SUPPLEMENT ARTICLE
Insulin Resistance and Diabetes Mellitus Associated With
Antiretroviral Use in HIV-Infected Patients:
Pathogenesis, Prevention, and Treatment Options
Pablo Tebas, MD
Abstract: The contribution of current antiretroviral treatment
regimens to the long-term survival of HIV-infected individuals is
accompanied by increased risk of glucose metabolism abnormalities
in this patient population. The risk of insulin resistance and diabetes
in HIV-infected patients receiving antiretroviral treatment stems from
2 sources: exposure to the same environmental factors that have led
to an increased incidence of these conditions in the general popu-
lation and the negative effects on glucose metabolism inherent to
components of antiretroviral treatment regimens. This article reviews
the pathogenesis and diagnosis of insulin resistance and diabetes and
the contribution of components of antiretroviral therapy regimens to
increased risk for these conditions. Optimization of antiretroviral
treatment regimens for HIV-infected patients with or at increased risk
for development of abnormalities in glucose metabolism is discussed.
Key Words: antiretrovirals, diabetes mellitus, metabolic effects,
metabolic syndrome, insulin resistance, cardiovascular disease
(J Acquir Immune Defic Syndr 2008;49:S86S92)
INTRODUCTION
The metabolic syndrome is a constellation of findings
that encompasses defects in glucose metabolism, lipid meta-
bolism, and hypertension, with abdominal obesity and insulin
resistance playing a central role in its pathogenesis. Depending
on the definition used, it is estimated that 25%40% of
American adults have the metabolic syndrome,1,2 a diagnosis
of which requires the presence of at least 3 of the following
components: impaired glucose tolerance, hypertension, ele-
vated waist circumference or waist-hip ratio, and high trigly-
ceride and/or low high-density lipoprotein cholesterol (HDL-C)
levels.3 The presence of the metabolic syndrome increases the
risk of cardiovascular disease 3-fold4 and the development of
From the AIDS Clinical Trials Unit, University of Pennsylvania, Philadelphia, PA.
Disclosure: Dr. Tebas has received grant/research support from Boehringer
Ingelheim, Bristol-Myers Squibb Company, GlaxoSmithKline, Merck &
Co., Inc., Pfizer Inc, Roche Pharmaceuticals, Schering-Plough, Tibotec
Pharmaceuticals Limited, VGX Pharmaceuticals Inc., and VIRxSYS.
He is a consultant for Boehringer Ingelheim, Bristol-Myers Squibb
Company, Merck & Co., Inc., Tibotec Pharmaceuticals Limited, and VGX
Pharmaceuticals Inc.
Correspondence to: Pablo Tebas, MD, Associate Professor of Medicine,
University of Pennsylvania, Principal Investigator, AIDS Clinical Trials
Unit, 8 Penn Tower, 34th and Civic Center Boulevard, Philadelphia, PA
19104-4283 (e-mail: pablo.tebas@uphs.upenn.edu).
Copyright 2008 by Lippincott Williams & Wilkins
S86 J Acquir Immune Defic Syndr  Volume 49, Supplement 2, September 1, 2008
Copyright 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
frank diabetes.5,6 According to the American Diabetes Asso-
ciation (ADA) classification criteria, type 2 diabetes results
from a progressive defect in insulin secretion on a background
of insulin resistance.7 The risk of type 2 diabetes increases
with age, obesity, and lack of physical activityrisk factors
that can also affect HIV-positive individuals. Other risk factors
for developing type 2 diabetes include having a first-degree
relative with diabetes; being a member of a high-risk ethnic
population (eg, African American, Latino, Native American,
Asian American, and Pacific Islander); hypertension (blood
pressure $140/90 mm Hg); HDL-C ,35 mg/dL and/or
a triglyceride level .250 mg/dL; impaired glucose tolerance
or fasting glucose on previous tests; a history of cardiovascular
disease and/or other conditions associated with insulin resis-
tance; and, for women, a past diagnosis of gestational diabetes,
delivery of a baby weighing more than 9 lb, or presence of
polycystic ovarian syndrome.7 The pathology associated with
diabetes results primarily from a loss of glycemic control,
leading to abnormally increased levels of blood glucose.8 As is
also true for the general population, the high insulin levels and
insulin resistance frequently seen in HIV-positive individuals
are also associated with an increased risk of cardiovascular
events that are independent of lipoprotein levels; for every
standard deviation increase in insulin levels, the risk for
cardiovascular events increases by a factor of 1.6 (1.12.3).9
THE METABOLIC SYNDROME AND DIABETES
IN HIV-INFECTED PATIENTS
The success of highly active antiretroviral therapy
(HAART) has resulted in the prolongation of life for HIV-
positive individuals. This, in turn, has exposed this population
to the same environmental factors that have led to an epidemic
of obesity and diabetes in the general population of developed
societies.1,10 In addition, the side effects inherent to many
antiretroviral treatments can also significantly contribute to the
development of metabolic syndrome and diabetes. A recent
study evaluated the risk of developing metabolic syndrome for
up to 3 years postinitiation of antiretroviral therapy (ART).
