Вы находитесь на странице: 1из 7

12

Rev Panam Infectol 2011;13(2):12-18. Rev Panam Infectol 2011;13(2):12-18.


ARTCULO ORIGINAL/ARTIGO ORIGINAL
Metabolic syndrome among HIV-infected
outpatients from a hospital in Quito, Ecuador:
a cross-sectional study
Sndrome metablico en pacientes ambulatorios VIH-positivos de un hospital
en Quito, Ecuador: un estudio transversal
Mauricio Fernando Villamar
1,2

Ana Cristina Albuja
2
Nelson Ignacio Cevallos Salas
2,3
1
Research Fellow. Laboratory of Neuromo-
dulation. Spaulding Rehabilitation Hospital.
Harvard Medical School, Boston, MA, U.S.A.
2
Facultad de Medicina. Ponticia Universi-
dad Catlica del Ecuador, Quito, Ecuador.
3
Mdico Tratante. Clnica de VIH/SIDA.
Servicio de Medicina Interna. Hospital Dr.
Enrique Garcs, Quito, Ecuador.
Rev Panam Infectol 2011;13(2):12-18.
Conicto de intereses: ninguno
Recibido en 29/10/2010.
Aceptado para publicacin en 23/5/2011.
Abstract
Objective: To determine metabolic syndrome (MS) prevalence among
patients from a HIV/AIDS clinic as dened by the National Cholesterol
Education Program Adult Treatment Panel III (ATP III) and Internatio-
nal Diabetes Federation (IDF) criteria, analyzing the association with
demographic, disease- and treatment-related variables. Methods: In
this cross-sectional study, 114 consecutive HIV-infected outpatients
were analyzed. Through a survey and review of medical records, data
were obtained regarding cardiovascular risk factors, disease staging and
scheme of highly active antiretroviral therapy (HAART) received. Pre-
sence of MS was then evaluated using the ATP III and IDF denitions.
Cohens kappa coefcient was calculated to determine concordance
between them. Variables showing a univariate relationship with the MS
were included in an unconditional logistic regression analysis model.
Results: MS prevalence was 35.1% when using ATP III criteria and
29.8% according to IDF. Kappa coefcient between denitions was
0.88. Prevalence was 26.9% among males and 46.8% among females
(ATP III) [OR 2.39 (1.09-5.26), p=0.009]. Individuals currently under
protease inhibitors for more than twelve months had signicantly higher
triglyceridemia as compared to nave patients or those receiving different
schemes (293199 vs. 194 98mg/dL,p=0.01). Only age older than
30 years [OR 3.16 (1.15-8.7), p=0.02] and body mass index (BMI)
> 25 kg/m
2
[OR 5.65 (2.17-14.73), p=0.0004] were signicant and
independently associated with MS on logistic regression analysis. Con-
clusions: Traditional risk factors seem to be more strongly linked to the
development of MS in HIV-positive Hispanics than those related to the
virus itself and HAART. Timely diagnosis and management of metabolic
disorders are key issues in this population.
Key words: Human immunodeciency virus (HIV), metabolic syn-
drome X (MS), highly active antiretroviral therapy (HAART), protease
inhibitors (PI).
Resumen
Objetivo: Determinar la prevalencia de sndrome metablico (SM) en
pacientes de una Clnica de VIH/SIDA segn las deniciones ATP III e
IDF, analizando su asociacin con variables demogrcas, de la enferme-
13
Villamar MF, Albuja AC Mctabolic syndromc among HIV-infcctcd out...
dad y su tratamiento. Mtodos: Este estudio transversal
incluy 114 pacientes ambulatorios consecutivos. Me-
diante una encuesta y revisin de historias clnicas se
obtuvo informacin sobre riesgo cardiovascular, estadio
de la enfermedad y esquema de terapia antirretroviral.
Posteriormente se evalu la presencia de SM segn
criterios IDF y ATP III; el ndice kappa de Cohen () se
calcul para determinar su concordancia. Las variables
que mostraron relacin univariada con el SM se incluye-
ron en la regresin logstica incondicional. Resultados:
La prevalencia de SM fue 35.1% segn los criterios ATP
III y 29.8% mediante IDF. El valor de fue 0.88. La
prevalencia fue 26.9% en varones y 46.8% en mujeres,
segn ATP III [OR 2.39 (1.09-5.26), p=0.009]. Los
pacientes actualmente bajo inhibidores de proteasa
(IP) por lapsos mayores a doce meses presentaron tri-
gliceridemia signicativamente mayor que aquellos sin
tratamiento o bajo otros esquemas (293 199 vs. 194
98mg/dL, p=0.01). Slo la edad mayor a 30 aos [OR
3.16 (1.15-8.7), p=0.02] y un ndice de masa corporal
(IMC) * 25 kg/m
2
[OR 5.65 (2.17-14.73), p=0.0004]
se asociaron signicativa e independientemente con el
desarrollo de SM en la regresin logstica incondicional.
