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Yeweyenhareg Feleke, Daniel Fekade, Yared Mezegebu, 2012. Ethiop Med J, Vol. 50, No. 3
ORIGINAL ARTICLE
PREVALENCE OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ASSOCIATED
METABOLIC ABNORMALITIES AND LIPODYSTROPHY
IN HIV INFECTED PATIENTS
Yeweyenhareg Feleke*, MD, CSIM, MPhil 1 , Daniel Fekade, MD, CSIM, MSc 2 , Yared Mezegebu, MD 3
ABSTRACT
Background: Highly active antiretroviral therapy (HAART) improves the longevity of HIV patients. However, the
side effect of the drugs leads to development of chronic metabolic and cardiovascular complications.
Objective: The aim of the study was to detemine the prevalence and risk factors of the metabolic abnormalities
and lipodystrophy among adult Ethiopian HIV infected patients on ART for one year and above.
Methods: A cross-sectional study was conducted among HIV infected patients on HAART for one year or more,
attending the ART clinics of Tikur Anbessa Specialized hospital in Addis Ababa. A total of consecutive 356 HIV
infected patients volunteered to participate in the study from July 2007 to January 2008. Data was collected using
clinical interview technique on structured questionnaires and physical examination of the patient, 319 had biochemical
tests performed.
Results: Three hundred fifty six HIV patients; 261 (73.1%) females and 95 (26%) males were studied. Two hundred
nine (59.7%) patients were on Stavudine based and 135 (41.3%) were on Zidovudine based ART therapy. The
overall prevalence of lipodystrophy was 68.3% (243), prevalence of hyperlipademia among 319 HIV patient was
56.9%. Among these, the prevalence of hypercholesterolemia was 38.2 %, high LDL cholesterol was 54.2%, hypertryglyceredimeia
was 15.2%. Fasting hyperglycemia was 17.8 %, (IFG in 10.9% and overt diabetes in 6.9%). History
of smoking was significantly associated with lipoatrophy and lipohypertrophy. ART regimen d4T was significantly
associated with lipoatrophy. Duration of ART treatment >1yr was significantly associated with both lipoatrophy,
lipohypertrophy and hypertriglyceredemia.
Conclusions and Recommendations: Lipodystrophies occurred in majority of patients on ART treatment for
longer than one year, hyperlipaedemia and hyperglycaemia were also seen commonly in Ethiopian HIV patients
on HAART. We recommend careful monitoring of metabolic abnormalities, examination of the patient for early
detection of the side effect, change of the offending agents management of metabolic abnormalities.
Key words; diabetes mellitus , HAART, HIV, hyperlipaedemia, Impaired Fasting Glucose, Lipodystrophies, Metabolic
abnormalities.
INTRODUCTION
Highly Active Antiretroviral Therapy (HAART) is
known to cause a metabolic syndrome consisting of
morphologic and metabolic abnormalities. The morphologic
manifestations consist of the development
of lipoatrophy and/or lipohypertrophy, and the metabolic
abnormalities include insulin resistance, hyperinsulinemia,
hyperglycemia, hyperlipidemia (1, 2, 3).
It has been suggested that protease inhibitors (PI)
induced peripheral cellular lipolysis plays a key role
in the development of lipodystrophy. Moreover, nucleoside
reverse transcriptase inhibitors (NRTI) induced
mitochondria toxicity may further explain the
wasting and accumulation of body fat (4, 5).