Before ART, 8.5% of patients were diagnosed with metabolic
syndrome as per the criteria of the National Cholesterol
Education Program Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults, Third
Report (NCEP). During follow-up, 234 patients progressed to
metabolic syndrome that was significantly associated with
increased risk of both cardiovascular disease and type 2
diabetes.2 Several other studies have demonstrated that patients
J Acquir Immune Defic Syndr  Volume 49, Supplement 2, September 1, 2008
with HIV infection are also at increased risk of developing
diabetes compared with the general population.11,12
An assumption has been made that persons with
the metabolic syndrome receiving HAART are at similar
cardiovascular risk compared with HIV-seronegative individ-
uals with metabolic syndrome, but the phenotype often differs
between these 2 populations. In particular, HIV-infected
individuals tend to have significant peripheral lipoatrophy that
contributes to insulin resistance and elevated waist-hip ratio.
The frequency of this syndrome among HIV-positive
individuals varies according to the definition used in indi-
vidual studies and the patients ethnic background, consistent
with findings in the general population. The prevalence of
metabolic syndrome in HIV-infected individuals has been
reported as 18% in Spain,13 14%18% in a multinational
study,14 and 26% in a North American study.15 In general, the
prevalence among HIV-positive patients has not been reported
as higher than that among HIV-uninfected persons living in the
same community.
Recent studies also suggest that HIV-infected individ-
uals on HAART are developing diabetes at increasing rates12,16
and are likely to have a higher risk of cardiovascular disease.17
Thus, these observations lend support to the notion that
the metabolic syndrome is likely to predict a higher risk of
diabetes and cardiovascular disease in patients on HAART.2
As is true for the general population, by far the most frequent
diabetic phenotype associated with HIV infection is type 2
diabetes.18
EFFECTS OF ANTIRETROVIRAL DRUGS ON
INSULIN RESISTANCE
Studies evaluating the metabolic effects of antiretro-
viral drugs are conducted initially in in vitro systems and
animal models. These studies do not always extrapolate well to
humans and have a somewhat limited value in clinical practice;
however, they are critical for elucidation of the molecular
mechanism(s) of the side effects of these medications. Among
antiretrovirals, the only class that has been associated with
direct effects on glucose metabolism is the protease inhibitors.
The other classes of antiretroviral drugs exert their effects on
glucose metabolism indirectly by affecting changes to body
composition. The effects of nucleoside reverse transcriptase
inhibitors (NRTIs), particularly stavudine, on glucose metab-
olism are more indirect and related to lipoatrophy as a con-
sequence of long-term use.19 However, results of a recent study
of NRTI therapy with zidovudine or stavudine in 20 HIV-
negative individuals indicated a significant dysregulation in
expression of lipid and mitochondrial genes after only 6 weeks
of therapy, without accompanying changes in body composition.20
Protease Inhibitors
The frequent reports of diabetes and insulin resistance
during the initial years of availability of potent ART led the US
Food and Drug Administration in 1997 to issue a class label parameters were detected, changes in glucose metabolism
warning to all protease inhibitors indicating that physicians
should closely monitor patients for hyperglycemia and dia-
betes mellitus potentially associated with their use.21 However,
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Copyright 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Insulin Resistance and Diabetes Mellitus with ART
the effect on glucose metabolism of individual protease
inhibitors varies dramatically and is best compared in studies
of HIV-seronegative individuals as these compounds can be
given alone in a very controlled environment, removing the
effects of other drugs and any contribution of the HIV
infection itself.
