Cardiovascular Risk Factors and Metabolic Complications in HIV-Infected Patients Receiving HAART
February 3, 2006
Metabolic and morphological changes, collectively referred to as lipodystrophy, are prevalent among HIV-infected individuals treated with antiretroviral therapy (ART). The morphological changes associated with lipodystrophy cannot only be highly stigmatizing, but the metabolic manifestations of lipodystrophy may contribute to a range of morbidities, most notably premature heart attacks and strokes. Moreover, patients who are anxious about developing lipodystrophy may risk HIV disease progression by delaying the commencement of therapy or by stopping ongoing therapy in an attempt to manage these issues. However, the incidence of these treatment-associated adverse changes may be minimized through prudent drug selection at treatment initiation and proactive treatment modification.
Lipodystrophy is typically characterized by some combination of the following symptoms and disorders in persons on ART:
Fat accumulation in the abdomen or viscera is commonly accompanied by insulin resistance, glucose intolerance and dyslipidemia -- a syndrome referred to as the metabolic syndrome or syndrome X. This syndrome is being diagnosed at increasing frequencies within general medical practice and is over-represented in populations experiencing cardiovascular disease (CVD).
Once established, the metabolic syndrome is a vicious cycle that is hard to break. Lipid accumulation in the liver, pancreas, skeletal muscle and visceral sites due to abnormal peripheral storage contributes to insulin resistance, thereby further exacerbating problems with peripheral lipid storage and glucose handling. Thus, avoiding the initial establishment of the syndrome may be particularly relevant for the control of this aspect of lipodystrophy.
A typical lipid profile in an HIV-infected individual on ART often includes a low HDL cholesterol level, elevations in total and low-density lipoprotein (LDL) cholesterol levels (particularly the high-risk LDL particles) and elevations in triglycerides, the combination of which puts the patient at high risk for future CVD. Insulin resistance is also a known risk factor for CVD, and diabetes mellitus is likewise considered to be a CVD risk equivalent according to National Cholesterol Education Program (NCEP) guidelines. Thus, the metabolic disturbances that accompany HIV infection and ART use are likely to have important consequences for future cardiovascular health.
In the HIV-uninfected population, CVD, which includes coronary heart disease, stroke, congestive cardiac failure and hypertensive disease, is the leading cause of death in both the United States and Europe. In 2002, CVD accounted for 38% and 49% of all deaths in these respective regions.1,2 A number of primary or traditional risk factors for CVD are well established, and several additional risk factors have been recently described. The primary risk factors for CVD include age, smoking, hypertension, elevated total and LDL cholesterol levels, diabetes mellitus, obesity and physical inactivity.
For HIV-infected patients receiving treatment with ART, the risk for CVD may be significantly greater than that for the general population3 and may increase with each year of ART exposure.4,5 Recent cohort and database studies suggest that cardiovascular events substantially contribute to mortality in HIV-infected patients receiving successful highly active antiretroviral therapy (HAART).6 Cardiovascular events are the underlying cause of more than 10% of deaths in this population,4,5 and CVD consistently ranks in the top four or five leading causes of death in persons with HIV (typically after AIDS-related events, end-stage liver disease and malignancy). The close relationship between HAART and CVD highlights the need for careful consideration of CVD risk in the long-term management of persons with HIV infection.
Factors associated with an increased risk of CVD development can be classified as modifiable and non-modifiable. Modifiable, traditional factors include smoking, elevated LDL and non-HDL cholesterol, being overweight, lacking exercise and factors comprising the metabolic syndrome (i.e., insulin resistance, elevated waist circumference, hypertension, elevated triglycerides and low HDL-cholesterol). Non-modifiable factors include age, sex and genetic predisposition.7,8 In addition, several emerging CVD risk factors have been identified in recent years, such as homocystinuria and elevated levels of C-reactive protein.7,8 The current data indicate that multiple risk factors for CVD may be unfavorably affected by HIV infection and components of HAART.
The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group conducted a prospective, observational study to examine the risk of myocardial infarction in HIV-infected patients receiving HAART.4,5 The study collected data on more than 23,000 patients, with a median age of 39 years, who were enrolled in 11 previously established cohorts in Europe, the United States and Australia. The patient population had a number of traditional cardiovascular risk factors at a high baseline prevalence, including dyslipidemia (42%), being a current smoker (47%), being a former smoker (16%), hypertension (5.6%), having a body mass index above 30 kg/m2 (4.7%) and diabetes mellitus (3.5%). Over a period of 1.6 years up through February 2002, 126 patients had a myocardial infarction (incidence: 3.5 events/1,000 person-years).