Conclusiones: Factores de riesgo tradicionales estaran
ms fuertemente asociados con el desarrollo de SM
en pacientes hispanoamericanos VIH-positivos que
aquellos propios del virus y la terapia. El diagnstico y
manejo oportunos de los desrdenes metablicos son
fundamentales en esta poblacin.
Palabras clave: Virus de la inmunodeficiencia
humana (VIH), Sndrome X metablico, Terapia an-
tirretroviral altamente activa (TARAA), Inhibidores de
proteasa (IP).
Introduction
Highly active antiretroviral therapy (HAART) has
unquestionably transformed the natural history of hu-
man immunodeciency virus (HIV) infection, leading
to a signicant reduction in morbidity and mortality
associated with this agent.
(1)
However, long-term toxi-
city of HAART has been recognized and a new variety
of disorders has gained importance in patients treated
with this therapy.
Two decades ago it became evident that dys-
lipidemia and lipoatrophy were relatively frequent
anomalies found in patients with the Acquired Immu-
nodeciency Syndrome (AIDS).
(2)
A clear association
has been demonstrated between HAART, particularly
when containing protease inhibitors (PI), and fat re-
distribution, hypertension and insulin resistance. It is
also known that the HIV-1 can induce a similar spec-
trum of metabolic abnormalities.
(3-9)
These disorders
can occasionally be associated, and have a negative
impact on patients health status and their adherence
to treatment.
Resistance to the effects of insulin on peripheral
glucose uptake and fatty acid metabolism can be seen
in individuals with abdominal obesity, a component
of HIV-associated lipodistrophy, occasionally leading
to the development of type 2 diabetes mellitus (DM).
Insulin resistance, hyperinsulinemia, hyperglycemia
and adipokines might lead to vascular endothelial
dysfunction, lipid prole abnormalities, hypertension
and vascular inammation, promoting the formation of
atherosclerotic plaques and predisposing to cardiovas-
cular disease.
(10)
These abnormalities are components
of the metabolic syndrome (MS).
Prevalence of the MS in Ecuadorian general po-
pulation is unclear. The only PubMed-indexed study
analyzing this topic reported an occurrence of 7.5%
among men and 20.1% among women from the city
of Quito.
(11)
Given the fact that prevalence of the MS
has never been studied in HIV-infected individuals in
Ecuador and that little research of this class has been
done in Latin America, this project seeks to address
this important issue.
Materials and methods
In this cross-sectional study, 114 consecutive
HIV-infected outpatients managed at the HIV/AIDS
Clinic of Hospital Dr. Enrique Garcs, a secondary
hospital in Quito, Ecuador, were studied over a period
of three months in 2009. After giving their informed
consent, all participants were asked to complete a self-
administered questionnaire with information regarding
age, sex, tobacco use, time since the diagnosis of HIV
infection, scheme and duration of antiretroviral therapy
(ART) received. Patients younger than 18 years of age,
those with history of liver failure, currently pregnant,
showing clinical signs of active AIDS or hospitalized
for any cause in the past three months were excluded.
Height, weight and waist circumference (WC)
were then assessed using standard methods. Once
the patient had rested for 10 minutes or more in a
silent room, blood pressure (BP) was measured in the
left arm with the elbow exed at heart level using a
Riester Exacta

sphygmomanometer (Rudolf Riester


GmbH, Bruckstr. 31 D-72417, Jungingen, Germany).
All readings were performed by the same researcher.
The next step was a review of the participants
medical records to collect information regarding known
duration of HIV infection, current and nadir CD4
+
cell
count, current and highest viral load, HIV disease sta-
ging according to the 1993 Centers for Disease Control
and Prevention (CDC) classication,
(12,13)
scheme and
duration of HAART received, and the most recent de-
termination of fasting blood glucose and lipid prole.
14
Rev Panam Infectol 2011;13(2):12-18. Rev Panam Infectol 2011;13(2):12-18.
In all cases, CD4
+
lymphocyte cell count was deter-
mined in a BD FACSCount ow cytometer (BD Bios-
ciences, 2350 Qume Dr, San Jose, CA 95131, U.S.A.).
A COBAS TaqMan 48 analyzer (Roche Molecular
Systems Inc., 11 Franklin Ave, Belleville, NJ 07109,
U.S.A.) was used in order to assess HIV-1 RNA viral load.
Glucose was measured by the oxidase method. Tri-
glycerides were quantied using enzymatic methods in
a Gilford Stasar III semiautomatic spectrophotometer
(Gilford Instrument Laboratories Inc., 132 Artino St,
Oberlin, OH 44074, U.S.A.). HDL cholesterol (HDL-c)
was measured using separation by precipitation with
phosphotungstic acid and magnesium chloride.
Presence of the MS was then evaluated using the
2005 National Cholesterol Education Program Adult
Treatment Panel III (ATP III) and International Diabetes
Federation (IDF) denitions, with the cutoff points
recommended for Hispanic individuals. It should be
noted that the former are identical to the ones pu-
blished as a consensus in 2009,
(14)
when applied to
Ethnic Central and South Americans.