Murata et al22 demonstrated several years ago that the
protease inhibitors indinavir, ritonavir, and amprenavir directly
affect glucose uptake in 3T3-L1 adipocytes by selectively
inhibiting the transport function of Glut4. Indinavir and
ritonavir have been found to impair the activation of sterol
regulatory elementbinding protein 1 (SREBP-1) in adipose
and hepatic cells, resulting in abnormal intranuclear accumu-
lation of this protein and a later dysregulation of adipocyte
differentiation, glucose, and lipid metabolism.23,24 Additional
support for this effect has been demonstrated by a reduced
expression of peroxisome proliferatoractivated receptor-g
(PPAR-g), which is activated by SREBP-1 and a decreased
expression of PPAR-g-dependent adipocytokines and insulin-
signaling molecules in fatty tissues of protease inhibitor
treated patients compared with HIV-seronegative controls.25
Nelfinavir has been shown to reduce active SREBP-1 in the
nucleus and the levels of receptors for low-density lipoprotein
(LDL) and LDL receptorrelated protein that are intrinsic to
lipoprotein catabolism and vessel wall maintenance, suggest-
ing this as the mechanism for promotion of hypercholester-
olemia by this drug.26
Among the protease inhibitors, indinavir has been asso-
ciated with rapid and dramatic effects on glucose metabolism.
A single dose of indinavir given to healthy, HIV-seronegative
volunteers led to a significant decrease in insulin-mediated
glucose disposal, a very sensitive marker of insulin resistance.27
The administration of indinavir to healthy HIV-seronegative
volunteers for a period of 4 weeks also was associated with the
development of insulin resistance that was independent of any
changes in body composition.28
Data on the effects of nelfinavir on insulin resistance are
more limited because no studies have administered this drug
to healthy volunteers in the absence of other drugs or factors.
In the AIDS Clinical Trials Group Study 5005,29 the admin-
istration of nelfinavir was not associated with changes in the
reciprocal index of homeostasis model assessmentinsulin
resistance (HOMA-IR), which is derived from fasting plasma
glucose (FPG) and insulin levels (surrogate markers for insulin
resistance).30
Unboosted amprenavir had very modest effects on
glucose metabolism in a cohort of 14 HIV-infected individuals
initiated on antiretroviral treatment.31 In a large randomized
study of ritonavir-boosted fosamprenavir (the prodrug of
amprenavir), abnormalities in glucose levels were experienced
by approximately 1% of the patient population.32 In treatment-
naive patients, a favorable lipid profile is generally seen for
fosamprenavir.33
In a study of lopinavir/ritonavir administered for 4
weeks to HIV-negative men, although clear changes in lipid
were not induced, as measured by hyperinsulinemic clamp.34
However, in a larger study, 10 days of treatment with
lopinavir/ritonavir was associated with increases in HOMA-IR
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Tebas J Acquir Immune Defic Syndr  Volume 49, Supplement 2, September 1, 2008
and a 25% decrease in insulin sensitivity in healthy HIV-
negative volunteers,35 suggesting that this combination may
have some effect on glucose metabolism, albeit more modest
than those of indinavir.
Atazanavir has the reputation of being the most lipid
neutral of the protease inhibitors. Atazanavir did not induce
insulin resistance after 5 days of administration to healthy
HIV-negative volunteers.36 Ritonavir-boosted atazanavir, the
most common method of using atazanavir, was not associated
with significant changes in insulin sensitivity after 10 days of
administration to healthy HIV-negative adults.35 In a large study
of atazanavir in HIV-infected individuals, no changes in glucose
or insulin were detected after 48 weeks of administration.37
In a recently completed trial of HIV-infected, antiretroviral-
naive individuals, saquinavir was not associated with changes
in glucose disposal measured by clamps, although the small
sample size of the study (16 patients) may have limited the
ability of investigators to detect small changes.38
The effects of darunavir on metabolic parameters were
similar to those of boosted atazanavir in a 28-day study of
49 healthy volunteers, which did not include intensive clamp
measurments,39 demonstrating that this newer protease in-
hibitor is among those with fewer adverse effects on the
metabolic profile.