Additional follow-up through February 2004 showed that a total of 277 patients experienced a myocardial infarction.5 The authors observed an increased incidence of myocardial infarction with longer exposure to HAART during the first 7 years of use: After adjusting for potential confounding factors, there was a 17% relative increase in the rate of myocardial infarction per year of exposure to HAART. In addition to HAART exposure, other independent predictors of myocardial infarction included older age, status as a current or former smoker, male gender and previous CVD. The presence of elevated total cholesterol levels, elevated triglyceride levels and diabetes mellitus at baseline were also associated with an increased myocardial infarction risk.
Risk calculators, such as the Framingham risk-assessment tool, are typically used to assess the 10-year CVD risk in individuals in the general population who have two or more risk factors for CVD. It is standard practice to initiate some form of intervention when the 10-year Framingham risk exceeds 20%. Application of the Framingham tool to D:A:D patients consistently underestimated the number of events that actually occurred in this study.9 This may be because some key factors common in the D:A:D population, such as hypertriglyceridemia or insulin resistance, are not used in the Framingham calculations or because there are direct effects of HIV and ART on risk that are not captured in the calculations. These data suggest that lower 10-year CVD risk calculations should be used to guide CVD interventions among HIV-treated patients than those used for the general population. Future prospective studies testing this hypothesis though will be needed to clarify whether such a strategy is effective for all HIV-infected patients.
It is clear that CVD risk reduction needs to be actively addressed in persons with HIV infection. Because the impact of any CVD intervention has a lag time -- that is, the benefits accrue over several years -- the earlier that CVD risk can be identified and interventions introduced, the sooner the risk can be managed. It is important to consider, however, that risk reduction is relative rather than absolute. Thus, interventions implemented now in the HIV population will only serve to slow the trajectory of a potential CVD "epidemic" among an aging population of HIV-infected persons, and the benefits for each individual cannot be clearly measured.
Managing CVD risk involves assessing all potential CVD risk factors such as dyslipidemia, insulin resistance, hypertension, lack of exercise and being overweight.10 In the setting of HIV infection, many of the interventions for reducing the risk of CVD are comparable to those recommended for the general population. Therapeutic lifestyle changes -- namely, smoking cessation; adherence to a Mediterranean diet high in omega-3 fats, low in total and saturated fats, and high in fiber and fresh fruits and vegetables; and regular exercise -- comprise the basic initial intervention. A review of the available evidence shows that individuals with coronary heart disease who modify their diet reduce their risk of CVD and "all cause" morbidity and mortality.11,12
Pharmacological interventions with lipid-lowering drugs may be considered for patients with dyslipidemia. More specifically, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) and brush border inhibitors (e.g., ezetimibe [Zetia]) are the most effective for treating hypercholesterolemia, while fibric acid derivatives (i.e., fibrates) are more effective for treating hypertriglyceridemia and raising HDL levels. The NCEP Adult Treatment Panel (ATP) III guidelines provide direction for managing dyslipidemia, with targets adjusted according to risk.13 Patients should be monitored during the use of statins, as the potential for drugs interactions, particularly between protease inhibitors (PIs) and statins, may increase the risk of toxicity.14
Statins and fibrates appear to influence lipid levels similarly, though to varying degrees, in HIV-infected individuals and in individuals within the general population. There is insufficient investigation of other pleiotropic effects of statins, such as on vascular tone, to assess whether these effects are similarly preserved. Treatment with statins and fibrates rarely achieves NCEP-defined targets in HIV-infected patients, so combinations of agents may often be required.
For example, a recent retrospective, matched-cohort analysis of 53 ART-treated HIV-infected U.S. military veterans and 53 HIV-uninfected veterans, all with dyslipidemia (total cholesterol or triglycerides greater than 200 mg/dL) and all initiating lipid-lowering therapy, indicated that HIV-infected individuals were less likely to achieve NCEP targets.15 The cohorts were mostly non-white (51%) and male (95%) with a mean age of 47 years and more than two risk factors for CVD. Compared to the HIV-infected group, the HIV-uninfected patients were more likely to achieve a total cholesterol level less than 200 mg/dL at 3 months (odds ratio [OR] = 4.57; P = .031) and 6 months (OR = 3.75; P = .013) and triglyceride levels less than 200 mg/dL at 6 months (OR = 5.4; P = .033). Only 28% of the HIV-infected veterans met NCEP targets for total cholesterol at 6 months compared with 61% of the HIV-uninfected veterans.