According to ATP III, patients with three or more of
the following parameters were classied as having MS:
fasting blood glucose > 100mg/dL or drug treatment
for elevated blood glucose; HDL-c < 40mg/dL in men
or < 50 mg/dL in women or pharmacologic treatment
with brates or niacin; triglycerides > 150mg/dL
or pharmacologic treatment with brates or niacin;
WC > 90cm in men or > 80cm in women; and BP
> 130/85mmHg or drug treatment for hypertension.
(15)
In contrast, IDF requires a WC > 90cm in men or
> 80cm in women and two or more of the follo-
wing parameters: fasting blood glucose > 100mg/
dL or diagnosed DM; HDL-c < 40 mg/dL in men or
< 50 mg/dL in women or pharmacologic treatment for
low HDL-c; triglycerides > 150 mg/dL or drug treatment
for elevated triglycerides; and BP > 130/85 mmHg or
drug treatment for hypertension.
(16)
Ethics
Every patient included in this study signed an
informed consent describing the purposes of the inves-
tigation in detail, and the privacy of their information
remained protected at all times. The protocol of the
study was approved by the local Ethics Committee. This
research complies with the ethical principles stated
in the Declaration of Helsinki of the World Medical
Association, as revised in 2008.
(17)
Statistics
Students t test was carried out in order to assess
differences between two means. The Mann-Whitney U
test was used when data were not normally distribu-
ted. To assess the degree of association of categorical
variables, either
2
test or Fishers exact test were
performed. The 95% condence intervals for propor-
tions were calculated using the efcient score method,
corrected for continuity. In all cases, a two-tailed p-
value < 0.05 was considered statistically signicant.
Analyzed variables included age, sex, body mass in-
dex (BMI), HIV clinical stage (according to the CDC clas-
sication), current and nadir CD4
+
cell count, plasma
HIV RNA categorized as detectable (* 400 copies/ml)
or undetectable, duration of and type of ART received.
Variables showing a univariate relationship with
the MS were included in the unconditional logistic re-
gression analysis model. Those incorporated were sex,
age (dichotomized as younger or older than 30 years),
BMI (lower or greater than 25 kg/m
2
), ART exposure,
HIV clinical stage, and CD4
+
nadir cell count (lower or
greater than 200/L). Goodness of t was veried using
the likelihood ratio test and the score test. Cohens
kappa coefcient was calculated in order to determine
concordance between ATP III and IDF criteria.
All statistical analyses of database results were
Table 1. Demographic, anthropometric and HIV-related
characteristics of the sample
Parameters Values
Age (years) 36.76 11.51
Men/Women 67/47
Weight (kg) 62.05 10.2
Men 65.21 9.79
Women 57.54 9.08
Height (cm) 161.41 9.00
Men 167.04 5.68
Women 153.38 6.38
BMI (Kg/m
2
) 24.21 6.07
Men 24.06 7.34
Women 24.42 3.64
Waist circumference (cm) 85.62 8.22
Men 85.68 8.77
Women 85.53 7.44
Current smokers (%) 13 (11.4)
Known duration of HIV infection [months (IQR)] 27 (12-50)
CD4
+
nadir cell count [x 10
6
cells/l (IQR)] 169 (88-263)
Current CD4
+
cell count [x 10
6
cells/l (IQR)] 284 (176-435)
Viral load <400 copies/ml (%) 83 (73.5)
HIV disease staging (%)
a

A 29 (25.44)
B 47 (41.22)
C 38 (33.33)
Median HAART duration [months (IQR)] 19 (8-39)
HAART exposure (%)
Nave 13 (11.4)
Never PI exposure 62 (54.4)
Never D4T exposure 87 (76.3)
Past PI 9 (7.9)
Current PI 30 (26.3)
Past D4T 13 (11.4)
Current D4T 1 (0.9)
Data are means standard deviation and n (%), unless otherwise indicated.
a
A: asymptomatic, acute HIV, or persistent generalized lymphadenopathy; B: symp-
tomatic, not A or C categories; C: AIDS indicator conditions.
BMI, body mass index; HIV, human immunodeciency virus; IQR, interquartile range;
HAART, highly active antiretroviral therapy; PI, protease inhibitors; D4T, stavudine.
15
Villamar MF, Albuja AC Mctabolic syndromc among HIV-infcctcd out...
