Screening for and managing dyslipidemia in people with HIV.
* First patient visit
* When starting or changing antiretroviral therapy (ART)
* Every 6 months if the last measures had an abnormal result
* Every 12 months if the last measures were normal
Other HIV guidelines suggest some wrinkles to this plan. IDSA/HIVMA experts advise retesting lipids 1 to 3 months after starting ART. (2) HRSA HIV guidelines suggest monitoring as often as every 4 to 6 weeks in people with dyslipidemia, until the low-density lipoprotein cholesterol (LDL-C) goal is met, then every 4 to 6 months. (3) However, dyslipidemia in many people with HIV entails high triglycerides and low high-density lipoprotein cholesterol (HDL-C) rather than high LDL-C. And a portion of HIV-positive people who do have high LDL-C never reach their target with therapy.
Managing dyslipidemia with HIV: where to start
When planning how to treat dyslipidemia in people with HIV, DHHS guidelines (1) recommend consulting current National Lipid Association (NLA) advice. (4) That's a logical place to start--and a logical place to continue, now that part 2 of the NLA tract offers a special section on people with HIV. (5)
NLA guidance on starting antilipid drug therapy in the general population combines two variables: (1) level of LDL-C or non-HDL-C, and (2) an atherosclerotic cardiovascular disease (ASCVD) risk score. (4) (See Table 1 footnote for ASCVD risk factors.) Based on this detailed advice, HRSA HIV guidelines offer a simplified scheme suggesting when to start lifestyle interventions and when to consider drug therapy (Table 1). (3) In people with high triglycerides--a frequent lipid problem in people with HIV--HRSA recommends drug therapy to get triglycerides below 500 mg/dL to prevent pancreatitis, then focusing on LDL-C (Table 2).
So much has been written--and continues to be written--about managing dyslipidemia in people with HIV that one could easily fill several issues of RITA dissecting it. Rather than attempting such a feat, this review will offer selected insights into lifestyle changes and treatment with statins and other medications, while pointing readers to current worthy reviews (see "Some worthy HIV lipid management reviews").
Changing lifestyles to change lives
More than a few clinicians cringe at entreaties to start lipid management with lifestyle modifications. It's so much easier to start a statin--but also much riskier to put a patient on a potentially lifelong therapy that carries its own risks and interacts with antiretrovirals and many other drugs. Getting people to exercise, adopt a healthy diet, and quit smoking can be tough, but statistics show it can be done.
* Quitting smoking has a huge HIV cardio impact.
Smoking lowers HDL-C6 and heightens the cardio vascular risk conferred by dyslipidemia. Analysis of 29,515 HIV-positive North Americans determined that if these people never smoked, they would avert 38% of lifetime myocardial infarctions. (7) (See page 26 of this issue for details.)
* Many smokers quit for good.
In the United States smokers make up 42% of the HIV population but only 21% of the general population. (8) Yet this 419,945-person analysis counted lots of quitters in the HIV contingent: 1 in 5 had stopped smoking. And the general US population now has more former smokers than current smokers. (9)
Impact of dietary factors on cardiometabolic death
* Effective online quitting tool for HIV smokers.
An 8-session online interactive program designed for people with HIV, Positively Smoke Free, (10) is already helping HIV-positive people quit. (11)
* Quick-and-easy dietary do-list.
For clinicians who work with a good dietician, referring HIV-positive people with bad diets or poor weight control makes lots of sense. But for providers without a savvy diet planner at their elbow, quick-and-easy eating pointers could help. And a bounty of such tips just arrived from a big analysis by the US National Health and Nutrition Examination Surveys (NHANES) (Figure 1). (12) A comparative risk assessment model incorporating data on population demographics and dietary habits figured that the biggest fractions of diet-related cardiometabolic deaths could be traced to too much sodium, too few nuts/ seeds, too many processed meats, not enough seafood omega-3 fats, too few vegetables, too few fruits, and too many sugar-sweetened drinks.
* Saturated fat intake is triglyceride culprit in HIV group.
A comparison of 356 people with HIV and metabolic problems (55% men, 44% nonwhite) and 162 HIVnegative community-dwelling individuals found significantly greater intake of total fat, saturated fat, cholesterol, and calories from saturated fat and trans fat in the HIV group. (13) Saturated fat intake correlated positively with triglycerides, which were 8.7 mg/dL higher with every additional gram of saturated fat. Total fat intake was inversely associated with triglyceride level.