The outcome differences between HIV-uninfected veterans and HIV-infected, ART-treated veterans arise for two main reasons. First, pravastatin (Pravachol, Pravigard), a relatively less potent statin agent, was more often administered to HIV-infected individuals, whereas simvastatin (Vytorin, Zocor) was used more commonly in the HIV-uninfected veterans. Simvastatin is generally contraindicated in individuals on HAART due to drug interactions that may dangerously increase exposure to this agent. Second, the individuals with HIV infection tended to have relatively more severe dyslipidemia than the HIV-uninfected individuals. Hence, even if given the same treatment, the HIV-infected individuals were less likely to reach the NCEP target values even if the drug effect on reducing cholesterol was the same. Thus, more than one intervention (e.g., therapy switch, one or more lipid-lowering agents) may be needed for HIV-infected individuals on HAART to meet NCEP targets.
In a study involving 22 individuals with an LDL cholesterol level above 130 mg/dL and triglycerides below 350 mg/dL despite 20 mg/day of pravastatin, the addition of ezetimibe led to declines over 24 weeks in total cholesterol (234 to 207 mg/dL) and LDL cholesterol (146 to 123 mg/dL) but did not affect HDL cholesterol (52 to 53 mg/dL).17 Lopinavir/ritonavir (LPV/r, Kaletra) levels, tested in six individuals, did not change as a result of adding ezetimibe. The effects of ezetimibe observed here are consistent with those observed in the general population. The data suggest that ezetimibe is a suitable adjunct to statin treatment in persons with HIV and hyper(LDL)cholesteremia who have not reached appropriate NCEP targets after therapeutic lifestyle changes, treatment switching (when feasible) or statin therapy.
Previous studies have indicated that fibrate drugs also have similar effects on triglycerides and HDL cholesterol among HIV-infected and HIV-uninfected individuals. Niacin (Advicor, Niacor, Niaspan) and fish oils are suitable alternative treatments for elevated triglyceride levels.10,14,18 Niacin derivatives may be associated with an increase in insulin resistance and hence may not be suitable for many individuals with HIV infection on ART. The insulin sensitizing agent metformin (Glucophage, Fortamet) may lead to modest improvements in triglycerides and may improve some other aspects of the metabolic syndrome in individuals with demonstrable insulin resistance. Rosiglitazone (Avandia), a peroxisome proliferator-activated receptor-γ agonist, does not substantially affect limb fat mass when given to individuals with lipoatrophy but may improve insulin resistance and reduce liver fat content. In general, studies involving rosiglitazone in the setting of HIV reveal that the agent modestly aggravates lipid profiles.19,20
In terms of managing lipoatrophy in persons receiving treatment with a thymidine analog, more recent investigation of the nutritional supplement uridine in a very small study suggests that this agent is worthy of further investigation.21 However, a lack of information on drug interactions and the observation of a small, but significant, decline in HDL cholesterol suggest that clinicians should await data from a more comprehensive study before considering uridine as a treatment option for morphological change.
Studies with recombinant human growth hormone suggest that this also may be a potentially useful intervention in individuals with fat accumulation and the metabolic syndrome.22 Treatment with growth hormone leads to a decline in visceral fat and a modest improvement in lipid profile. Over the short term, growth hormone may cause a modest and transient worsening of insulin resistance and is therefore contraindicated in individuals with diabetes mellitus.
The management of insulin resistance remains unclear. Although evidence exists to indicate that insulin resistance is an independent risk factor for CVD and a harbinger of future glucose intolerance and diabetes mellitus, the necessity of managing insulin resistance remains a topic of debate among endocrinologists. In the setting of HIV infection, insulin resistance is not only associated with some medications, but, as in the general population, it is also associated with visceral adiposity and the metabolic syndrome.
