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384 HIV+ Men found to have Body Abnormalities Compared to 314 HIV- Men
  "Anthropometrics and Examiner-Reported Body Habitus Abnormalities in the Multicenter AIDS Cohort Study"
Clinical Infectious Diseases 2004;38:903-907
Frank J. Palella, Jr.,1 Stephen R. Cole,2 Joan S. Chmiel,1 Sharon A. Riddler,4 Barbara Visscher,5 Adrian Dobs,2 and Carolyn Williams3,a
1Northwestern University, Chicago, Illinois; 2Johns Hopkins University, Baltimore, and 3National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland; 4University of Pittsburgh, Pennsylvania; and 5University of California, Los Angeles
--HIV+ men on HAART, compared to HIV- men, had lower weight (187 lbs vs 187), smaller waist (96 cm vs 90 cm), smaller hip (101 cm vs 95 cm), smaller arm 33 cm vs 32 cm), smaller thigh (54 cm vs 50 cm)--cm means centimeter; less HIV+ men & HIV+ men on HAART than HIV- men had BMI >30;
--moderate/severe face abnormality: more men on HAART (24%) had mod/severe face abnormality than HIV- men (1%);
--arm abnormality, mod/severe: 16% men on HAART vs 1% HIV- men;
--leg abnormality, mod/severe: 21% for men on HAART vs 1% for HIV- men
--buttocks, mod/severe abnormality: 20% for men on HAART vs 1% for HIV- men
--abdomen abnormality, mod/severe: 28% for men on HAART vs 16% for HIV- men
--dorsocervial pad, mod/severe abnormality: 5% for HIV+men vs<1% forHIV- men
--breast, mod/severe abnormality: no significant differences but possible slight increase for men on HAART
Several studies show HCV/HIV coinfected persons have greater risk for body changes & metabolic abnormalities than HIV-infected individuals. Weight loss and diabetes or glucose abnormalities can become exacerbated after starting interferon/ribavirin therapy so call for close monitoring.
ABSTRACT: We undertook anthropometric assessments of 530 HIV-seropositive and 314 HIV-seronegative men in the Multicenter AIDS Cohort Study at a regular visit that occurred between 1 April and 30 September 1999. We found anthropomorphic differences that were independent of age: the 384 seropositive men receiving HAART had diminished body size and higher frequency and severity of body habitus abnormalities, particularly lipoatrophy, compared with the 314 seronegative men.
Results. The 384 HIV-seropositive men receiving HAART (mean CD4+ counts of 505 cells/mL and mean log10 HIV-1 RNA of 3.0 log10 copies/mL) had lower body weight and smaller waist, hip, upper arm, thigh, and body mass index compared with the 314 HIV-seronegative men.
The HIV-seropositive men receiving non-HAART ART typically monotherapy or dual therapy with NRTIs frequently had body habitus measurements (e.g., weight) that were intermediate between those of the HIV-seropositive HAART recipients and the seronegative men. However, body habitus measurements for the general US population (from NHANES III) were variably similar to those for HIV-seronegative men (specifically, waist measurements), untreated seropositive patients (specifically, hip, arm, and BMI measurements), and non-HAART ART recipients (specifically, thigh and waist : hip ratio) in MACS. Seventy-three percent of men (57 of 78) classified in the "no ART" group had never received ART.
The 384 HIV-seropositive men receiving HAART demonstrated a markedly higher frequency and severity of body habitus abnormalities compared with the 314 HIV-seronegative men, excepting the occurrence of moon facies and abnormalities in breast size (table 1). The proportion of men with abnormalities at body sites other than the abdomen and breast appeared to rise in a graded fashion with the presence of HIV and exposure to ART. Lipoatrophy was rare (incidence, <2%) among HIV-seronegative men. In contrast, the incidences of abdominal and breast lipoaccumulation among HIV-seronegative men were 26% and 8%, respectively, with the latter value not markedly different from the noted incidence of breast lipoaccumulation among HIV-seropositive men receiving HAART (12%). As can be deduced from table 1, it was observed that HIV-infection and receipt of HAART had a stronger positive association with lipoatrophy (i.e., in the face, arms, legs, and buttocks) than it did with lipoaccumulation (i.e., in the abdomen, dorsocervical fat pad, and breast area).
TABLE 1. Anthropometrics and examiner-reported body habitus abnormalities by HIV status and therapy status for 844 men.