* Quarterly dietary follow-up prevents dyslipidemia with ART.
A National Cholesterol Education Program diet with follow-up every 3 months maintained total cholesterol and LDL-C while lowering triglycerides in a small open-label randomized trial of people starting ART in Brazil. (14) After 1 year of follow-up, 21% of people in the diet group compared with 68% in the control group, which got general dietary counseling without follow-up, (15) had a lipid profile indicating dyslipidemia (P < 0.001). Fat intake fell in the diet group but not in the control group.
* How much exercise has a lipid impact?
The National Lipid Association recommends 150 minutes of moderate to higher intensity aerobic activity weekly to lower triglycerides and sometimes raise HDL-C. (5) Boosting that level to 200 to 300 minutes per week can improve triglycerides, HDL-C, and LDL-C while trimming body fat and weight.
Key statin advice and findings in people with HIV
Research confirms lowered atherosclerotic cardiovascular event risk with statins, (5) which remain the first drug choice to control dyslipidemia in people with HIV. (5) As in the general population, the US National Lipid Association (NLA) recommends starting with lifestyle changes in people with HIV, then proceeding to statin therapy. (5) People with triglycerides over 500 mg/dL are an exception; they may need to start a fibrate to control the high triglycerides before addressing other lipid abnormalities (Table 3). The NLA and others offer the following advice on antilipid therapy in general--and statin therapy in particular--for people with HIV:
* Setting lipid goals for people with HIV.
"HIV-infected patients should be treated similarly to the general population," the National Lipid Association says, "with atherogenic cholesterol goals according to the NLA Part 1 Recommendations (4) with the caveat of considering the presence of HIV infection an additional major ASCVD risk factor." (5) Whether treatment goals should be more aggressive in people with HIV, as in people with other high-risk features (Table 1), remains unknown. (5)
* Which HIV patients should start statins?
According to the European AIDS Clinical Society (EACS), "statins should be used by all those with established vascular disease and among those with type 2 diabetes or at high risk of cardiovascular disease, irrespective of lipid levels." (16) HRSA HIV guidelines offer cutoffs for starting antilipid drug therapy in general (Tables 1 and 2) and advice on using statins or other antilipid agents for specific lipid abnormalities (Table 3). (3)
* Which statin to try.
The National Lipid Association recommends atorvastatin, rosuvastatin, or pitavastatin as "generally preferred agents" for people with HIV. (5) Pitavastatin is the only statin that does not interact with antiretrovirals and requires no dose adjustments, whereas atorvastatin and rosuvastatin may require dose adjustments. (5) But the ACC/AHA considers higher doses of atorvastatin and rosuvastatin as "high-intensity statins," (17) and HIV cardiologist Christopher Longenecker underlines the need for high-intensity statins in people with HIV (see Table 1 on page 21). Despite pitavastatin's clean interaction profile, the ACC/AHA ranks it as a low-intensity statin.
Pravastatin has limited interactions with antiretrovirals but trails atorvastatin and rosuvastatin in potency. (5) Lovastatin and simvastatin are contraindicated with all protease inhibitors and with cobicistat. (5) Statins do not have significant interactions with nucleosides or integrase inhibitors (except when boosted by cobicistat). (5)
In studies involving people with HIV, rosuvastatin lowered LDL-C and triglycerides more than atorvastatin or pravastatin in two small randomized trials, (18,19) while in a 700-person retrospective analysis, rosuvastatin and atorvastatin lowered total cholesterol, LDL-C and non-HDL-C more than pravastatin. (20) After 52 weeks in a 252-person double-blind US trial, pitavastatin lowered LDL-C (but not triglycerides) significantly more than pravastatin, with similar rates of treatment-emergent adverse events. (21) Though 96 weeks in a double-blind placebo-controlled trial enrolling 147 antiretroviral-treated people with HIV, rosuvastatin significantly slowed intima-media thickness progression. (22) Through 12 months in a double-blind placebo-controlled trial involving 37 HIV-positive people with subclinical coronary atherosclerosis and LDL-C below 130 mg/dL, atorvastatin significantly reduced noncalcified coronary plaque volume and number of high-risk plaques. (23)
A 2015 systematic review of 18 clinical trials of statins in people with HIV concluded that (1) atorvastatin, pravastatin, and rosuvastatin are safe, well-tolerated, and efficacious in lowering LDL-C, (2) atorvastatin and rosuvastatin are more potent than pravastatin and "decrease the burden of subclinical cardiovascular disease," and (3) pitavastatin has "a particularly favorable pharmacokinetic profile" even with protease inhibitors. (24) In people with HIV, a large US trial summarized above (21) and a small Thai trial (25) recorded significant reductions in LDL-C with pitavastatin.