Recently, a small, randomized study of rosiglitazone (8 mg/day) and metformin (2 g/day) for the treatment of HIV lipodystrophy was reported.23 Thirty-nine male patients with clinical lipodystrophy were randomized to either rosiglitazone (n = 19) or metformin (n = 20) for 26 weeks. Compared with metformin, rosiglitazone significantly increased subcutaneous abdominal fat, but rosiglitazone also increased visceral abdominal fat. The area under the curve for insulin after an oral glucose tolerance test decreased similarly with both agents. Adiponectin, an insulin-sensitizing hormone, markedly increased with rosiglitazone, but not with metformin. The clinical significance of this observation is not clear at this time. However, metformin showed greater benefits for fasting lipid profiles than rosiglitazone. Flow-mediated vasodilation (vascular reactivity) also increased significantly with metformin (mean difference: 1.5%, 95% confidence interval: 0.4%-3.3%; P = .03), but not with rosiglitazone.
Although the effects of both agents on insulin resistance were similar, these data suggest that metformin can improve visceral adiposity, fasting lipid profiles and vascular reactivity more so than rosiglitazone. The observations were consistent with previous studies of metformin. In addition, previous data have suggested that the metabolic benefits of metformin are enhanced by exercise.24
The initiation of ART generally leads to changes in lipids. These effects include a rise in total cholesterol and both HDL and LDL cholesterol. Some physicians attribute these rises to the correction of lipid abnormalities associated with HIV progression. However, the changes in total and LDL cholesterol typically increase to values well above pre-morbid levels.25 Studies in healthy volunteers suggest that individual antiretroviral agents can raise lipids. This observation is most well recognized with ritonavir.26 Recent data suggest that modest, but statistically significant, differences in changes in lipids and glucose disposal occur when healthy volunteers are given lopinavir/ritonavir three capsules 400/100 mg twice daily versus atazanavir 300 mg + ritonavir 100 mg once daily.27 Lopinavir/ritonavir resulted in greater declines in glucose disposal and greater increases in triglycerides. The observed changes in HDL cholesterol were identical for the two PI regimens.
During initial therapy for persons with HIV infection, both atazanavir28 and lopinavir/ritonavir29 are associated with modest, but sustained, increases in HDL cholesterol. Monte Carlo simulations based on lipid data derived from a comparative study of first-line atazanavir versus nelfinavir (NFV, Viracept) suggest that the differences in lipid profiles of these agents, when applied to a large population (a population size of 5,000 was used for the models), are likely to be important for future cardiovascular risk.30 In the simulations, atazanavir-treated individuals, regardless of the absence or inclusion of other CVD risk factors (e.g., smoking, diabetes mellitus, hypertension), had significantly lower (P < .001) 10-year Framingham risks than nelfinavir-treated individuals (see table). These data, when considered in the setting of a large HIV population followed over a prolonged period of time, suggest that the modest differences in lipid profiles between atazanavir and nelfinavir, and potentially applicable across other comparative PI studies, are likely to be clinically relevant and will influence the magnitude of a future CVD epidemic in persons on ART. Whether these comparative simulations hold up with the more often prescribed ritonavir-"boosted" atazanavir remains to be seen.
The relative impact of different ART combinations on insulin sensitivity and glucose handling has not been extensively studied in persons with HIV infection. Available data suggest a role for stavudine33 and several PIs, most notably indinavir (IDV, Crixivan). In healthy volunteers, indinavir, ritonavir, indinavir + ritonavir and lopinavir/ritonavir, but not atazanavir or amprenavir (APV, Agenerase), have some impact on glucose disposal.10,14 The effects of atazanavir + ritonavir are modest and intermediate to placebo and lopinavir/ritonavir.27 Along with antiretroviral choice, recent cohort data suggest that hepatitis C coinfection may be a specific risk factor for insulin resistance during therapy.36
Although therapeutic lifestyle changes comprise the preferred initial approach to CVD risk management for individuals on established ART, treatment guidelines10,14 and some available clinical trials data37,38 suggest that switching certain antiretroviral drugs to agents with better lipid profiles, when feasible, can meet NCEP targets without the (immediate) need for further interventions (e.g., statins) or can improve the chance of meeting target levels in conjunction with another intervention. For patients with available ART options, selecting an agent with a lower potential to induce metabolic abnormalities may be considered. For highly treatment-experienced patients who have limited therapeutic options, the risk of virological or immunological failure and its associated morbidity and mortality must be weighed against the benefit of reducing a relatively "rare" acute coronary event in the distant future.