Table 2. Prevalence of metabolic anomalies among
patients
Variables n (%)
Waist circumference
> 90cm in men 21 (31.3)
> 80cm in women 31 (66.0)
Blood pressure > 135/85mmHg 16 (14.0)
Triglycerides > 150mg/Dl 72 (63.2)
HDL-c
< 40mg/dL in men 33 (49.3)
< 50mg/dL in women 32 (68.1)
Glucose > 100mg/dL 37 (32.5)
HDL-c: high-density lipoprotein cholesterol
Table 3. Demographic, anthropometric and HIV-related characteristics among patients with and without the MS,
according to the ATP III and IDF denitions
ATP III IDF
MS present MS absent p MS present MS absent p
n (%) 40 (35.1) 74 (64.9) 34 (29.8) 80 (70.2)
Age (years) 40.55 11.20 34.72 11.21 0.0092 39.18 11.27 35.74 11.52 NS
Sex (%) 0.0157 0.0022
Men 18 (26.9) 49 (73.1)
OR 2.39 (1.09-5.26)
13 (19,4) 54 (80.6)
OR 3.35 (1.45-7.73)
Women 22 (46.8) 25 (53.2) 21 (44.7) 26 (55.3)
Current smokers (%) 3 (23.1) 10 (76.9) NS 3 (8.8) 10 (12.5) NS
BMI (Kg/m
2
) 25.64 3.56 23.44 6.97 NS 26.19 3.43 23.36 6.74 0.0000
Known duration of HIV infection [months (IQR)] 28 (16-55) 25 (10-50) NS 27.5 (17-50) 26.5 (10.5-50.5) NS
CD4
+
nadir cell count [x 10
6
cells/l (IQR)] 206 (130-260) 152 (77-295) NS 216 (159-258) 151 (80-289) NS
Current CD4
+
cell count [x 10
6
cells/l (IQR)] 311 (244-428) 272 (149-438) NS 311 (244-427) 272 (149-448) NS
Current viral load (%) 0.0058 0.0091
Undetectable (< 400 copies/L) 35 (42.2) 48 (57.8)
OR 0.27 (0.09-0.79)
30 (36.1) 53 (63.9)
OR 0.27 (0.09-0.85)
Detectable (> 400 copies/L) 5 (16.7) 25 (83.3) 4 (13.3) 26 (86.7)
HIV disease staging (%)
a
A 10 (25.0) 19 (25.67) NS 10 (29.41) 19 (23.75) NS
B + C 30 (75.0) 55 (74.33) 24 (70.59) 61 (76.25)
Median HAART duration [months (IQR)] 24 (11-44) 16 (7-33) NS 22 (9-42) 17 (8-36) NS
HAART exposure (%)
Nave 3 (7.5) 10 (13.5) NA 3 (8.8) 10 (12.5) NA
Never PI 23 (57.5) 39 (52.7) NA 18 (52.9) 44 (55.0) NA
Never D4T 29 (72.5) 58 (78.4) NA 24 (70.6) 63 (78.8) NA
Past PI 3 (7.5) 6 (8.1) NA 3 (8.8) 6 (7.5) NA
Current PI 11 (27.5) 19 (25.7) NA 10 (29.4) 20 (25.0) NA
Past D4T 7 (17.5) 6 (8.1) NA 6 (17.6) 7 (8.8) NA
Current D4T 1 (2.5) 0 (0.0) NA 1 (2.9) 0 (0.0) NA
Data are means standard deviation and n (%), unless otherwise indicated;
a
A: asymptomatic, acute HIV, or persistent generalized lymphadenopathy; B: symptomatic, not
A or C categories; C: AIDS indicator conditions; MS, metabolic syndrome; NS, not signicant; BMI, body mass index; BP, blood pressure; HDL-c: high-density lipoprotein
cholesterol; HIV, human immunodeciency virus; IQR, interquartile range; HAART, highly active antiretroviral therapy; PI, protease inhibitors; D4T, stavudine; NA, not applicable.
performed with EpiInfo

version 3.5.1,
(18)
except for
Cohens kappa index, determined through an online
calculator.
(19)
Results
One hundred and fourteen outpatients from Hospi-
tal Dr. Enrique Garcs HIV/AIDS Clinic were included in
this research. Characteristics of the sample are shown
in table 1. Thirteen patients (11.4%) were nave, and
101 (88.6%) were HAART-experienced. Of those in-
dividuals currently under PI at the time of the study,
63.3% (n=19) had been taking such drugs for longer
than twelve months.
One or more features of the MS were seen in
103 (90.25%) patients. The most common triad was
hypertriglyceridemia, abdominal obesity and low HDL-c
(n=25). Frequency of metabolic abnormalities associa-
ted with the MS is represented in table 2.
Prevalence of the MS in the sample was 35.1%
(n=40) when using ATP III criteria and 29.8% (n=34)
according to IDF. Prevalence in men was 26.9% (n=18)
and 19.4% (n=13), respectively. In women, it was
46.8% (n=22) and 44.7% (n=21). Concordance betwe-
en these two denitions, calculated with Cohens kappa
coefcient () was 0.88, with a standard error of 0.09.
Table 3 shows demographic, anthropometric and HIV-
related variables in patients with and without the MS.
MS prevalence showed a direct relationship with
age, increasing from 18.4% in the 18-to-30-years
age group to 57.1% in individuals 51 years of age
and older. Mean age was higher in patients diagno-
sed with MS according to ATP III and IDF criteria as
compared to those who did not have it. Nevertheless,
the results were statistically signicant only for the
former (p=0.0092).