* Start a statin, a fibrate, or something else?
HRSA guidelines offer clear direction on which type of antilipid drug to start for which type of lipid abnormality (Table 3). (3)
* How can statin drug interactions be tracked?
In 2012 the FDA summarized statin-antiretroviral interactions and outlined statin dose limitations. (26) The National Lipid Associations offers a statin-by-statin guide to interactions with protease inhibitors, cobicistat, and nonnucleosides in Table 23 at the link provided at reference 5 below. DHHS antiretroviral guidelines provide detailed tables on interactions and dose adjustments with statins and protease inhibitors (Table 19a), nonnucleosides (Table 19b), and integrase inhibitors (Table 19d) at the link provided at reference 1 below. The University of Liverpool HIV Drug Interaction Checker (http://www.hiv-druginteractions.org/) is a regularly updated tool that allows users to check interactions between individual antiretrovirals and other major drugs, including statins.
* Statins remain underprescribed in people with HIV.
Several studies have reached this conclusion, (27-30) most recently an 86,535-person analysis of 13 US and 2 Canadian HIV cohorts, (30) which found that more than half of these people were eligible for statins but not getting them. National Lipid Association experts suggest the big gap between eligibility and prescription reflects relatively low prevalence of high LDL-C in HIV populations, potential statin side effects, and drug-drug interactions. (5) The National Lipid Association and this review cite numerous studies showing statins are safe and effective in people with HIV and have the added potential benefit of reducing chronic inflammation.
* Smoking and diabetes tied to LDL-C target failure with statins.
A study of 434 HIV-positive or negative men in the Multicenter AIDS Cohort Study (MACS) found that 31 of 230 with HIV and 29 of 204 without HIV and receiving statin therapy had not achieved the LDL-C target at a MACS visit between October 2011 and March 2012 (13.5% versus 14.2%, P = 0.82). (31) Factors independently associated with not hitting the LDL-C target were current smoking (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.30 to 5.67) and diabetes (OR 5.31, 95% CI 2.47 to 11.42). A 958-person Swiss HIV Cohort Study analysis confirmed the link between diabetes and failure to reach a total cholesterol target. (32) Other factors predicting treatment-resistant total cholesterol in the Swiss study were older age, history of coronary heart disease, higher initial total cholesterol, and longer time time taking a protease inhibitor and/or a nonnucleoside.
* Do statins help HIV-positive people not eligible by lipid criteria?
Two placebo-controlled trials in HIV-positive people with low LDL-C found that rosuvastatin or atorvastatin slowed intima-media thickness progression or reduced noncalcified coronary plaque volume. (22,23) But the National Lipid Associations maintains "it is not clear whether statins should be used more aggressively in persons with HIV infection" to prevent cardiovascular disease.5 A large randomized trial to address that question, REPRIEVE, began in 2015 and has a target completion date of April 2020. (33) REPRIEVE is still recruiting HIV-positive 40- to 75-year-olds on ART but not eligible for statins by lipid criteria and randomizing them to once-daily pitavastatin or placebo.
* More statin use with HIV/HCV means less cirrhosis.
A study of 5985 HIV/HCV-coinfected US veterans used Cox proportional hazards analysis to determine that in people with alanine aminotransferase at 40 IU/L or lower, every 30% longer time on statins cut risk of incident cirrhosis 32% (hazard ratio 0.68, 95% CI 0.47 to 0.98). (34)
* What about the higher risk of diabetes with statins?
For the general population, the FDA concluded that the cardiovascular benefits of statins outweigh any diabetes risk. (35) In the INTREPID trial pitavastatin had no significant impact on glucose homeostasis in people with HIV. (21) Experts recommend assessing HIV patients for diabetes risk before starting a statin and monitoring them during statin use for changes in blood glucose and HbA1c. (36)
* Where do niacin, fibrates, ezetimibe, and fish oils fit in?