Exact prevalence and incidence of HIV /HAART
associated lipodystrophy is not known, because of
lack of standard definition, difficulties in measurement
and wide variations in assessment (6). Many
*
Corresponding author 1 Endocrinology and Metabolism Unit, Department of Internal Medicine, School of Medicine, College of Health Sciences,
Addis Ababa University, yeweyenharegf@yahoo.com Addis Ababa, Ethiopia
2
Division of Infectious Disease, Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University,
Addis Ababa, Ethiopia
3
Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia

222
studies have attempted to establish the prevalence of
HIV associated lipodystrohy, which has been estimated
to be between 2 to 84 % in patients who were
on Protease Inhibitor containing HAART regimens
(1, 7, 8). Lipoatophy is linked to antiretroviral treatment
(ART) and in particular stavudine (d4T) and in
a lesser degree zidovudine (AZT) and didanosine
(ddl ) (9). Based on findings of epidemiological studies,
the syndrome is thought to develop after 10-18
months of HAART (8). The etiology of these metabolic
abnormalities remains unknown, although it
appears to be multifactorial in origin and there are
many identified risk factors: including PI, NRTI
and NNRTI treatment, age, gender, duration and
severity of HIV disease, viral load, duration of ART,
and body mass index (10, 11,12 ).
Diabetes is much more prevalent in HIV subjects
with lipodystrophy than in those without it (13, 14).
A study has shown that the rate of incident of diabetes
was 4.7 cases per 100 people- years among HIV
infected men compared with 1.4 cases per 100 person’s
year among HIV seronegative men (15). Metabolic
abnormalities commonly seen in the lipodystrophy
syndrome include hyperinsulinemia, insulin resistance,
hyperglycemia, hypertriglyceridemia and
hypercholesterolemia (16, 17).
In Ethiopia, fee based ART program was officially
launched by the government in July 2003. In 2005,
Ethiopia launched free ART program, over 246,347
were initiated on ART by the end of February 2010
and about 532 treatment sites are now providing
HIV care and treatment services in all regions (18,
19). So far, to the best of author (s) knowledge, no
published data are available to evaluate the magnitude
of metabolic abnormalities and lipodystrophy in
HIV patients in Ethiopia.
The aim of the study was to determine the prevalence
and risk factors of the metabolic abnormalities and
lipodystrophy among adult Ethiopian HIV infected
patients who had been on ART for at least one year
and more.
PATIENTS AND METHODS
The study design was cross-sectional among HIV
infected adult patients on HAART. The reference
populations were all HIV patients coming to ART
clinics of Tikur Anbessa Specialized University Hospital.
The Tikur Anbessa Specialized hospital
launched free ART treatment in March 2005. Until
the study period, a total of 3,710 HIV patients were
registered. Among these 2,361 patients were started
on ART. Those HIV patients with history of hyperlipaedemia,
hypertension and diabetes mellitus before
the initiation of HAART, patients on HAART
less than one year, age less than 18 years, critically
ill patients and non- volunteers were excluded from
the study.
The target populations were patients who had taken
HAART for one year or more and attending the ART
clinics of Tikur Anbessa Specialized Hospital. Sample
size determination was based on the formula with
single population proportion (N=Z2α/2P (1-p) /D).
The margin of error of 0.05, Confidence level of 1.96
and prevalence of side effects varying from 5-50% to
get the maximum sample size. Thus the sample size
calculated to be 384. Consecutively 356 HIV patients
volunteered to participate in the study were included.
The study was conducted from July 2007 to January
2008.
The data was collected by a physician and ART
trained nurses after adequate training on data collection
and interpretation of clinical findings. Data was
collected using clinical interview, structured questionnaires,
and physical examination of the patient.
Five milliliter of blood was used for determination
blood lipid profiles for total cholesterol, low density
lipoprotein (LDL) cholesterol, high density lipoprotein
(HDL) cholesterol, triglycerides and fasting glucose
level.
The analysis performed by senior laboratory technologist
in research laboratory of Endocrinology and
metabolism Unit using Photometer 5010, Semi- automated
single beam filter photometer, Robert Rifel
KG, Berlin, Germany. We applied an end point colorimetric
method and developed LG chart and West
gard rules for quality assessment.
In addition, data Quality was assured by training of
nurses who have ample experience on ART management,
preparing structured questionnaires and supervision
of the research activities by the senior collaborators
of the project. The following standard definitions
were used in the current study.
