Risk-benefit of HMG-CoA reductase inhibitors in the treatment of HIV protease inhibitor-related hyperlipidaemia

Penzak, Scott R.; Chuck, Susan K.

doi:10.1517/14740338.1.1.5

Cited by 25 publications

(5 citation statements)

References 50 publications

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“…Most of the available statins except pravastatin and fluvastatin, are metabolised through cytochrome isoenzyme CYP3A4, just as the PIs and NNRTIs are, providing concern for potential drug–drug interactions. Furthermore, statin therapy in patients using a PI-based regimen is in general not able to reduce the lipid concentrations to normal levels [49,50]. Studies on the effectiveness of gemfibrozil in patients on a PI-based regimen show conflicting results [51,52,53].…”

Section: Resultsmentioning

confidence: 99%

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: Resultsmentioning

confidence: 99%

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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“…We do not believe our findings can be explained by PLWH being severely ill or near death, which could prompt providers to discontinue ART, because we controlled for hospice use and our findings showed that the distribution of non-ART use was similar by end-of-life status during the follow-up. It is possible that some patients had pharmacological contraindications for ART use, for example, those who received statin treatment, 25 but we think that this is an unlikely explanation for our finding. Mental health conditions (e.g., anxiety and schizophrenia), which were relatively common in our sample, have been associated with poor adherence to ART, 26,27 but it is unclear how this would happen in an NH setting where medications are administered by patients by nursing staff.…”

Section: Discussionmentioning

confidence: 78%

Use of antiretroviral therapy in nursing home residents with HIV

Zhang

Shireman

Meyers

et al. 2022

J American Geriatrics Society

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Background Antiretroviral therapies (ARTs) are essential HIV care. As people living with HIV age and their presence in nursing homes (NHs) increases, it is critical to evaluate the quality of HIV care. We determine the rate of ART use and examine individual‐ and facility‐level characteristics associated with no ART use in a nationally representative long‐stay NH residents with HIV. Methods This retrospective cohort study included all long‐stay Medicare fee‐for‐service NH residents (2013–2016) with HIV who had a valid Minimum Data Set assessment. Residents were followed from long‐stay qualification until death, Part D disenrollment, transfer from long‐term care to another healthcare setting, or December 31, 2016. We identified individual and facility characteristics that were associated with non‐use of ART using generalized estimating equation logistic regression. Results Exactly 4171 eligible HIV+ residents from 2459 NHs were included in our study. Only 36% (1507 of 4171) received any ART regimen during an average of 11.6 months of observation. Older age, females, white race, receipt of Medicare skilled nursing benefits, and some major cardiometabolic comorbidities and mental health conditions were associated with non‐ART use. Rates of non‐ART use did not vary significantly by residents' end‐of‐life status (p = 0.21). Residents in facilities with a higher HIV concentration [adjusted odds ratio (adjOR) 3.42; 95% confidence interval (CI) 2.13–5.48] and an AIDS unit (adjOR 2.51; 95% CI 1.92–3.30) had higher odds of using an ART. Conclusions and Implications The rate of ART use by HIV+ long‐stay NH residents was low. Facilities' experience with HIV played an important role in ART receipt. Interventions to improve rates of ART use in NHs are urgently needed to ensure optimal health outcomes.

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“…CYP3A4 also metabolizes both simvastatin and lovastatin. When PIs act as inhibitor of CYP3A4, the levels of simvastatin and lovastatin may increase drastically 69 70 . This in turn increases the risk of toxicity of liver and skeletal muscle 71 .…”

Section: Pharmacogenomicsmentioning

confidence: 99%

Individualization of antiretroviral therapy - Pharmacogenomic aspect

Dalal¹,

Shankarkumar²,

Ghosh³

2015

Indian J Med Res

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Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy).

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Risk-benefit of HMG-CoA reductase inhibitors in the treatment of HIV protease inhibitor-related hyperlipidaemia

Cited by 25 publications

References 50 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

Use of antiretroviral therapy in nursing home residents with HIV

Individualization of antiretroviral therapy - Pharmacogenomic aspect

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