Lipid Changes in Patients Initiating Efavirenz- and Indinavir-Based Antiretroviral Regimens

Tashima, Karen T.; Bausserman, Linda; Alt, Elizabeth; Aznar, E. Ubiña; Flanigan, Timothy P.

doi:10.1310/f2v7-3r46-vx6j-241r

Cited by 49 publications

(6 citation statements)

References 16 publications

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“…But also patients with a normal HDL-c level, who are not at an increased CHD risk, showed marked increases in HDL-c. This baseline effect can likewise be distilled from the other studies, where those with the lowest baseline value (0.93 mmol/l; Atlantic study [12]) showed the largest HCL-c increase, while the smallest increase was seen in the study with the highest baseline value (1.23 mmol/l; Tashima study [13]). The study by Negredo et al [21], which included patients with similar baseline HDL-c levels as in the present study, showed an increase of HDL-c comparable to that in the present study (0.34 and 0.36 mmol/l, respectively).…”

Section: Discussionmentioning

confidence: 88%

“…Van der Valk et al reported an increase of HDL-c of 0.44 mmol/l for patients initiating treatment with didanosine, d4T, and NVP in the Atlantic trial [12]. Tashima et al reported an increase of HDL-c of 0.21 mmol/l in patients treated with EFV and either zidovudine plus 3TC, or indinavir [13], while Negredo et al showed an increased HDL-c concentration in therapy-naive patients starting a regimen of didanosine, d4T, and EFV (0.34 mmol/l) [22]. …”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, however, the changes in lipids and lipoproteins differ between patients using an ART regimen containing either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Whereas many of the PI-based regimens are often associated with increased levels of triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) [8,9,11], NNRTI-based regimens importantly differ from PI-based regimens by being associated with marked increases of HDL-c and lesser increases of LDL-c and TGs [12,13]. Notably, the increases in HDL-c demonstrated with NNRTI-containing ART markedly exceed those that may be induced with any of the currently licensed statins or fibrates [14].…”

Section: Introductionmentioning

confidence: 99%

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Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1

et al. 2004

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BackgroundPatients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV).Methods and FindingsProspective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417), or EFV (n = 289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p = 0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (−4.1%) and an increase for patients receiving EFV (+5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p = 0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs.ConclusionNVP-containing ART shows larger increases in HDL-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1

et al. 2004

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“…Previous studies have implicated efavirenz in worsening of lipid parameters (96). When combination drugs are created, adverse effects on metabolic indices could be amplified or attenuated due to the combined individual effects of each individual drug component.…”

Section: Multi-class Drug Combinationsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

Srinivasa

Grinspoon

2014

European Journal of Endocrinology

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In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks.

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“…Many antiretroviral regimens, including EFV, are related to adverse effects in serum lipids. This often necessitates lipid-lowering treatment ( 28 , 29 ). Multiple studies have shown that EFV demonstrate more negative changes in TC, TG, and LDL-C than elvitegravir (EVG) ( 30 – 32 ), raltegravir (RAL) ( 33 , 34 ), dolutegravir (DTG) ( 35 ), nevirapine (NVP) ( 36 ), and rilpivirine (RPV) ( 37 ) when used in people with HIV-1.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and effect on lipid profiles of switching to ainuovirine-based regimen versus continuing efavirenz-based regimen in people with HIV-1: 24-week results from a real-world, retrospective, multi-center cohort study

Wang,

Yu,

et al. 2024

Antimicrob Agents Chemother

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Ainuovirine (ANV), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), was approved in China in 2021. In a previous randomized phase 3 trial, ANV demonstrated non-inferior efficacy relative to efavirenz (EFV) and was associated with lower rates of dyslipidemia. In this study, we aimed to explore lipid changes in treatment-experienced people with human immunodeficiency virus (HIV)-1 (PWH) switching to ANV from EFV in real world. At week 24, 96.65% of patients in the ANV group and 93.25% in the EFV group had HIV-1 RNA levels below the limit of quantification (LOQ). Median changes from baseline in CD4 +T cell counts (37.0 vs 36.0 cells/µL, P = 0.886) and CD4+/CD8 +ratio (0.03 vs 0.10, P = 0.360) were similar between the two groups. The ANV group was superior to the EFV group in mean changes in total cholesterol (TC, −0.06 vs 0.26 mmol/L, P = 0.006), triglyceride (TG, −0.6 vs 0.14 mmol/L, P < 0.001), high-density lipoprotein cholesterol (HDL-C, 0.09 vs 0.08 mmol/L, P = 0.006), and low-density lipoprotein cholesterol (LDL-C, −0.18 vs 0.29 mmol/L, P < 0.001) at week 24. We also observed that a higher proportion of patients demonstrated improved TC (13.55% vs 4.45%, P = 0.015) or LDL-C (12.93% vs 6.89%, P = 0.017), and a lower proportion of patients showed worsened LDL-C (5.57% vs 13.52%, P = 0.017) with ANV than with EFV at week 24. In conclusion, we observed good efficacy and favorable changes in lipids in switching to ANV from EFV in treatment-experienced PWH in real world, indicating a promising switching option for PWH who may be more prone to metabolic or cardiovascular diseases.

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Lipid Changes in Patients Initiating Efavirenz- and Indinavir-Based Antiretroviral Regimens

Abstract: EFV and IDV independently elevate lipid levels. Alterations in the lipid levels may lead to increased cardiovascular risk in men, possibly mitigated by elevations in HDL cholesterol. In addition, changes in HDL cholesterol were significantly different between men and women.

Cited by 49 publications

References 16 publications

Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1

Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

Efficacy and effect on lipid profiles of switching to ainuovirine-based regimen versus continuing efavirenz-based regimen in people with HIV-1: 24-week results from a real-world, retrospective, multi-center cohort study

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