Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA

Clumeck, Nathan; Goebel, F. D.; Rozenbaum, Willy; Gerstoft, Jan; Staszewski, Schlomo; Montaner, Julio S. G.; Johnson, Margaret; Gazzard, Brian; Stone, Chris; Athisegaran, Rayma; Moore, Sarah

doi:10.1097/00002030-200108170-00009

Cited by 134 publications

(78 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, the TZV regimen was well tolerated over 96 weeks and the safety profile did not change over time. Thus, the incidence of adverse events in the TZV group at 96 weeks was comparable to that reported in other studies that have evaluated ABC/3TC/ZDV over 48 weeks [13,14]. The greater elevation of serum lactate in the d4T/3TC/NFV group is consistent with earlier studies showing d4T to be associated with most NRTI-related cases of hyperlactataemia, which may be related to the greater mitochondrial toxicity profile of this thymidine compared to other NRTIs [30].…”

Section: Discussionsupporting

confidence: 86%

A prospective, 96‐week study of the impact of Trizivir^®, Combivir^®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

et al. 2006

View full text Add to dashboard Cite

To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir s (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir s (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM) 1 nelfinavir (NFV), and stavudine (d4 T) 1 lamivudine (3TC) 1 NFV. Study designAn international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 nondiabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of 41000 HIV-1 RNA copies/mL and 200 000 copies/mL and a CD4 cell count of 450 cells/mL. MethodsPatients were randomized 1 : 1 : 1 to TZV twice daily (n 5 85), COM/NFV 1250 mg twice daily (n 5 88), or d4T 40 mg 1 3TC 150 mg 1 NFV 1250 mg twice daily (n 5 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA o50 and o400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions. ResultsThe study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline lowdensity lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log 10 copies/mL and CD4 cell count was 355 cells/mL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, À 8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV ( 1 29 and 1 19 mg/dL, respectively; Po0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV ( 1 1 vs 1 39 mg/dL; P 5 0.003). Total cholesterol4200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P 5 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms. 85 ConclusionsOver 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses.

show abstract

Section: Discussionsupporting

confidence: 86%

A prospective, 96‐week study of the impact of Trizivir^®, Combivir^®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

et al. 2006

View full text Add to dashboard Cite

show abstract

“…With regard to the major side effects associated with the use of PIs, alternative therapies have been proposed to replace the PIs with abacavir (42,43) or by the NNRTI nevirapine (44 -46) or efavirenz (47,48). These approaches appear successful to control HIV infection, particularly with the NNRTI (43).…”

mentioning

confidence: 99%

In Vitro Suppression of the Lipogenic Pathway by the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz in 3T3 and Human Preadipocytes or Adipocytes

Hadri

Glorian

Monsempes

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

A serious metabolic syndrome combining insulin-resistance, dyslipidemia, central adiposity, and peripheral lipoatrophy has arisen in HIV-infected patients receiving highly active antiretroviral therapy. The aim of this work was to examine the effects of the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz on adipocyte differentiation and metabolism. When induced to differentiate in the presence of efavirenz (5-50 M), 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol droplets. This phenomenon was rapidly reversible and was also readily detectable in the 3T3-L1 preadipose cell line and in primary cultures of human preadipocytes. When applied to mature 3T3-

show abstract

“…Although such a measurement is subjective, the low number of daily pills and the good tolerability of the simplified regimen are important features of a long-term therapeutic strategy and may help to maintain antiviral efficacy. This is confirmed by additional randomized studies examining the switch from PIs to either abacavir or nevirapine, which have reported easier adherence and improved quality of life for patients who switched [18,33].…”

Section: Discussionmentioning

confidence: 62%

A Randomized Trial of Simplified Maintenance Therapy With Abacavir, Lamivudine, and Zidovudine in Human Immunodeficiency Virus Infection

&NA;

2002

Infectious Diseases in Clinical Practice

View full text Add to dashboard Cite

This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens (n ¼ 79) or a change to the simplified regimen of abacavir-lamivudine-zidovudine (n ¼ 84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1) RNA for >6 months who did not have the reverse transcriptase 215 mutation. After a median follow-up of 84 weeks, virologic failure was 6% in the continuation and 15% in the simplified group (P ¼ .081). Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure. Study treatment was discontinued because of adverse events in 20% of the continuation and 7% of the simplified group (P ¼ .021). Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels; however, this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen.

show abstract

Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA

Abstract: The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.

Cited by 134 publications

References 18 publications

A prospective, 96‐week study of the impact of Trizivir^®, Combivir^®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

A prospective, 96‐week study of the impact of Trizivir^®, Combivir^®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

In Vitro Suppression of the Lipogenic Pathway by the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz in 3T3 and Human Preadipocytes or Adipocytes

A Randomized Trial of Simplified Maintenance Therapy With Abacavir, Lamivudine, and Zidovudine in Human Immunodeficiency Virus Infection

Contact Info

Product

Resources

About

Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA

Abstract: The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.

Cited by 134 publications

References 18 publications

A prospective, 96‐week study of the impact of Trizivir®, Combivir®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

A prospective, 96‐week study of the impact of Trizivir®, Combivir®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

In Vitro Suppression of the Lipogenic Pathway by the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz in 3T3 and Human Preadipocytes or Adipocytes

A Randomized Trial of Simplified Maintenance Therapy With Abacavir, Lamivudine, and Zidovudine in Human Immunodeficiency Virus Infection

Contact Info

Product

Resources

About

A prospective, 96‐week study of the impact of Trizivir^®, Combivir^®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity

A prospective, 96‐week study of the impact of Trizivir^®, Combivir^®/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral‐naive patients: effect of sex and ethnicity