Evaluation of the Virological and Metabolic Effects of Switching Protease Inhibitor Combination Antiretroviral Therapy to Nevirapine-Based Therapy for the Treatment of HIV Infection

Abstract

Bordenave, B. Regions Hospital; Klebert, Michael; and Powderly, William G., ,"Evaluation of the virological and metabolic effects of switching protease inhibitor combination antiretroviral therapy to nevirapine-based therapy for the treatment of HIV infection." AIDS Research and Human Retroviruses.20,6. 589-594. (2004 ABSTRACTIn spite of indisputable benefits, the use of antiretroviral therapy is associated with multiple metabolic complications. Switching to simpler regimens might maintain viral suppression, improve metabolic side effects, and provide insight into the pathogenesis of these complications. Our objective was to carefully characterize the virological and metabolic effects of switching from a successful protease inhibitor (PI)-based antiretroviral regimen to a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with nevirapine (NVP).Forty patients, taking their first successful (less than 40 HIV RNA copies/ml) PI-based regimen, switched their PI to NVP. If patients did not tolerate NVP, substitution with efavirenz was allowed. The duration of the study was 48 weeks. At 12 weeks intervals subjects had multiple virological and metabolic parameters including glucose, insulin, C-peptide, glucagon, proinsulin, blood lipids, and lipoproteins. A subgroup of 18 patients also had body composition evaluations with DEXA scans and MRIs of the abdomen and the thighs as well as insulin tolerance tests. Ninety-five percent of the patients maintained viral suppression (95% CI 88-100%); only one patient failed and another developed hepatitis. There were improvements in glucose (decreased fasting glucose, insulin, and improved insulin tolerance) and lipid metabolism (decreased triglycerides and increased HDL), but no changes in body composition and bone mineral density. Our study supports a pathogenic role for PIs in the development of hypertriglyceridemia and insulin resistance, but a more limited role in the fat redistribution syndrome. 589

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs

“…Efavirenz, nevirapine, raltegravir, tenofovir, abacavir, and lamivudine have been associated with lower risk of mitochondrial toxicity, and low DM risk (44,45,46). In addition, newer PI, especially atazanavir and darunavir, have been shown to have lower metabolic toxicity and to rarely cause IR (47,48,49,50,51), a fact that could even explain the improvement of IR in pretreated patients switching to these drugs, as previously described with atazanavir, efavirenz, or nevirapine (47,52). However, the cross-sectional inclusion of our patients precludes us to know whether lower IR found in pretreated patients is due to persistence of this complication or is the result of progressive decrease with the use of new drugs with a lower toxicity.…”

Real-Time Nucleic Acid Sequence–Based Amplification Assay to Quantify Changes in Mitochondrial DNA Concentrations in Cell Cultures and Blood Cells from HIV-Infected Patients Receiving Antiviral Therapy

“…Samples were selected from 19 patients who were part of a clinical trial in which patients with undetectable viral load on a stable protease inhibitor regimen continued that regimen for 6 months or switched the protease inhibitor to nevirapine. Details of these studies have been published elsewhere (19 ). This group allowed us to evaluate the changes over time of mtDNA in a variety of antiretroviral regimens and the effects of substituting the protease inhibitor for nevirapine, maintaining the nucleoside analog part of the regimen.…”

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy

“…Some studies demonstrated accelerated bone loss, while others showed stable or even increased BMD over time. [7][8][9] A meta-analysis reported that in studies that involved treatment-naive or untreated persons at baseline, BMD significantly declined at 1, 2, and 2.5 years after cART initiation. Conversely, in cohorts that involved cART-treated persons at baseline, BMD was stable over time.…”