy. We showed that the rise of FMR, observed through age groups, was accelerated in HIV-treated men. Fat mass redistribution and bone loss are possible distinct adverse effects. Our data emphasize the need for longitudinal studies in order to identify fat and bone changes earlier and to monitor the progression of theses anomalies. The results of these studies could lead clinicians Journal of Clinical Densitometry
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to consider DXA for routine assessment of body composition and bone mass in HIV-infected men.
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