Data on the glucose effects of tipranavir are more
limited. In a recent study of 140 HIV-positive, antiretroviral-naive
individuals comparing tipranavir/ritonavir with lopinavir/ritonavir,
the effects of both combinations were similar on glucose
metabolism and other metabolic parameters and dependent on
the dose of ritonavir administered (100 vs. 200 mg).40
Nucleoside Analogs
Evidence generally suggests that nucleoside analogs
exert their effects on glucose metabolism indirectly, through
changes in body composition and mitochondrial toxicity.19
However, a recent study showed that stavudine, administered
for 4 weeks to healthy volunteers, was associated with modest
decreases in glucose disposal ratio as measured by hyper-
insulinemic euglycemic clamp when compared with placebo.
This suggests that the effects of nucleoside analogs may be
more direct than previously thought. However, these acute
changes in glucose disposal were small.41
Other Antiretrovirals
Two of the newer antiretroviral drug classes, chemokine
receptor 5 (CCR5) antagonists and integrase inhibitors, seem
to have a more favorable metabolic profile than their pre-
decessors. Preliminary reports from the large pivotal trials
MOTIVATE and BENCHMRK suggest that maraviroc and
raltegravir are not associated with any significant metabolic
effects.4244 Further studies are needed to confirm these data.
OTHER CONTRIBUTORS TO INSULIN
RESISTANCE IN HIV-INFECTED INDIVIDUALS
Comorbid Hepatitis C Virus Infection
Hepatitis C virus (HCV) infection has also been
associated with insulin resistance.45 The data are compelling
that this is also true in HIV-infected patients coinfected with
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HCV. In a large cross-sectional study, the association between
HCV and diabetes in HIV-infected individuals remained
significant after adjusting for body mass index and family
history of diabetes (odds ratio = 3.7, 95% confidence interval:
1.3 to 11.1, P = 0.02).46 In patients coinfected with HCV/HIV,
increased insulin resistance, higher rates of diabetes, and lower
low-density lipoprotein cholesterol (LDL-C) values were seen
versus those without HCV after initiation of ART using NRTI
treatment regimens with and without nonnucleoside reverse
transcriptase inhibitors (NNRTIs).47 Thus, HIV/HCV coin-
fected individuals are at a higher risk of developing insulin
resistance and diabetes while on treatment, warranting close
monitoring of these patients.
Nonantiretroviral Drugs
Drugs used for the management of complications of
HIV infection may be associated with worsening insulin
resistance or diabetes; these agents include niacin for the
treatment of hyperlipidemia,48 steroids for the management of
some comorbid infections or immune reconstitution syn-
drome, and thiazides for the management of hypertension.
These drugs should be used with caution or alternatives con-
sidered for HIV-infected patients at high risk for developing
diabetes.
MANAGING DIABETES IN PATIENTS WITH
HIV INFECTION
Patients with HIV infection are more likely to develop
diabetes mellitus than the general population19; data from the
Multicenter AIDS Cohort Study (MACS) population indicate
a relative risk as high as 4 for the development of this
condition.12 The care of patients with diabetes is complex and
often requires a multidisciplinary team approach that includes
physicians, nurse practitioners, nurses, nutritionists, and
pharmacists.7 Many HIV treatment providers are also the
primary care providers for their patients whereas others are
providing only specialty care. This is an important consider-
ation when managing a long-term disease like diabetes; if
a clinical practice is not providing primary care to the HIV-
infected patient, then the practice should ensure that diabetes is
managed effectively elsewhere.
DiabetesEstablishing the Diagnosis
According to ADA guidelines,7 an individual with an
FPG level of at least 126 mg/dL has diabetes and an individual
with an FPG between 110 and 125 mg/dL has impaired fasting
glucose (IFG) (Table 1). The oral glucose tolerance test,
although more sensitive and specific than FPG, is not
recommended for routine clinical use but may be required
for the diagnosis of diabetes in some patients with IFG or in
women with gestational diabetes.7
Measurement of FPG levels is the preferred test to
diagnose diabetes and IFG in children and nonpregnant adults.