III n=314 n=530
N=78 n=62 n=384 p(b)
Age yrs 49 46 46 46 <.01
White race 85% 76% 76% 85% .92
Weight lbs 172 187 176 172 174 <.01
Height in. 68 70 69 69 70 .63
Body circumfrance cm
Waist 95 96 91 91 90 <.01
Hip 98 101 97 94 95 <.01
Arm 32 33 32 32 32 <.01
Thigh 51 54 52 51 50 <.01
Waist:hip ratio 0.96 0.95 0.93 0.96 0.95 .32
Mean ± SD 26 27 26 25 25 <.01
Low <18.5 <1% 0 0 <1%
High >30 22% 13% 13% 8% <.01
Body habitus abnormality
Face <.01
None 97% 88% 73% 58%
Mild 2% 9% 15% 18%
Moderate/severe 1% 3% 13% 24%
Arm <.01
None 98% 92% 76% 71%
Mild 1% 5% 16% 13%
Mod/severe 1% 3% 8% 16%
Leg <.01
None 99% 91% 69% 66%
Mild 1% 6% 21% 13%
Mod/severe 1% 3% 10% 21%
Buttocks <.01
None 98% 90% 71% 64%
Mild 1% 8% 19% 16%
Mod/severe 1% 2% 10% 20%
Moon facies .10
None 99% 100% 96% 98%
Mild <1% 0 2% 1%
Mod/severe 0 0 2% 1%
Abdomen <.01
None 74% 81% 63% 58%
Mild 10% 10% 5% 14%
Mod/severe 16% 9% 32% 28%
Dorsocervical fat pad <.01
None 95% 96% 92% 88%
Mild 5% 4% 3% 7%
Mod/severe <1% 0 5% 5%
Breast .16
None 92% 96% 86% 88%
Mild 3% 1% 6% 6%
Mod/severe 5% 3% 8% 6%

NOTE. Data are mean ± SD or n (%); because of rounding, percentages may not total 100. In., inches; lbs., pounds.
a Treatment classification was missing for 6 HIV-positive men.
b P value from age-standardized Wilcoxon or Fisher's exact tests comparing 384 HIV-positive men receiving HAART with 314 HIV-negative men.
c For definitions of categories, see Methods.

Discussion. Recent work has sought to evaluate anthropomorphic alterations that occur in HIV-infected, HAART-treated persons in comparison with age-matched and sex-matched control subjects. Such inquiry has been fueled by the interest in discerning between those body habitus and other metabolic alterations that may be consequent to aging, particularly in men, and those that may be more closely linked to advancing HIV infection and/or antiretroviral therapy. Our findings, although not longitudinal, support the idea that age-independent anthropomorphic differences exist between HIV-seropositive, HAART-treated men and HIV-seronegative men. Specifically, our examiner-reported findings demonstrated that (1) body habitus abnormalities discerned on physical examination were more common overall among HIV-seropositive, HAART-treated men than among HIV-seronegative men in our cohort, and (2) peripheral lipoatrophy was more common and more severe among HIV-seropositive, HAART-treated men than than among HIV-seronegative men. Note that, although abdominal adiposity was the most often reported form of lipoaccumulation (irrespective of HIV serostatus), the percentage of HAART-treated, HIV-seropositive men with examiner-reported abnormalities was not substantially greater than the percentage of HIV-seronegative men.
Although our intent was to describe and evaluate significant body habitus abnormalities, we acknowledge important limitations in our approach. Principal among these is that we present only cross-sectional data, whereas future and other ongoing work will necessarily involve longitudinal assessments. Further, our measurements are subject to variability because of the necessity of having >1 physical examiner at each of several study sites. Finally, since there were a relatively small number of men exposed to each of numerous possible ART combination regimens, precise exploration of ART drugspecific or ART regimenspecific associations with body habitus changes was not possible. Despite such limitations, these data have important implications. First, the high percentage of HIV-seronegative men with notable central fat accumulation suggests that peripheral fat loss may be more a distinguishing feature of HIV-associated lipodystrophy syndrome than is central fat gain. Also, these data indicate that isolated truncal lipohypertrophy is insufficient to diagnose HIV-related or HAART-related lipodystrophy syndrome. Further, these data once again underscore the importance of inclusion of HIV-seronegative individuals with "normal" age-related body habitus alterations as a concurrent comparison group. Last, these findings are consonant with other emerging work suggesting that factors other than HAART (e.g., patient age, race, gender, and stage of HIV disease) may be associated with the likelihood of developing anthropomorphic and metabolic abnormalities.