HAART related Lipoatrophy was mean when subcutaneous
fat depletion and wasting most commonly
around the face especially the cheeks below the zygomas,
the extremities, and gluteal regions, veins
appears more prominent in fat depleted regions
(8,10,16). HAART related Lipohypertrophy was

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mean when truncal obesity (central fat accumulation
evidenced by increased waist circumference, in females
>88 cms and males >102 cms), presence of
dorsocervical fat accumulation (buffalo Hump) and
breast enlargement in female and gynecomastia in
male was also be taken as indicators of lipohypertrophy
(8,10,16). Hypertension was considered when
blood pressure was > 140/90 mm/Hg.
Hyperlipidemias was defined in the presence of one
of the following: Total cholesterol > 200 mg/dl, HDL
< 35 mg/dl, or LDL Cholesterol values >150 mg/dl,
Serum Triglyceride levels > 150mg/dl. Hyperglycemia
was defined when Fasting plasma Glucose Levels
was >100 mg/dl. Impaired Fasting Glucose (IFG)
means when fasting plasma Glucose is between 100
-125 mg/dl, Diabetes mellitus was defined when
Fasting plasma Glucose Levels was 126 mg/dl or
more (20 ).
Data was entered into the computer and analyzed
using SPSS. 15.0 version. Descriptive analysis was
done; chi square tests and regressions used to assess
the associations of variables. The Ethical clearance
of the research was obtained from the Research and
Publication Committee (FRPC), Faculty of Medicine
of Addis Ababa University. The study participants
were informed about the risk and benefits of the
study; the right to withdraw from the study and no
impact on their treatment and care if they refuse to
take part in the study. Written informed consent was
obtained from all participants. Data collection, analysis
and write up were kept confidential. Those patients
identified with metabolic abnormalities were
referred to physicians and diabetic clinic of the hospital
for follow up and management.
RESULTS
A total of 356 patients were included in to the study;
among them 319 had complete biochemical studies.
As shown in Table 1: 261 (73.1%) were females and
95 (26%) were males; the mean age for females was
34.5 + 7.65 (range: 20-60 years) and for males 40.24
+ 9.22 (range:18-65). Eighty one percent of the study
participants were in stage III and Stage IV HIV diseases
(58.8% and 22.9 %, respectively). One hundred
twenty eight (39.9%) patients had been on HAART
for 12-18 months, 81 (25.2%) from 19-24 months
and 112 (34.9%) more than 24 months. The overall
prevalence of lipodystrophy in 356 patients was
68.3% (243). The prevalence of lipoatrophy was
57.3% (204). The prevalence of lipohypertophy was
46.3% (165), among this buffalo hump occurred in
78 (22%) of patients.
Table 1: Baseline Characteristics of 356 HIV patients
on HAART for one year and above, at ART clinics
of Tikur Anbessa Specialized Hospital, July 2007 to
January 2008.
Variables Number Frequency
(% )
Sex
Male 95 26.7
Female 261 73.1
Martial Status
Single 96 27
Married 153 43.1
Divorced 54 15.2
Widowed 52 14.6
Ethnics group
Amhara 194 54.6
Oromo 76 21.4
Tigrian 41 11.5
Gurage 41 11.5
Others 3 0.8
Duration of HAART
treatment
12 -18 months 128 39.9
19 -24 months 81 25.2
> 24 months 112 34.9
WHO HIV staging
Stage I 7 2.0
Stage II 58 16.4
Stage III 208 58.8
Stage IV 81 22.9
Lipodystrophy 243 68.3
Lipoatrophy* 204 57.3
Face 116 32.6
Extremities 184 51.7
Buttock 63 17.4
Prominent superficial 85 23.9
veins and muscules
Lipohypertrophy* 165 46.3
Dorso cervical 78 21.9
Breast enlargement 66 18.5
Fat accumulation
around the abdomen
146 41.0

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As shown in Table 2, the mean waist circumference
of the 356 study participant was 67.9 + 24.45; and
hip circumference was 71.43 + 25.64. Among the
patients on HAART for a year and above 51 of female
participants had increased waist circumference
above 88 cms compared to 4 male patients who had
increased waist circumference above 102 cms.