A 2014 meta-analysis of statin trials in the general population found wide interindividual variations in LDL-C and non-HDL-C responses. (37) The National Lipid Association says findings like these demonstrate "that statin therapy alone may be insufficient for some individuals to reach goal and [support] the recommendation to consider combination drug therapy." (4) Also, statins may be inappropriate for people with isolated high triglycerides (Table 3).
The HRSA HIV care guide offers advice on whether to start with a statin, a fibrate, niacin, or omega-3 fatty acids (fish oils) for specific lipid abnormalities (Table 3). (3) All of these agents, plus ezetimibe (which inhibits intestinal absorption of cholesterol), have also been studied in people with HIV. Tables 4-6 summarize selected trials of these agents in HIV populations. HRSA guidelines make these general points:
* "Fibrates may be considered as an alternative or adjunct to statins ... When given concomitantly, statins and fibrates increase the risk of rhabdomyolysis and must be used cautiously and with careful monitoring." (3)
* "Niacin may be effective as adjunctive therapy, but it has not been shown to decrease CHD events. It may worsen insulin resistance and may cause hepatotoxicity. It also causes uncomfortable flushing in some patients; the sustained-release formulations are better tolerated." (3)
* "Ezetimibe (Zetia) appears to be effective in combination with statins for patients whose cholesterol is not controlled adequately with a statin alone, but it also has not been shown to decrease CHD events." (3)
* "Bile acid sequestrants generally should be avoided because they may interfere with the absorption of other drugs and may increase triglyceride levels." (3)
* How well do niacin, fibrates, ezetimibe, and fish oils work in people with HIV?
In single-arm and randomized trials over the past decade (Tables 4-6), these agents always improved certain measures of abnormal lipids in people with HIV but often met standard lipid treatment goals only in small proportions of participants. Combined fibrate/statin (40) or fibrate/niacin (41) therapy worked better than single-agent therapy in two trials. Ezetimibe successfully lowered LDL-C or non-HDL-C, (42-44) and fish oils (omega-3 fatty acids) cut high triglycerides; (45-50) neither ezetimibe nor fish oils interact with antiretrovirals. Throughout these studies, (38-50) antilipid agents were usually safe but often failed to meet secondary goals, such as improving flow-mediated dilation. (39,50) The drugs had mixed impacts on markers of inflammation. (39,42,46,48,50)
* Meta-analyses find fish oils cuts TG 80 to 100 mg/dL with HIV.
Two meta-analyses of fish oil (omega-3 fatty acid) trials in people with HIV found similar short-term impacts on triglycerides. An analysis of four studies of 900 to 3360 mg of fish oils daily for 8 to 16 weeks yielded a weighted mean triglyceride reduction of 80.34 mg/dL. (51) Metaanalysis of seven randomized trials of fish oils for 12 to 24 weeks figured an average triglyceride drop of 99.2 mg/ dL with fish oils. (52)
* Meta-analysis suggests fish oils lower heart disease risk.
A general-population meta-analysis of 18 randomized controlled trials found a nonsignificant reduction in coronary heart disease risk with fish oils from food or supplements (summary relative risk estimate [SRRE] 0.94, 95% CI 0.85 to 1.05). (53) The coronary heart disease risk reduction with fish oils became significant in people with high triglycerides (SRRE 0.84, 95% CI 0.72 to 0.98) or high LDL-C (SRRE 0.86, 95% CI 0.76 to 0.98). Meta-analysis of 16 prospective cohort studies found almost a 20% lower risk of coronary heart disease with fish oils (SRRE 0.82, 95% CI 0.74 to 0.92). To improve cardiovascular health, the American Heart Association calls for at least two 3.5-oz servings of fish weekly--preferably oily fish. (54)
* Will PCSK9 inhibitors have a role in HIV dyslipidemia?
The PCSK9 inhibitors alirocumab (Praluent) and evolocumab (Repatha) increase LDL-receptor expression on hepatocytes and thus promote elimination of LDL-C reflected by lower levels in blood. (55) Statins exploit the same mechanism by inhibiting HMG-CoA reductase. Fully humanized monoclonal antibodies delivered by injection every 2 or 4 weeks, PCSK9 inhibitors are licensed as an adjunct to diet and maximally tolerated statins in people with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. At a hefty cost exceeding $14,000 yearly (wholesale), PCSK9 inhibitors are not cost-effective by standard criteria. (56)
As Christopher Longenecker points out in the interview starting on page 16, research shows that HIV-positive people have higher levels of PCSK9 in blood (57) and thus could be candidates for PCSK9 inhibitors when other treatments fail. Longenecker observes that the safety of PCSK9 inhibitors in people with HIV remains to be determined, as does their clinical impact in people with or without HIV.