Unless the patient has unequivocal hyperglycemia, an
abnormal test should be confirmed by repeat testing on
a different day.7 As HIV-positive patients are at high risk for
the development of insulin resistance and diabetes, this test
should be repeated periodically, as often as yearly, especially
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J Acquir Immune Defic Syndr  Volume 49, Supplement 2, September 1, 2008 Insulin Resistance and Diabetes Mellitus with ART

TABLE 1. Definitions of Abnormal Glucose Metabolism7

Fasting After OGTT (75-g Glucose Load) Comments
Normal ,100 mg/dL ,140 mg/dL Fasting defined as $8 h from last meal
Prediabetes IFG: 100125 mg/dL Impaired glucose tolerance:
2-h postglucose 140199 mg/dL
Diabetes mellitus Fasting glucose $126 mg/dL 2-h postglucose $200 mg/dL Symptoms (polyuria, polydipsia, and weight loss)
and a casual glucose of $200 mg/dL is
diagnostic of diabetes
OGTT, oral glucose tolerance test.

among individuals with other genetic predispositions to
diabetes and those with high cardiovascular risk or obesity.18
Individuals with IFG and diabetes are at higher
cardiovascular risk; diabetes is a cardiovascular risk equivalent
that modifies goals for lipids and blood pressure.49 The goal
of treatment is to improve glycemic control and to maintain
glycosylated hemoglobin (Hb A1C) levels below 7%.7 Aggres-
sive targets for blood pressure (,130/80 mm Hg) and lipid
levels should be established (LDL-C ,100 mg/dL). Tri-
glyceride and HDL levels also may be targeted49 but reaching
these goals may be very difficult in this population. Low-dose
aspirin should be considered for all patients.
In patients with IFG or established diabetes, a medical
history should be taken that evaluates the individual for the
presence of diabetic complications such as retinopathy,
nephropathy, neuropathy, cardiovascular disease, peripheral
vascular disease, sexual dysfunction, and gastroparesis. The
physical examination should include blood pressure testing,
fundoscopy, thyroid palpation, evaluation of the skin, testing
for evidence of neuropathy, and palpation of distant pulses.7
The laboratory workup should include measurements of
Hb A1C, fasting lipids, liver function, microalbuminuria,
creatinine clearance calculation, and thyroid-stimulating
hormone. Appropriate referrals should be made to ophthal-
mologists, family planners, and diabetes educators.7
MANAGING DIABETES IN THE
HIV-INFECTED PATIENT
Optimization of HIV Treatment Regimens in
Patients With Diabetes
If an HIV-positive patient has diabetes or is at high risk
for it, then consideration should be given to initiation of an
HIV treatment regimen less associated with the development
of this complication. Individual protease inhibitors most
associated with development of insulin resistance should be
avoided. If IFG or diabetes has occurred while on therapy, then
the substitution of one or several of the components of the
antiretroviral regimen with another agent that is less associated
with this particular metabolic complication is reasonable. For
example, if the patient is receiving indinavir, then a consid-
eration should be made to substitute it (if possible, based on
antiretroviral history and resistance testing) with an NNRTI,
another protease inhibitor less associated with insulin re-
sistance, or a drug from one of the new drug classes (CCR5
antagonists or integrase inhibitors), even though data are
limited for these new agents, and it might not be possible to
evaluate the tropism of the virus in an individual with well-
controlled viral replication. Although switch studies have
demonstrated significant reductions in lipid levels, their benefit
has been more limited in improving glucose parameters.50
Lifestyle Change-Based Interventions
At the present time, overweight and obese individuals
constitute a much larger segment of the HIV-infected
population than patients with wasting syndrome.51 As with
individuals in the general population, an obese patient with
HIV should be advised about the benefits of weight loss and
regular physical activity; this is applicable not only to patients
with high risk of diabetes but also to individuals who have
already developed IFG or frank diabetes. There is considerable
evidence that lifestyle changes, including changes in diet (eg,
calorie restriction and reduction in intake of carbohydrates,
saturated fats, and cholesterol) and increased physical activity
can help reverse the progression to type 2 diabetes and
improve glycemic control in individuals already diagnosed
with the condition.7,5254 In a randomized study, aggressive
lifestyle modification was more effective than metformin in
preventing the development of diabetes in individuals with
elevated fasting glucose55; however, adherence to lifestyle
changes is difficult to maintain over time. The expected
improvement in Hb A1C levels in individuals who are able to
follow lifestyle modification recommendations is 1%2%,
similar to goals that are attainable with some drug regimens.