Among possible risk factors for metabolic abnormalities
in HIV patients on HAART treatment, 24
(6.2%) of them had family history of diabetes, 10
(2.8%) had family history of hypertension, only 3
had family history of cardiac diseases (Table 3).
Table 2: Anthropometric and Blood pressure measurement of 356 HIV patients on HAART for one year and
above, at ART clinics of Tikur Anbessa Specialized Hospital, July 2007 to January 2008.
Variables
Number Mean + SD Minimum- maximum
(Frequency
%)
Height
Male 95 168.46 (10.18) 110 - 192
Female 261 153.60 (7.48) 105-186
Weight
Male 95 63.05 ( 12.83) 38-112
Female 261 56.04 (9.71) 32 -102
BMI
Male 95 22.1(6.3)
Female 261 23.2(5.2)
Waist Circumference
(WC) cms
67.9 (24.45) 27 -131
Male – 102 4 (4.3) - -
Female < 88 cms 205 (80.1) - -
>88 cms 51 ( 19.9) - -
Hip Circumference ( HP) 71.43 (25.64) 27-123
Male
Female
Blood pressure
Systolic 356 112.01 (19.73) 40-200
Diastolic 356 71.42 (14.30) 50-120

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Table 3: Risk Factors for metabolic abnormalities in 356 HIV Patients on HAART for one year and above,
at ART clinics of Tikur Anbessa Specialized Hospital, July 2007 to January 2008.
Risk factors Number Frequency
(% )
History of alcohol consumption 8 23
History of Smoking 24 6.8
Family hx of DM 24 6.2
Family hx of HTN 10 2.8
Family hx of cardiac illness 3 0.8
Type of HAART treatment
1. d4T (30)/3TC/NVP 118 33.1
2. d4T (40)/ 3TC/NVP 38 10.7
3. d4T (30)/3TC/EFV 49 13.8
4. d4T (40)/3TC/EFV 16 4.5
5 . ZDV/3TC/NVP 86 24.2
6. ZDV/3TC/EFV 49 13.8
Initial CD4 count
< 100 187 53
100- 200 151 42
.> 200 15 4.2
CD4 count during study period (> 1 yr. on
HAART)
< 100 16 4.8
100 - 200 90 27.1
> 200 226 68.1
One hundred eighteen (33%) of 351 patients were on
Stavudine-Lamuvidine-Nevarapine regimen, 86
(24%) of 351 patients were on Zidovudine - Lamuvidine
- Nevarapine regimen, 49 (13.8%) were on
Zidovudine- Lamuvidine -Effavirenz. Only 16 patients
were on Stavudine -Lamuvidine -Effavirenz
regimen. Overall 209(58.7 %) of them were on stavudine
based and135 (41.3 %) of them were on zidovudine
based treatment. Among the total patients
51 (14.35%) of them had history of change of medications
to other regimens.
As shown in Table 4, the overall prevalence of Hyperlipademia
in 319 HIV patients on HAART was
56.9%. Among these the prevalence of hypercholesterolemia
was 38.2 % , Hypertryglyceredimeia was
15.2%, Low HDL cholesterol was 42.3%, high LDL
cholesterol was 54.2%. Prevalence of Impaired Fasting
Glucose (IFG) was 10.9% and diabetes mellitus
was 6.9%. Overall the prevalence of hyperglycemia
in HARRT treated HIV patients was 17.8 %.

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Table 4 : Frequency and Mean of Biochemical and Metabolic tests in 319 HIV patients on HAART for
one year and above, at ART clinics of Tikur Anbessa Specialized Hospital, July 2007 to January 2008.