Widespread use of HAART since 1996 has resulted in marked and durable declines in HIV-associated mortality and morbidity, with consequent improvements in quality of life. Potent viral suppression and CD4+ cell count repletion achieved in HAART-treated persons has resulted in an extension of AIDS-free survival time, as well as increased survival time following the onset of clinical AIDS.
Within 2 years after the introduction of HAART, reports of diverse metabolic and body habitus abnormalities among HAART recipients began to emerge. These metabolic and body habitus abnormalities included elevations in serum lipid and glucose levels, as well as body sitespecific lipoaccumulation and lipoatrophy. Collectively, these findings have been called "lipodystrophy syndrome." Indeed, much investigative energy has been expended to establish a standard case definition that could (1) accommodate all the identified, and variably expressed, clinical components, (2) link observed abnormalities to one another or to shared pathophysiologic mechanisms, and (3) establish the strength and nature of associations between the abnormalities noted and specific antiretroviral therapy received.
Long-term comparisons of body habitus and other metabolic alterations in HIV-infected and uninfected persons over time are only now beginning to be done. Such studies seek, in part, to evaluate possible increased cardiovascular risk consequent to HIV-associated lipodystrophy syndrome. Herein we report on anthropometrics and examiner-reported body habitus abnormalities in a cross-sectional analysis of 844 men.
Methods. The Multicenter AIDS Cohort Study (MACS), with sites in Baltimore, Chicago, Los Angeles, and Pittsburgh, is a prospective study of the natural history of HIV disease that began in 1984 and enrolled 5622 men by 1991.
At their 31st MACS visit, which occurred between 1 April and 30 September 1999, a total of 869 men completed a detailed interview and underwent a physical examination that included both anthropometric measurements (height; weight; and upper arm, thigh, waist, and hip circumferences) obtained using a standardized protocol based on the Third National Health and Nutrition Examination Survey (NHANES III) and examiner-reported body habitus alterations.
Training for examiners included review of written guidelines and use of a NHANES instructional videotape. Examiners assessed fat loss in the upper arms, legs, buttocks, and face, as well as fat accumulation in the abdomen, breast, and back of neck, and the presence of moon facies. Body habitus alterations were scored as "none," "mild," "moderate" or "severe." Mild signs were defined as those noticeable only upon close inspection, moderate signs as those noticeable upon inspection, and severe signs as those easily noted upon casual observation. Height and weight were measured to the nearest inch and pound using a clinical stadiometer and balance scale, respectively. Waist and hip circumferences were recorded to the nearest centimeter, and arm and thigh girths were recorded to the nearest millimeter by tape measure.
Results were restricted to the 844 (of 869) men for whom the examiner reports had complete data. CD4+ cell counts were determined by flow cytometry at National Institute of Allergy and Infectious Diseases (NIAID) Flow Cytometry Quality Assessment Programcertified laboratories. Plasma HIV-1 RNA titers were determined by the isothermal nucleic acid sequencebased amplification method in National Institutes of Health (NIH) Virology Quality Assurancecertified laboratories, with a lower limit of detection of 50 copies/mL. Institutional review boards of participating institutions approved study protocols and forms, and participants provided written informed consent. In addition to the MACS data on HIV-seropositive and HIV-seronegative men, we provide summary anthropometric measurements for adult male participants from NHANES III for comparison with the general US population.
HIV-seropositive men were classified, on the basis of antiretroviral therapy (ART) received during the prior 6 months, into 3 groups: no ART, ART monotherapy and combination therapy, and HAART. HAART was defined according to the US Department of Health and Human Services/Kaiser Panel guidelines, as follows: (1) 2 nucleoside or nucleotide reverse-transcriptase inhibitors (NRTIs) in combination with at least 1 protease inhibitor (PI) or 1 nonnucleoside reverse-transcriptase inhibitor (NNRTI); (2) 1 NRTI in combination with at least 1 PI and at least 1 NNRTI; (3) a regimen including ritonavir and saquinavir in combination with 1 NRTI and no NNRTIs; and (4) a regimen of 3 NRTIs, including abacavirand no PIs or NNRTIs. Combinations of zidovudine and stavudine with either a single PI or a NNRTI were not considered HAART. Age-standardized Wilcoxon tests for the difference in distributions or Fisher's exact tests for the difference in proportions were used for comparison of therapy subgroups, as appropriate.
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