Most previous studies of dyslipidemic individuals receiving a boosted or unboosted PI have focused on switching to an alternative drug class, such as a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an all-NRTI regimen like zidovudine/lamivudine/abacavir (AZT/3TC/ABC, Trizivir). Replacement of a PI with an NNRTI or abacavir has been shown to help manage lipid abnormalities.39 In the recent past, this has been the preferred tactic for individuals who initiated a PI-based regimen and who still had the NNRTI option available. These switches generally lead to a range of metabolic benefits, which include declines in total and LDL cholesterol and triglycerides and an increase in HDL cholesterol. The switch to an NNRTI may also improve the profile of lipid subfractions. One recent study showed that the proportion of small-particle LDL, the most proatherogenic LDL, declined after patients switched to efavirenz, although the clinical relevance of this finding is uncertain.38
Given the approval of atazanavir, a once-daily PI with a low pill burden and an attractive lipid profile, the option of switching within the PI class now exists. Switching from a boosted or unboosted PI to atazanavir has been associated with lipid benefits, particularly with regard to triglyceride and total and LDL cholesterol levels.38 Improvements in total cholesterol with this switch often exceed 15% -- an effect similar to that achieved with pravastatin. It should be noted that the effects of the more commonly used boosted atazanavir as a replacement for an alternative boosted PI are less well established and remain under study.
The largest study to investigate drug switching within the PI class is the SWAN study.38 This was a comparative, multicenter, open-label, randomized study in which 407 individuals receiving successful treatment with a twice-daily, PI-based regimen and with a viral load less than 50 copies/mL were randomized 2:1 to either replace their PI with an atazanavir-containing regimen (n = 274) or continue on their current PI (n = 133). Participants were excluded if they previously failed a PI-based regimen or demonstrated PI resistance. Unboosted atazanavir was dosed at 400 mg once daily for all individuals except for those receiving tenofovir (9% of all individuals), in which case the boosted dose of atazanavir 300 mg + ritonavir 100 mg once daily was used. A total of 54% of individuals entering the study were on a ritonavir-boosted PI regimen, with 37% of the total receiving lopinavir/ritonavir. On average, participants had been receiving a PI for 40.3 months. The primary study endpoint was virological failure, defined as a rebound in HIV-1 RNA above 50 copies/mL.
Viral rebound was observed in 7% of individuals who switched to atazanavir compared with 16% in the continuation group (P < .01).38 This difference was largely driven by the subset of individuals who were receiving an unboosted PI at baseline.
Treatment failure (including virological failure and all other reasons for discontinuation) was reported in 21% of individuals who switched and in 34% of individuals who maintained their current PI (P < .01). With regard to adverse events, gastrointestinal symptoms were reported in 8% of individuals switching to atazanavir but in 13% of controls, and significantly fewer atazanavir recipients required anti-diarrheals during the study (P < .05). Only 6% of individuals in each group discontinued due to adverse events. The discontinuation rate for scleral icterus in the atazanavir arm was 1%.
Consistent with previous studies, switching to atazanavir resulted in marked improvements in a number of lipid parameters.38 Most notably, non-HDL cholesterol declined by 18% with the switch to atazanavir compared with a decrease of 3% in those individuals who continued on their original PI (P < .0001). This resulted in a higher proportion of atazanavir recipients meeting NCEP target values for multiple lipid parameters as compared with those who continued treatment with their original PI.
These data suggest that individuals receiving a boosted or unboosted PI who have not previously failed PI therapy could consider modifying their treatment regimen by switching to an atazanavir-based combination as a means of reducing their pill burden and improving their lipid profile. The choice of boosted or unboosted atazanavir appears to depend on the agents to be co-administered with atazanavir: When tenofovir is currently being used, it is obligatory to use boosted atazanavir; in other circumstances, boosting does not appear to be required. The applicability of this approach to individuals who have experienced prior failure or resistance to PIs has not been evaluated.
Lipid parameters improved when switching to tenofovir but were unchanged after switching to abacavir.40 Mean changes in total cholesterol (P = .003) and LDL cholesterol (P = .04) significantly favored tenofovir relative to abacavir.