Variables Number % Mean + SD (Range)
Cholesterol (mg/dl) 189.52 + 61.98 (40- 811)
< 200 197 61.8
> 200 122 38.2
Triglycerides
178.35 + 109.77 (34-850)
(mg/dl)
< 150 270 84.6
> 150 49 15.4
HDL (mg/dl) 44.42 +17.50 (18 – 181)
< 40 40 42.3
> 40 184 57.7
LDL 108 .48 + 49..31 (25 -576)
< 150 146 45.8
> 150 173 54.2
FBS mg/dl 93.68 + 43.98 (51 -417)
< 100 263 82.2
100- 125 35 10.9
> 126 22 6.9
BUN (mg/dl) 319 26.07 (13.82), 10.142
Creatinine (mg/dl) 319 0.74 ((0.65), 0.1 -7
SGOT 319 29.37 (13.8), 8 -103
SGPT 319 28.08 (13.4), 8- 95
Alkaline phosphatase
319 193 .76 (103 .11), 19- 1200
As shown in Tables 5a and Table 5b, sex of the patient
was significantly associated with LDL cholesterol
(P = 0.002) and lipohypertrohy (P = 0.0001) but
showed no association with the others metabolic abnormalities.
History of smoking is significantly associated
with lipoatrophy (P=0.04) and lipohypertrophy
(P=0.05). ART regimen is significantly associated
with lipoatrophy (P = 0.03).
Duration of ART regimen was significantly associated
with both lipoatrophy (P=0.01), lipohypertrophy
(P=0.03), and hypertriglyceridemia (P= 0.006). Age
of the patient was significantly associated with hyperglycemia
(P=0.04), and hypercholesterolemia (P
= 0.003).

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Table 5 a. Associations between Risk factors and lipodystrophy in 356 HIV patients on HAART for one year
and above, at ART clinics of Tikur Anbessa Specialized Hospital, July 2007 to January 2008.
Risk factors Total Lipoatrophy
X 2 test
P-value
Lipohypertrophy
X 2 test
P-value
Sex Males 95 2.43 0.14 13.04 0.0001
Females
261
History of smoking: 24 6.06 0.01 4.7 0.03
Yes
No 330
Female
283 0.55 0.49 11.4 0.001
WC > 88 cms.
< 88 cms. 67
ART Regimen
Stavudine
209 4.9 0.03 0.06 0.83
based
Zidovudine
147
based
Duration of ART treatment
12-18 months 128 8.4 0.01 6.6 0.03
19-24 months
> 24 months
81
112
Table 5 b. Associations between Risk factors and metabolic abnormalities in 319 HIV on HAART for one year
and above, at ART clinics of Tikur Anbessa Specialized Hospital , July 2007 to January 2008.
Risk factors
Total
Fasting Plasma
glucose
X 2 test
p-value
Total Cholesterol
X 2 test
P-value
Age >50 years 28 5.04 0.04 9.7 0.003
88 cms. 255 4.9 0.03 6.3
< 88 cms. 59
Stage of HIV
Stage I&II 58 4.0 0.04 0.09 0.17
Stage III & IV 260
Sex Males 82 0.15 0.70 11.1 0.002
Females 237
Female
WC > 88 cms. 255 6.2 0.02 4.9 0.02
< 88 cms. 59
Duration of ART
treatment
12-18 months 114 10.2 0.006 0.9 0.6
19-24 months
> 24 months
74
97

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DISCUSSION
Barbaro and Lacobellis stated that about pathogenesis
of HAART associated metabolic syndrome and its
atherogenic profile is complex. It is stated, several
factors are involved including direct effects of
HAART on lipid metabolism, endothelial and adipocyte
cell function, activation of proinflammatory
cytokines and mitochondrial dysfunction (21). Mitochondrial
toxicity of NRTIs leads to metabolic abnormalities.
Stavudine- didanosine- zidovudine are
associated with greater toxicity than newer agents
like lamuvidine- abacavir- tenofivir (7).