* What to do when no treatment strategy achieves lipid targets.
In its advice on dyslipidemia in people with HIV, the National Lipid Association reminds clinicians that "atherogenic cholesterol goals may not be attainable in all patients, but there is incremental benefit to lowering non-HDL-C and LDL-C to approach these goal levels." (5) For example, one general-population analysis figured that every 38.7 mg/dL reduction in LDL-C with statin therapy lowered chances of major cardiovascular events 22% after about 5 years of statin therapy, compared with placebo or less intensive statin therapy. (58)
Some worthy HIV lipid management reviews
* General population
Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol. 2015; 9:129-169. http://www.lipidjournal.com/article/S1933-2874(15)00059-8/pdf
Jacobson TA, Maki KC, Orringer CE, et al. National Lipid Association recommendations for patientcentered management of dyslipidemia: part 2. J Clin Lipidol. 2015; 9(6 Suppl):S1-122. http://www.lipidjournal.com/article/S1933-2874(15)00380-3/pdf Includes section on HIV infection.
Myerson M, Malvestutto C, Aberg JA. Management of lipid disorders in patients living with HIV. J Clin Pharmacol. 2015; 55:957-974. http://onlinelibrary.wiley.com/doi/10.1002/jcph.473/epdf
Eckard AR, McComsey GA. The role of statins in the setting of HIV infection. Curr HIV/AIDS Rep. 2015; 12:305-312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860807/pdf/nihms780235.pdf
da Cunha J, Maselli LM, Stern AC, Spada C, Bydlowski SP. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs. World J Virol. 2015; 4:56-77. http://www.wjgnet.com/2220-3249/full/v4/i2/56.htm
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Table 1. HRSA guidelines on managing high LDL-C with HIV (3) Risk category LDL-C goal Lower risk: No CHD or CHD <160 mg/dL (<4.1 mmol/L) risk equivalents * and 0-1 risk factors ([dagger]) Moderate risk: No CHD or <130 mg/dL (<3.4 mmol/L) CHD risk equivalents and [greater than or equal to] 2 risk factors and 10-y estimated risk <10% Moderately high risk: No <130 mg/dL (<3.4 mmol/L) CHD or CHD risk Optional goal <100 mg/dL equivalents and [greater than or equal to] 2 risk factors and 10-y estimated risk 10-20% High risk: CHD or CHD <100 mg/dL (<2.6 mmol/L) risk equivalent Optional goal <70 mg/ dL ([double dagger])) Risk category Start therapeutic lifestyle changes Lower risk: No CHD or CHD LDL-C [greater than or risk equivalents * and equal to] 160 mg/dL (>4.1 0-1 risk factors mmol/L) ([dagger]) Moderate risk: No CHD or LDL-C [greater than or CHD risk equivalents and equal to]130 mg/dL [greater than or equal ([greater than or equal to] 2 risk factors and to] 3.4 mmol/L) 10-y estimated risk <10% Moderately high risk: No LDL-C [greater than or CHD or CHD risk equal to] 130 mg/dL equivalents and [greater ([greater than or equal than or equal to] 2 risk to] 3.4 mmol/L) factors and 10-y estimated risk 10-20% High risk: CHD or CHD LDL-C [greater than or risk equivalent equal to] 100 mg/dL ([greater than or equal to] 2.6 mmol/L) Risk category Consider drug therapy Lower risk: No CHD or CHD LDL-C [greater than or risk equivalents * and equal to] 190 mg/dL 0-1 risk factors ([greater than or equal ([dagger]) to] 4.9 mmol/L); drug therapy optional at 160-189 mg/dL Moderate risk: No CHD or LDL-C [greater than or CHD risk equivalents and equal to] 160 mg/dL [greater than or equal ([greater than or equal to] 2 risk factors and to] 4.1 mmol/L) 10-y estimated risk <10% Moderately high risk: No LDL-C [greater than or CHD or CHD risk equal to] 130 mg/dL equivalents and [greater ([greater than or equal than or equal to] 2 risk to] 3.4 mmol/L) factors and 10-y estimated risk 10-20% High risk: CHD or CHD LDL-C [greater than or risk equivalent equal to] 100 mg/dL ([greater than or equal to] 2.6 mmol/L) CHD, coronary heart disease; LDL-C, low-density lipoprotein cholesterol. * Risk equivalents are