Among patients on HAART, 36.6% were diagnosed
with MS using ATP III criteria and 30.7% according to
IDF. When comparing HAART-experienced with nave
individuals, we found that the former were signi-
cantly older (37.8 11.68 vs. 28.69 5.41 years,
p=0.0029) and their triglyceride levels higher (220.00
128.39 vs. 133.53 63.15 mg/dL, p=0.0068).
Mean glycemia was found to be more elevated in
16
Rev Panam Infectol 2011;13(2):12-18. Rev Panam Infectol 2011;13(2):12-18.
patients on HAART (94.80 17.77 vs. 85.62
10.58 mg/dL, p=0.06) and, as opposed to what was ex-
pected, HDL-c readings were signicantly higher in ma-
les who receive such drugs (42.22 15.3 vs. 31.12
9.09 mg/dL, p=0.05).
The only statistically signicant difference found
when comparing patients currently receiving PI for
more than twelve months with nave individuals or tho-
se taking them for shorter periods was triglyceridemia,
markedly higher in the former (293.21 199.25 vs.
193.53 98.42 mg/dL, p=0.0120).
An unconditional logistic regression analysis model
was performed in order to assess the effect of indepen-
dent variables on MS diagnosis. The only ones found to
be signicant and independently associated with the
MS were age older than 30 years [OR 3.16 (1.15-8.7),
p=0.02] and overweight, dened as a BMI > 25Kg/m
2

[OR 5.65 (2.17-14.73), p=0.0004].
Discussion
Prevalence of the MS in our sample was found to be
higher than that reported by other studies, which varies
between 14 and 26% according to ATP III criteria.
(20-27)
It should be noted that the 2005 ATP III criteria
employed in our research
(15)
agree with the 2009
consensus recommendation
(14)
of using the same WC
cutoff points suggested for Southeast Asians in Ethnic
Central and South Americans (> 80 cm in women and
> 90 cm in men) until more data are available.
MS occurrence among males from our sample did
not differ much from that reported in international
studies with HIV-positive populations;
(20,24)
however it
was markedly higher in women. Such ndings could be
explained by the higher frequency of MS in Hispanic
women as compared to other ethnic groups found in
general population studies. Ford et al.
(28)
reported a
MS prevalence of 20.5% in Mexican-American males
and 35.5% in females. Prevalence among males was
similar to that among Caucasians; however, it was sig-
nicantly higher in Mexican-American women than in
any other ethnic group. Similar ndings were published
by Park et al.
(29)
The higher predisposition to developing MS seen
in women could be due to biologic, psychological and
environmental factors. The higher percentage of body
fat in females determines lower energy expenditure per
kilogram. Some studies have also found an association
between the number of pregnancies and obesity
(30)
.
Moreover, menopause has an adverse effect on body
composition and metabolic parameters, leading to an
increased likelihood of developing obesity.
(31)
Psycho-
logical factors can be either a cause or a consequence
of obesity, and females are known to have a higher
frequency of eating disorders.
(32)
Finally, environmental
factors could also play a role in women, because the
portions they eat are often larger than their needs, since
their energy requirements are lower than mens due to
their phenotype and level of activity.
(30)
CARMELA,
(11)

the only PubMed-indexed research to analyze the pre-
valence of MS in an Ecuadorian general population,
found MS to be present in 7.5% of males and 20.1%
of females, which corroborates womens tendency to
develop such anomalies. However, CARMELA employed
WC cutoff points suggested for Caucasians and glyce-
mia higher than 110mg/dL as criteria for dening MS,
which could lead to underdiagnosis. Anyway, given
the evidence of an increased likelihood of developing
metabolic anomalies, Hispanic women should be
particularly targeted for their early identication and
management.
It seems to be that prevalence of the MS is higher
among HIV-infected individuals as compared to the
general population in Ecuador. However, more studies
with standardized denitions are needed in order to
verify this assertion.
Tobacco use did not show an association with
the development of MS in our sample, nor in other
studies.
(20,21,24)
After unconditional logistic regression analysis was
carried out, only age older than 30 years and overweight
(BMI > 25 Kg/m
2
) were signicant and independently
associated with the development of MS. These results
are similar to those reported by Jeric et al. in a study
with 710 HIV-positive Spanish patients.
(20)
Even though
the relationship between overweight and MS would
seem quite obvious, age is not always taken into ac-
count as a risk factor. Therefore, both identication and
control of metabolic anomalies become fundamental
as patients grow older.
Concordance between ATP III and IDF criteria
was almost perfect,
(33)
with =0.88. This value is
comparable to that reported by Guerrero-Romero
(34)
in
a Mexican general population study (=0.873), but
differs from the moderate concordance found by Sa-
maras et al.
(24)
in HIV-infected individuals (=0.46). It
should be noted that we employed the same WC cutoff
points as Guerrero-Romero, while Samaras used those
recommended for Caucasians. Since this parameter is
mandatory in the IDF denition for the MS, the lower
the WC required the higher the concordance will be.