In this study, among ART patients with metabolic
abnormalities the overall prevalence of lipodystrophy
was 68.3%, lipoatophy was 57.3%, and lipohypertrophy
was 46%. This was similar to a report in
a cohort of African HIV patients from Senegal; the
prevalence of mild to sever lipodystrophy affected
65% of patients on stavudine - zidovudine - protease
inhibitors for 4-9 yrs of ART (22). Study from
Rwanda showed that about 81% of patient on
HARRT were on stavudin- lamuvidine - nevirapine
regimen. Among these lipodystophy was observed in
69.6% in those receiving HARRT for more than 72
weeks (23).
Our study showed higher prevalence of lipodystrophy
compared to Rwandan study by Van Griensven
et al. Which showed the prevalence of lipodystrophy
in 34% and the prevalence of lipoatrophy was
three times higher when taking d4T compared with
AZT containing regimens (31.4% vs 10.3%) (24 ).
Others reported prevalence of lipodystrophy in 0-
38% patients treated with NRTI (25, 26). In the current
study, the prevalence of lipodystrophy is increasing
with increasing duration of HAART treatment
similar to that of report by Merceir S et al.
(22). Other report also showed that additional 6
months of treatment with HAART is associated with
a 45% increase risk of lipodystrophy (27).
Dyslipaedemia is common in persons with HIV infection.
The typical pattern is elevated total cholesterol
and low density lipoprotein (LDL), decreased
HDL cholesterol and elevated triglyceride (1,2,3).
In our study, the overall prevalence of Hyperlipademia
in 319 HIV patients on HAART was 56.9%.
Among these we found out high prevalence of hypercholesterolemia
(38.2%), low density lipoprotein
(54.2%) and low prevalence of triglyceride (15.2% ).
Gazzaruso et al showed a prevalence of hypertriglyceredimea
in 59.3% of 553 HIV patients on HAART
compared to our study which was only 15.2% (28).
A study from South African identified significantly
high level of cholesterol and triglyceride in HIV patients
on first line ART regimen containing Stavudine
(29).
Diabetes mellitus is found to be three times more
prevalent among patients receiving HAART (30).
Impaired glucose tolerance and diabetes in these patients
occurred due to primary mechanism of insulin
resistance and hyperinsulinemia (31). Previous reports
showed prevalence of hyperglycemia in 14 -24
% of patients in HAART (32, 33) compared to our
study (17.9%). In the current study prevalence of
Impaired Fasting Glucose (IFG) (10.9%) was low
compared to Study by Mutimura et al. from Rawanda
(18%) (23). Frank diabetes mellitus occured in 7% of
our patients compared to other reports (5-7% )(32-
34). History of smoking occurred in 6.8% of our
patients and it was significantly associated with lipoatrophy
and Lipohypertrophy, which is one of the
modifiable risk factor for lipodystrophy.
This is a cross sectional study of patients at a tertiary
medical center, which didn't include patients from
primary care settings. Only few patients were examined
by a physician, majority of patients were examined
by trained nurses from the ART clinic, this
might have some inter observer variations on physical
examination of the patients.
In conclusion: Lipohypertrophy and Lipoatrophy
occurred in most patients on HARRT treatment, hyperlipaedemia
and hyperglycaemia were seen in
Ethiopian HIV patients on HAART. We recommend:
Careful monitoring of metabolic abnormalities and
examination of the patient for early detection of the
side effect of highly active antiretroviral therapy.
Changing the regimen of HAART to less toxic drugs
and treating metabolic complications as early as possible.
ACKNOWLEDGEMENTS
We thank the Ethiopian Science and Technology
Commission and Research Publication Office of
Addis Ababa University for funding the research, Dr.
Wondwossen Amogne and Dr. Teshale Seboxa from
Infectious disease Division , Department of Internal
Medicine for management of the patients, Dr. Getu
Debela for patient management, organizing and assisting
in data collection Sr. Etenesh Kabtyemer, Sr.
Marta Hiba, Sr. Lemelem Alemayehu for data collection,
Ato Henoke Metaferia for data management.

229
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