diabetes, peripheral vascular disease, symptomatic carotid artery disease, abdominal aortic aneurysm, transient ischemic attack, and [greater than or equal to] 2 CHD risk factors with a 10-year CHD risk >20%. ([dagger]) Risk factors are male sex; age [greater than or equal to] 45 in men, [greater than or equal to]55 in women; current cigarette smoking; family history of CHD <55 years of age in male first-degree relative, <65 in female first-degree relative; blood pressure [greater than or equal to] 140/90 mm Hg or blood pressure medication; HDL-C <40 mg/dL in men, <50 mg/dL in women. ([double dagger]) Goal preferred by many cardiologists for people with CHD or CHD risk equivalents. Table 2. HRSA guidelines on managing high triglycerides with HIV (3) Risk category Triglyceride Begin therapy level Normal triglycerides <150 mg/dL Borderline high 150-199 mg/dL * triglycerides High triglycerides 200-499 mg/dL Start therapeutic lifestyle changes; consider drug therapy for people with CHD, CHD equivalents, ([dagger]) or high risk Very high triglycerides [greater than Start therapeutic or equal to] lifestyle changes; 500 mg/dL consider drug therapy CHD, coronary heart disease. * Some experts recommend lifestyle intervention in this range. See Myerson et al. in "Some worthy HIV lipid management reviews." ([dagger]) Risk equivalents are diabetes, peripheral vascular disease, symptomatic carotid artery disease, abdominal aortic aneurysm, transient ischemic attack, and [greater than or equal to] 2 CHD risk factors with a 10-year CHD risk >20%. Table 3. Which antilipid drug for which abnormality? Lipid abnormality First Second choice choice Isolated high LDL-C or non-HDL-C Statin Fibrate Isolated high TG * Fibrate Statin, omega-3 fatty acids High LDL-C and TG 200-500 mg/dL Statin Fibrate High LDL-C and TG >500 mg/dL * Fibrate Omega-3 fatty acids, niacin, statin HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides. Source: US Department of Health and Human Services. (3) * For triglycerides at or above 500 mg/dL that do not respond to lifestyle modification, the National Lipid Association recommends a fibrate (preferably fenofibrate) or prescription omega-3 fatty acids. (5) Table 4. Selected trials of niacin and/or fibrate for dyslipidemia in people with HIV Author, year Study design * n * Dube, (38) 2006 Nondiabetic men with TG 33 [greater than or equal to] 200 mg/dL and non-HDL-C [greater than or equal to] 180 mg/dL took escalating doses of extended-release niacin up to 2000 mg nightly for 44 wk (ACTG A5148) Dube, (39) 2015 Patients with low HDL-C (men 74 <40 mg/dL, women <50 mg/dL) and TG >150 mg/dL randomized open-label to extended-release niacin plus aspirin or to fenofibrate for 24 wk (ACTG A5293) Aberg, (40) 2005 Patients with LDL-C 174 [greater than or equal to] 130 mg-dL and TG [greater than or equal to] 200 mg- dL randomized open- label to daily fenofibrate or pravastatin; if composite lipid goal not reached in 12 wk, agents combined in wk 12-48 (ACTG 5087) Balasubramanyam, Patients with TG >150 mg/ dL 191 (41) 2011 randomized for 24 wk to (1) usual care, (2) diet plus exercise (D/E), (3) D/E + fenofibrate, (4) D/E + niacin, (5) D/E + F/N For fenofibrate and/or fish oil trial, see Gerber in Table 6 Author, year Main results Dube, (38) 2006 At week 48 median total cholesterol (-8.1 mg/dL), non-HDL-C (-18.9 mg/dL and TG (-153.2 mg/dL) declined; no persistent hyperglycemia Dube, (39) 2015 In men HDL-C rose 3 mg/dL with niacin and 6.5 mg/dL with fenofibrate (P < 0.001 for both); in women HDL-C rose 16 mg/dL with niacin and 8 mg/ dL with fenofibrate (P = 0.08 for both); brachial artery flow-mediated dilation did not change significantly in either arm Aberg, (40) 2005 Composite goal reached at 12 wk by 1% on fenofibrate (F), 5% on pravastatin (P) at week 48, 7% on F+P and 3% on P+F achieved goal; median LDL-C decrease at 48 wk -8 mg/dL with F+P, -14 mg/dL with