Lipid parameters were generally higher in persons receiving stavudine at baseline. The median total cholesterol level declined over 48 weeks for those receiving stavudine at entry and who then switched to tenofovir (from 5.9 to 5.5 mmol/L), while no change was seen in those switching to abacavir (5.4 mmol/L at both times). For individuals receiving zidovudine at entry, small rises in median total cholesterol were observed (tenofovir: from 4.9 to 5.1 mmol/L; abacavir: from 5.3 to 5.9 mmol/L). In multivariable analyses, both the treatment group (P = .002) and receipt of stavudine at baseline (P = .02) were independently associated with the change in total cholesterol, although there was no evidence of an interaction between the two (P = .98).
Using NCEP cut-offs, the proportion of patients with total cholesterol greater than 240 mg/dL (6.2 mmol/L) fell in tenofovir recipients from 38% at randomization to 25% at week 48 (P = .07, McNemar's Test), and rose in abacavir recipients from 28% to 36% (P = .39).40 No significant changes were seen in the proportion of patients with a raised LDL cholesterol level or a lowered HDL cholesterol level in either group. These data suggest that a within-class NRTI switch to tenofovir may also be modestly beneficial in selected patients with dyslipidemia.
As HIV infection becomes a chronic, manageable disease and members of the HIV-infected population age, we are likely to see an emergence of many chronically prevalent diseases, including diabetes mellitus and CVD. CVD risk data from the largest and longest studied cohorts in the setting of HIV infection suggest that cumulative years of exposure to combination ART increases the risk of myocardial infarction and stroke. Clinicians need to implement preventative and pre-emptive measures within the HIV population to slow the emergence of a potential CVD epidemic. As such, health care professionals need to consider CVD risk assessment as a routine component of the medical care of individuals with HIV infection.
There are several tactics appropriate to managing this long-term risk. The first includes the routine institution and consistent encouragement of therapeutic lifestyle changes, including smoking cessation, weight reduction, regular exercise and adherence to a Mediterranean diet rich in fresh fruits and vegetables and omega-3 fatty acids.
Another tactic involves considering the impact of specific antiretroviral agents on lipid levels and insulin resistance, which may be most appropriate at the time of treatment initiation. Comparative data are now helping to define the effects of different antiretroviral agents on lipid levels and insulin sensitivity, both of which may contribute to the establishment of the metabolic syndrome and contribute to future CVD risk. Differences have emerged between the NRTI, NNRTI and PI classes and between different combinations of these agents within treatment regimens. Thus, the effects of these drugs on lipids may be regimen specific rather than drug specific alone. Some newer agents such as atazanavir and tenofovir appear to have best-in-class lipid profiles, and the use of NNRTIs generally causes little change in the ratio of total cholesterol to HDL cholesterol. For individuals who are successfully established on a treatment regimen and who do not have resistance to specific agents, treatment switching should be considered as the preferred initial management approach for dyslipidemia and glucose intolerance. Clinical trials data suggest that within-class switching of PIs and NRTIs can improve a number of lipid parameters while achieving specific NCEP targets without the need for further interventions and/or a compromise of immunologic and virologic control of HIV.
Intervention with conventional lipid-lowering therapy, in accord with the guidelines set out by the NCEP ATP III, is recommended for individuals who do not achieve appropriate NCEP targets through treatment switching or for whom this option is not appropriate. The addition of lipid-lowering agents, including statins, ezetimibe and fibrates, to ART leads to changes in lipids similar, though to a lesser degree, than those observed in the general population; however, the changes in HIV-infected individuals are typically not sufficient to achieve NCEP targets.
Future research in the management of CVD risk includes the need to expand our understanding of the effects of individual antiretrovirals, including agents from new drug classes, on lipids and insulin resistance among both healthy volunteers and persons with HIV infection. Further details of drug interactions between lipid-lowering agents and antiretrovirals are also needed. More specifically, the effect of newer lipid-lowering agents, such as ezetimibe and rosuvastatin (Crestor), on the pharmacokinetics of antiretrovirals requires further investigation before these drugs can be widely recommended. Ongoing studies are more thoroughly evaluating specific switches, such as from zidovudine to tenofovir and from boosted PIs to boosted atazanavir. Details of the effects of these types of switches on glucose handling have not yet been reported but will be anxiously awaited to improve patient treatment options and care.
Copyright © 2006 Body Health Resources Corporation. All rights reserved.
This article was provided by TheBodyPRO.