Pharmacologic Treatment of Diabetes
A detailed discussion of the management of patients
with diabetes is beyond the scope of this review. The ADA
periodically updates its recommendations for the management
of individuals with glucose metabolism impairments,7 and the
same standards of care used in the general population should
be applied to patients with HIV infection.
If modification of a patients lifestyle is not successful
for reaching Hb A1C goals, then metformin should be
considered as first-line therapy,7,56 particularly in patients with
visceral obesity. Metformin has been used in patients with HIV
infection and was particularly effective in a small cohort of
individuals with abdominal obesity.57,58 However, metformin
should be used with caution in patients with renal failure or
history of lactic acidosis. Because the use of this drug is
associated with weight loss,56 its use in HIV-infected patients
might exacerbate lipoatrophy. Usually a low metformin dosage
of 500 mg twice a day is initiated and, if needed, gradually

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Tebas J Acquir Immune Defic Syndr  Volume 49, Supplement 2, September 1, 2008
increased to the maximum tolerated dose of 23 g daily.
The expected improvement in Hb A1C levels with the use
of metformin is 1.5%.59 Thiazolidinediones (including the
glitazones rosiglitazone and pioglitazone) can be added to
the treatment regimen if Hb A1C goals are not reached or they
can be used as first-line therapy if the patient has significant
lipoatrophy. In a study of HIV-infected patients with hyper-
insulinemia and increased waist-hip ratio, combination therapy
with metformin and rosiglitazone was not much better at
reversing lipoatrophy than either drug alone.58 Rosiglitazone
was associated with improved insulin resistance when eval-
uated in small or uncontrolled trials for the management of
lipoatrophy60; however, these results were not seen in a large,
properly powered study.61 Rosiglitazone negatively affects
lipid profiles by increasing LDL-C and decreasing HDL-C,58
which can be problematic in some patients and may be one of
the contributors to the increased frequency of cardiovascular
events associated with its use.62 The role of rosiglitazone
in the management of diabetes is currently in flux due to
the increased risk of cardiovascular events associated with
its use62,63a concern that has become generalized to the
thiazolidinedione class. In addition, both rosiglitazone and
pioglitazone now carry black box warnings indicating that the
thiazolidinediones may cause or exacerbate congestive heart
failure in some patients.64 The data for pioglitazone are some-
what more positive; along with exercise, this agent produced
small improvements in extremity fat in HIV-positive individ-
uals with lipoatrophy.65 Glitazones have to be used with
caution (or not at all) in patients with significant liver and/or
cardiovascular disease. In HIV-positive individuals, if the
use of this class of drugs is considered, then pioglitazone
should be the first choice; the usual dose is 1545 mg daily.64
The expected improvement of Hb A1C levels with its use is
approximately 1%.59
The data for other antidiabetic drugs (eg, glinides,
sulfonylureas, exenatide, and alpha-glucosidase inhibitors) in
HIV-infected individuals are very limited. Combination therapy
can be considered for individuals who have not reached
treatment goals with the use of metformin or pioglitazone. The
patient who does not reach targets with oral treatments should
be initiated on insulin, which is usually started with a long-
acting preparation at bedtime with slow dosage increases
dependent on the results of glucose level self-monitoring; oral
agents can be continued. Referral to a practice with expertise
in the management of diabetes and its complications should be
considered if these strategies fail to achieve adequate control.
SUMMARY
Physicians who treat HIV-infected patients must con-
sider a number of factors when deciding on the best
therapeutic strategy for an individual. These include deter-
mination of a patients metabolic status before initiation of
HAART and continued monitoring of development of meta-
bolic abnormalities during antiretroviral treatment. In patients
at high risk for development of the metabolic syndrome or
diabetes, antiretroviral drug therapies can be designed to
minimize metabolic effects. The HIV caregiver, whose
primary area of expertise may be infectious diseases, is also
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Copyright 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
often called upon to treat the metabolic syndrome or diabetes
in their patients or be able to recognize these disorders for
patient referral to an appropriate expert. In either circum-
stance, keeping informed of the metabolic risks and latest
standards of care for metabolic syndrome and diabetes is
essential to maximizing care of the HIV-infected patient.
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