P+F Balasubramanyam, D/E + F improved TG, total (41) 2011 cholesterol, non-HDL-C; D/E + N improved HDL-C D/E + F/N had maximum impact vs usual care: TG -52%, non-HDL-C -18.5%, HDL-C +12%, T-to-HDL-C ratic -24.5% * All participants adults on stable antiretroviral therapy. Table 5. Selected trials of ezetimibe for dyslipidemia in people with HIV Author, year Study design * n * Wohl, (42) 2008 Patients with LDL-C 48 [greater than or equal to] 75 mg/dL, TG [less than or equal to] 800 mg/dL randomized double-blind to crossover of daily ezetimibe vs placebo for 6 w with 2-w washout between Chow, (43) 2009 Patients with LDL-C >130 44 mg/dL with stable statin randomized double-blind to crossover of ezetimibe vs placebo for 12 w with 4-w washout between Saeedi, (44) 2015 Patients short of lipid 43 goal on 10-mg rosuvastatin randomized open-label to add ezetimibe or raise statin to 20 mg for 12 wk Author, year Main results Wohl, (42) 2008 LDL-C -5.3% with ezetimibe vs + 5.5% with placebo (P = 0.04) Chow, (43) 2009 Median difference in absolute LDL-C between ezetimibe and placebo -32 mg/dL (P < 0.0001) Saeedi, (44) 2015 With ezetimibe significantly greater declines in total cholesterol, non-HDL-C, and triglycerides * All participants adults on stable antiretroviral therapy. Table 6. Selected trials of fish oils for dyslipidemia in people with HIV Author, year Study design * n * Wohl, (45) 2005 Patients with TG >200 mg/ 52 dL randomized open-label to dietary + exercise counseling or to D/E counseling plus fish oils for 16 wk Gerber, (46) 2009 Patients with TG [greater 100 than or equal to] 400 mg/dL randomized open-label to fish oils or fenofibrate for 8 wk; if TG >200 mg/dL at week 8, fish oils and fenofibrate combined for wk 10-18 (ACTG A5186) Peters, (47) 2012 Patients with TG 300-1000 48 mg/ dL randomized double-blind to fish oils or placebo for 12 wk Metkus, (48) 2013 Patients with TG [greater 48 than or equal to] 200 mg/dL randomized double-blind to fish oils or placebo for 8 wk Paranandi, (49) 2014 Patients with TG [greater 41 than or equal to] 150 mg/dL randomized double-blind to crossover of fish oils vs placebo for 12 wk followed by 4-wk washout Volpe, (50) 2016 Patients with TG 150-2500 117 mg/ dL randomized to fish oils or placebo for 24 months Author, year Main results Wohl, (45) 2005 Fish oils group had mean 16-wk TG decline of 19.5% vs 5.7% with counseling alone (not significant at P = 0.12); LDL-C rose 22.4% at wk 16 with fish oils but did not change with counseling Gerber, (46) 2009 Median TG dropped 46% with fish oils alone, 58% with fenofibrate alone, 65.5% with combination; TG<200 mg/dL in 22.7% with combination Peters, (47) 2012 TG fell by median 154.9 mg/dL with fish oils but rose 36.3 mg/dL with placebo (P = 0.019) Metkus, (48) 2013 TG decreased by median 34 mg/dL with fish oils but rose 46.5 mg/dL with placebo (P = 0.01) Paranandi, (49) 2014 Mean TG decreased significantly with fish oils (-63.2 mg/dL, P < 0.001); total cholesterol, LDL-C, or HDL-C did not change Volpe, (50) 2016 Median TG decreased significantly more with fish oils than placebo (-68 vs -22 mg/dL, P = 0.041); no significant difference in HDL-C * All participants adults on stable antiretroviral therapy. Figure 1. Analysis of the National Health and Nutrition Examination Surveys (NHANES) determined that seven dietary factors accounted for similar proportions of all cardiometabolic deaths in the general US population. (12) Impact of dietary factors on cardiometabolic death Percent of all cardiomet deaths Excess sodium 9.5% Too few nuts/needs 8.5% Excess processed meats 8.2% Too little fish oil 7.8% Too few vegetables 7.6% Too few fruits 7.5% Excess sugary drinks 7.4% Note: Table made from bar graph.
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|Publication:||Research Initiative/Treatment Action!|
|Date:||Mar 22, 2017|
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