Mallon_edit.qxp 16/7/08 10:32 am Page 16
HIV and AIDS
required. When lipid-lowering drugs are necessary (i.e. when receiving HAART,
110,111
although normalisation of triglyceride levels is
cardiovascular risk is sufficiently high, as determined from risk factor infrequent.
111
Co-administration with ritonavir and nelfinavir may
charts, for example), statins are a suitable first-line therapy for primary compromise the efficacy of fibrates.
57
Niacin has the propensity to
hypercholesterolaemia, whereas fibrates should be restricted to those exacerbate hyperglycaemia, with seven of 11 HIV-infected subjects in
with significant hypertriglyceridaemia.
96,97
Statins and fibrates appear one study developing insulin resistance, and offers only a slight increase
to have only moderate lipid-lowering efficacy in HIV-infected patients in HDL cholesterol levels in this population.
112
with dyslipidaemia,
98–103
and appropriate cholesterol target levels may
be more difficult to achieve than in the HIV-negative population.
104
Lifestyle Modification
The value of adding fibrates or other lipid-lowering agents to statin Alterations to lifestyle factors that are amenable to change, such as
therapy is largely unproven in HIV-infected subjects (as is the case in cessation of cigarette smoking, increasing physical activity, improving
the non-HIV-infected population), and the NCEP III guidelines limit dietary habits and controlling hypertension, should be undertaken
treatment recommendations to monotherapy.
57
Initial evidence where possible to reduce cardiovascular risk. Dietary counselling when
suggests that combination statin plus fibrate
101,102
and statin plus used in conjunction with exercise was shown to be effective in reducing
ezetimibe
105
therapy provides greater improvement in individual lipid cholesterol levels in one study, although it proved difficult to
parameters than statin monotherapy in HIV-infected patients. implement and to maintain long-term adherence,
113
but offered no
Nevertheless, only a minority of patients with dyslipidaemia are likely benefit in another study.
114
Dietary counselling should focus on
to achieve all NCEP III targets for lipid levels with dual statin plus reducing saturated fat and cholesterol intake and promoting the
fibrate therapy.
101,102
Currently, the most effective statin on the market consumption of fruit, vegetables and fibre-rich foods.
95
Exercise has
with regard to LDL cholesterol lowering is rosuvastatin, and in HIV- been shown to reduce plasma triglyceride levels
115
and blood
infected individuals data would be useful since rosuvastatin could pressure.
116
Exercise promotion should emphasise the benefits of
potentially allow many more patients to achieve target lipid levels. regular moderate-intensity exercise in achieving cardiovascular fitness.
95
Obese patients should be encouraged to lose weight, since even a
Which Lipid-lowering Agents to Use? modest reduction in bodyweight is likely to improve associated
In view of the potential for drug interactions, care should be taken in the components of the metabolic syndrome, including dyslipidaemia,
choice of lipid-lowering therapy in patients on HAART. In common with glucose intolerance and hypertension.
117
In reality, sustained weight
PIs, many statins are metabolised by the hepatic microsomal cytochrome loss is difficult for many to achieve and, rather than advocating
(CYP) P450 system, thereby creating potential for drug interaction in the weight-loss diets, most patients should be encouraged to make small-
HIV-infected patient. Statins that may be used in patients receiving PI scale dietary improvements that are sustainable in the context of their
therapy include pravastatin (although it has a more modest LDL- lives rather than attempt more ambitious changes.
cholesterol-lowering effect than other commonly used statins),
atorvastatin (with close monitoring), fluvastatin and rosuvastatin;
95
Smoking rates among HIV-infected individuals are reported to be as
simvastatin and lovastatin are contraindicated.
57,106
Switching to high as 60%,
25,118
which makes smoking a substantial modifiable
atazanavir is an alternative, because this newer PI does not appear to be cardiovascular risk factor in this population. Smoking cessation is
associated with the same degree of dyslipidaemia.
107
Of the NNRTIs, probably more important in the HIV-infected population than in the
delaviradine is an inhibitor of CYP3A4, and its use carries the same general population because many of the cardiovascular risks associated
constraints in relation to statin co-administration.
57
Efavirenz is a mixed with HIV/HAART are exacerbated by smoking.
118
As such, smoking
inducer and inhibitor of CYP3A4, with an overall induction effect, but cessation should be a major focus of attention for reducing
there are limited quantitative data on the efavirenz–statin interaction. cardiovascular risk.
Ezetimibe, which inhibits intestinal uptake of dietary cholesterol, is not an
inhibitor of CYP3A4 and shows no pharmacokinetic interaction with PIs HIV-infected patients are at higher risk of developing hypertension than
or NNRTIs.
105
the general population,
119
with one case-control study reporting a
prevalence of 34% among HIV-infected patients (median age 41 years)
It is unclear whether hypertriglyceridaemia is a true causal on HAART compared with 12% among age-matched non-HIV-infected
cardiovascular risk factor that can be modified with treatment or merely controls.
120
Elevated blood pressure in the HIV-infected patient appears
a biomarker of future risk. Triglyceride reduction is associated with less to be related to the presence of established risk factors, including
frequent recurrence of coronary events among patients with antiretroviral-induced central fat gain and metabolic disorders, in
established ischaemic heart disease,
108
but it is unclear whether this particular hypertriglyceridaemia and insulin resistance.
120,121
In treating
effect is independent of improvement in other lipid parameters or uncomplicated hypertension in this setting, the preferred first-line
whether it applies to primary prevention. A recent meta-analysis agent is an angiotensin-converting enzyme inhibitor/angiotensin II
showed that fibrate use was associated with a reduction in incidence of receptor blocker or thiazide diuretic (first choice) or amlodipine (second
non-fatal myocardial infarction; however, it had less favourable effects choice).
95
It should be noted that β-blockers and non-thiazide diuretics
on other end-points, including a tendency towards a higher all-cause are liable to worsen the metabolic profile, while calcium channel
mortality rate.
109
The NCEP guidelines identify a role for triglyceride blockers have the potential for pharmacokinetic interactions with PIs.
control in the management of dyslipidaemia,
57
although it is not a
primary treatment goal and, as noted above, the evidence base for Case Examples of Cardiovascular Risk Screening –
fibrates is far less impressive than for statins. Of the available More than Simply Measuring Cholesterol
triglyceride-lowering agents, the fibrates bezafibrate, fenofibrate and A basic principle of primary prevention is that the intensity of risk-
gemfibrozil improve atherogenic profile in HIV-infected patients reduction interventions should be adjusted to the individual’s absolute
16 EUROPEAN INFECTIOUS DISEASE
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