Our ndings suggest that ATP III and IDF criteria are
equally valid for the diagnosis of MS in Hispanics.
Variables such as current CD4
+
cell count and time
since the diagnosis of HIV infection was made were
not signicantly associated with the presence of MS
in our research or in Jerics.
(20)
Samaras
(24)
did nd a
statistically signicant relation between the duration of
HIV infection and the development of metabolic ano-
17
Villamar MF, Albuja AC Mctabolic syndromc among HIV-infcctcd out...
malies, probably due to the more prolonged use of ART.
Among patients from Hospital Dr. Enrique Garcs
HIV/AIDS Clinic, detectable viral load values were
inversely related to the presence of MS [OR 0.27
(CI 95% 0.09-0.79), p=0.0058]. Similar ndings
were reported by Estrada et al.,
(35)
while three other
studies
(21,36,37)
found no signicant association between
both variables. This can be explained by the use of
HAART, which increases the risk of presenting meta-
bolic anomalies while decreasing viral replication rate.
Since HAART, especially when containing PI, is a
known predisposing factor to developing MS, it is likely
that a statistically signicant association between these
two variables could have been found if the sample size
were larger. Given the high prevalence of MS among
Hispanics, it is also possible that it was present in some
patients prior to the initiation of HAART.
Many of the metabolic anomalies seen in HIV-
infected individuals are often attributed to HAART.
Cohort studies have demonstrated that PI use is
associated with the development of dyslipidemia and
other metabolic disorders,
(38)
particularly signicant
elevations in serum cholesterol and triglycerides.
(39-41)

In our study, individuals currently under PI for twel-
ve months or more were found to have signicantly
higher triglyceridemia as compared to nave patients
or those who received PI for shorter periods (293
199 vs. 194 98mg/dL, p=0.0120).
When HDL-c levels were analyzed, signicantly
higher values were found in male individuals on HAART
versus naves. Such ndings could seem paradoxical,
because PI-based schemes tend to reduce HDL-c
levels.
(39-41)
However, use of non-nucleoside reverse
transcriptase inhibitors (NNRTI) has been reported to
decrease the risk of having low HDL-c
(8,41,42)
and since
78.2% (n=79) of patients on HAART at Hospital Dr.
Enrique Garcs are under efavirenz-containing sche-
mes, these results can be justied.
Even though the difference between serum glucose
means in HAART-experienced and nave individuals was
not statistically signicant (p=0.06), it does correlate
with ndings reported in other studies which show a
predisposition to higher glucose levels in the latter.
(43,44)
The results of our research suggest that tradi-
tional risk factors are more strongly associated with
the development of the MS in HIV-positive Hispanic
individuals than those related to the virus itself and
HAART. Therefore, timely diagnosis and management
of metabolic disorders, emphasizing the importance
of healthy lifestyles, are key issues in this population.
Acknowledgements
The authors would like to thank Dr. Rosa Polo,
M.D., PhD (Plan Nacional Sobre el SIDA, Madrid,
Spain) and LCDR Matthew T. Brigger, M.D., M.P.H.
(Naval Medical Center San Diego Department Of Oto-
laryngology Head and Neck Surgery, San Diego, CA,
U.S.A.), for reviewing the Spanish and English versions
of this manuscript, respectively.
References
1. May MT, Sterne JA, Costagliola D, Sabin CA, Phillips AN, Justice
AC, et al. HIV treatment response and prognosis in Europe and
North America in the rst decade of highly active antiretroviral
therapy: a collaborative analysis. Lancet. 2006;368:451-8.
2. Grunfeld C, Kotler DP, Hamadeh R, Tierney A, Wang J, Pierson
RN. Hypertrygliceridemia in the acquired immunodeciency
syndrome. Am J Med. 1989;86:27-31.
3. Leow MKS, Addy CL, Mantzoros CS. Human Immunodeciency
Virus/Highly Active Antiretroviral Therapy-Associated Metabolic
Syndrome: Clinical Presentation, Pathophysiology, and Therapeu-
tic Strategies. J Clin Endocrinol Metab. 2003;88(5):1961-76.
4. Kino T, Gragerov A, Slobodskaya O, Tsopanomichalou M, Chrou-
sos GP, Pavlakis GN. Human immunodeciency virus type 1
(HIV-1) accessory protein Vpr induces transcription of the HIV-1
and glucocorticoid-responsive promoters by binding directly to
p300/CBP coactivators. J Virol. 2002;76(19):9724-34.
5. Imami N, Antonopoulos C, Hardy G, Gazzard B, Gotch FM. As-
sessment of type 1 and type 2 cytokines in HIV type 1-infected
individuals: impact of highly active antiretroviral therapy. AIDS
Res Hum Retroviruses. 1999;15(17):1499-1508.
6. Ledru E, Christeff N, Patey O, de Truchis P, Melchior JC,
Gougeon ML. Alteration of tumor necrosis factor- T-cell home-
ostasis following potent antiretroviral therapy: contribution to
the development of human immunodeciency virus-associated
lipodystrophy syndrome. Blood. 2000;95(10):3191-8.
7. Shrivastav S, Kino T, Cunningham T, Ichijo T, Schubert U,
Heinklein P, et al. Human Immunodeciency Virus (HIV)-1
Viral Protein R Suppresses Transcriptional Activity of Peroxi-
some Proliferator-Activated Receptor and Inhibits Adipocyte
Differentiation: Implications for HIV-Associated Lipodystrophy.
Mol Endocrinol. 2008;22:234-47.
8. Wadhwa S, Mukherjee S. Epidemiology and pathogenesis
of dyslipidemia and cardiovascular disease in HIV-infected
patients. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham,
MA, 2009.
9. Mujawar Z, Rose H, Morrow M, Pushkarsky T, Dubrovsky L,
Mukhamedova N, et al. Human immunodeciency virus impairs
reverse cholesterol transport from macrophages. PLoS Biol.
2006;4(11):e365, 1970-83.
10. Meigs J. The metabolic syndrome (insulin resistance syndrome
or syndrome X). In: UpToDate, Basow, DS (Ed), UpToDate,
Waltham, MA, 2009.
11. Schargrodsky H, Hernndez-Hernndez R, Champagne BM,
Silva H, Vinueza R, Silva Ayaguer LC, et al. CARMELA: Asses-
sment of Cardiovascular Risk in Seven Latin American Cities.
Am J Med. 2008;121(1):58-65.
12. Centers for Disease Control and Prevention: 1993 Revised clas-
sication system for HIV infection and expanded surveillance
case denition for AIDS among adolescents and adults. MMWR
Recomm Rep. 1992;41:119.
13. Bartlett J. The stages and natural history of HIV infection. In:
UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2009.
14. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI,
Donato KA, et al. Harmonizing the Metabolic Syndrome: A Joint
Interim Statement of the International Diabetes Federation
Task Force on Epidemiology and Prevention; National Heart,
18
Lung, and Blood Institute; American Heart Association; World
Heart Federation; International Atherosclerosis Society; and
International Association for the Study of Obesity. Circulation.
2009;120:1640-5.
15. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH,
Franklin BA, et al. Diagnosis and Management of the Metabolic
Syndrome: An American Heart Association/National Heart,
Lung, and Blood Institute Scientic Statement: Executive
Summary. Circulation. 2005;112:e285-90.
16. Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome
a new world-wide definition. A Consensus Statement
from the International Diabetes Federation. Diabet Med.
2005;23:46980.
17. WMA Declaration of Helsinki - Ethical Principles for Medical
Research Involving Human Subjects. Seoul, Korea: World Me-
dical Association; October 2008. Available from: http://www.
wma.net/en/30publications/10policies/b3/index.html
18. Epi Info [computer program]. Version 3.5.1. Atlanta, GA:
Centers for Disease Control and Prevention, 2008.
19. Olmos A. Online Cohens Kappa Calculator, 2007. Available
from: http://olmosantonio.com/kappa-calculator/online.html.
Accessed 30 March 2010.
20. Jeric C, Knobel H, Montero M, Ordez-Llanos J, Guelar A,
Gimeno JL, et al. Metabolic Syndrome Among HIV-Infected
Patients: Prevalence, characteristics, and related factors.
Diabetes Care. 2005;28:132-7.
21. Mondy K, Overton ET, Grubb J, Tong S, Seyfried W, Powderly
W, et al. Metabolic syndrome in HIV-infected patients from an
urban, midwestern US outpatient population. Clin Infect Dis.
2007;44:726-34.
22. Botero-Echeverry J, Hincapi-Acua M, Maya-Gallego C. Pre-
valencia de sndrome metablico en pacientes con infeccin
por VIH de Susalud EPS [abstract]. Available from: http://www.
susalud.com/memorias_prestadores/prevalencia_sindrome_me-
tab_vih.pdf. Accessed 5 April 2010.
23. Guevara FO, Can B, Livano MC, Lombo B, Rendn I, Blanco
F. Prevalencia de sndrome metablico en pacientes infectados
con VIH utilizando los criterios del ATP III y de la IDF. Acta
Med Colombiana. 2008;33(4):282-8.
24. Samaras K, Wand H, Law M, Emery S, Cooper D, Carr A. Preva-
lence of metabolic syndrome in HIV-infected patients receiving
highly active antiretroviral therapy using International Diabetes
Foundation and Adult Treatment Panel III criteria: Associations
with insulin resistance, disturbed body fat compartmentaliza-
tion, elevated C-reactive protein, and hypoadiponectinemia.
Diabetes Care. 2007;30(1):113-9.
25. Jacobson DL, Tang AM, Spiegelman D, Thomas AM,
Skinner S, Gorbach SL, et al. Incidence of Metabolic
Syndrome in a Cohort of HIV-Infected Adults and Preva-
lence Relative to the US Population (National Health and
Nutrition Examination Survey). J Acquir Immune Defic
Syndr. 2006;43(4):458-66.
26. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormali-
ties in HIV-infected adults. N Engl J Med. 2005;352(1):48-62.
27. Mangili A, Jacobson DL, Gerrior J, Polak JF, Gorbach SL, Wanke
CA. Metabolic syndrome and subclinical atherosclerosis in
patients infected with HIV. Clin Infect Dis. 2007;44:136874.
28. Ford ES, Giles WH, Dietz WH. Prevalence of the metabo-
lic syndrome among US adults: ndings from the Third
National Health and Nutrition Examination Survey. JAMA.
2002;287(3):356-9.
29. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR,
Heymseld SB. The metabolic syndrome: prevalence and asso-
ciated risk factor ndings in the US population from the Third
National Health and Nutrition Examination Survey, 1988-1994.
Arch Intern Med. 2003;163:427-36.
30. Garca-Garca E, De la Llata-Romero M, Kaufer-Horwitz
M, Tusi-Luna MT, Calzada-Len R, Vzquez-Velzquez V,
et al. La obesidad y el sndrome metablico como proble-
ma de salud pblica. Una reexin. Salud Pblica Mx.
2008;50(6):530-47.
31. Carr M. The Emergence of the Metabolic Syndrome with Me-
nopause. J Clin Endocrinol Metab. 2003;88(6):2404-11.
32. Faith MS, Matz PE, Jorge MA. Obesity-depression associations
in the population. J Psychosom Res. 2002;53(4):935-42.
33. Landis JR, Koch GG. The measurement of observer agreement
for categorical data. Biometrics. 1977;33:159-74.
34. Guerrero-Romero F, Rodrguez-Morn M. Concordance Be-
tween the 2005 International Diabetes Federation Denition
for Diagnosing Metabolic Syndrome With the National Cho-
lesterol Education Program Adult Treatment Panel III and
the World Health Organization Denitions. Diabetes Care.
2005;28(10):2588-9.
35. Estrada V, Martnez-Larrad MT, Gonzlez-Snchez JL, de Villar
NGP, Zabena C, Fernndez C, et al. Lipodystrophy and metabo-
lic syndrome in HIV-infected patients treated with antiretroviral
therapy. Metabolism. 2006;55:940-5.
36. Wand H, Calmy A, Carey DL, Samaras K, Carr A, Law MG, et
al. Metabolic syndrome, cardiovascular disease and type 2
diabetes mellitus after initiation of antiretroviral therapy in HIV
infection. AIDS. 2007;21:244553.
37. Bergersen BM, Schumacher A, Sandvik L, Bruun JN, Birke-
land K. Important differences in components of the metabolic
syndrome between HIV-patients with and without highly active
antiretroviral therapy and healthy controls. Scand J Infect Dis.
2006;38:6829.
38. Vigouroux C, Gharakhanian S, Salhi Y, Nguyen TH, Adda N,
Rozenbaum W, et al. Adverse metabolic disorders during highly
active antiretroviral therapy (HAART) of HIV disease. Diabetes
Metab. 1999;25:383-92.
39. Pujari S, Dravid A, Naik E, Bhagat S, Tash K, Nadler JP, et
al. Lipodystrophy and Dyslipidemia Among Patients Taking
First-Line, World Health OrganizationRecommended Highly
Active Antiretroviral Therapy Regimens in Western India. J
Acquir Immune Dec Syndr. 2005;39(2):199-202.
40. Dube M, Fenton M. Lipid Abnormalities. Clin Infect Dis.
2003;36(Suppl 2):S79-S83.
41. Fontas E, van Leth F, Sabin CA, Friis-Mller N, Ricken-
bach M, dArminio Monforte A, et al. Lipid Profiles in
HIV-Infected Patients Receiving Combination Antiretroviral
Therapy: Are Different Antiretroviral Drugs Associated with
Different Lipid Profiles? J Acquir Immune Defic Syndr.
2004;189:1056-74.
42. Barbaro G, Klatt EC. HIV Infection and the Cardiovascular
System. AIDS Rev. 2002;4:93-103.
43. Bonfanti P, Giannattasio C, Ricci E, Facchetti R, Rosella E,
Franzetti M, et al. HIV and Metabolic Syndrome: A Comparison
With the General Population. J Acquir Immune Dec Syndr.
2007;45:426-31.
44. Brown TT, Li X, Cole SR, Kingsley LA, Palella FJ, Riddler SA,
et al. Cumulative exposure to nucleoside analogue reverse
transcriptase inhibitors is associated with insulin resistan-
ce markers in the Multicenter AIDS Cohort Study. AIDS.
2005;19(13):1375-83.
Correspondence:
Dr. Mauricio Fernando Villamar
125 Nashua St. 7
th
Floor, Room 726.
Boston, MA, U.S.A.
e-mail: mvillamar@neuromodulationlab.org
Rev Panam Infectol 2011;13(2):12-18.

Вам также может понравиться