Estudio primario

No clasificado

A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy.

Año 2006
Revista AIDS (London, England)
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BACKGROUND:

Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues.

METHODS:

A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy.

RESULTS:

Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir.

CONCLUSIONS:

Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.

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Estudio primario

No clasificado

Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection.

Año 2003
Revista The New England journal of medicine
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BACKGROUND:

We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved.

METHODS:

We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter.

RESULTS:

At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups.

CONCLUSIONS:

When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.

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Estudio primario

No clasificado

Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine.

Año 2005
Revista AIDS (London, England)
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OBJECTIVE:

To evaluate the 24-month metabolic and morphological benefits obtained from replacing the protease inhibitor (PI) in a regimen with nevirapine, efavirenz or abacavir.

DESIGN AND METHODS:

NEFA was a randomized study designed to compare the efficacy of nevirapine, efavirenz or abacavir as substitutes for PI. A subset of 90 patients [abacavir (n = 29), efavirenz (n = 32), nevirapine (n = 29)] formed the metabolic study. Fasting total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and triglycerides levels were determined. Glucose homeostasis parameters were also collected. Lipodystrophy was evaluated by clinical examination and morphological measurements.

RESULTS:

Treatment simplification led to overall lipid profile improvements. At 24 months, the two non-nucleoside reverse transcriptase inhibitors produced similar lipid benefits: HDL-c levels increased [efavirenz, 15% (P = 0.001); nevirapine, 21% (P < 0.001)] and TC to HDL-c ratios decreased [efavirenz, 14% (P < 0.001); nevirapine, 19% (P < 0.01)], an effect not observed in the abacavir arm. Non-HDL-c levels decreased by 10% in both the abacavir (P = 0.001) and efavirenz (P < 0.05) arms. Significant decreases in the levels of triglycerides occurred for the first year in all treatments; however, at 24 months most of the initial loss had been regained. Patients with baseline moderate or severe lipodystrophy obtained less-pronounced lipid benefits. Several insulin resistance markers showed a trend towards improvement. Conversely, no improvements in morphological abnormalities were observed.

CONCLUSIONS:

Replacing PI with efavirenz, nevirapine or abacavir improved the lipid profile, with more marked results in non-lipodystrophic patients. In contrast, this strategy does not seem to be effective for reversing body fat abnormalities.

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Estudio primario

No clasificado

Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir.

Año 2001
Autores Walli RK , Michl GM , Bogner JR , Goebel FD
Revista European journal of medical research
Enlaces Pubmed

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OBJECTIVE:

To assess the effect of replacing protease inhibitors (PIs) with abacavir on insulin sensitivity and plasma lipids. -

DESIGN:

Pilot study including 31 patients with sustained virological control on their first PI-containing HAART regimen. 16 patients were switched from PIs to abacavir (ABC group), 15 patients continued on PIs (PI group). In all patients, nucleoside-analogue reverse transcriptase inhibitors were continued.

METHODS:

Insulin sensitivity (using an intravenous insulin tolerance test) and fasting total cholesterol and triglycerides were determined at baseline, month 3, 6, 9 and 12.

RESULTS:

In the ABC group, there was a significant increase in median insulin sensitivity from baseline within 6 months (+ 49 micromol/l/min), and a significant decrease in both triglycerides (-41mg/dl) and cholesterol (-40mg/dl) at month 3. These changes were sustained through month 12. In addition, a reversal of baseline insulin resistance, hypercholesterolemia and hypertriglyceridemia was observed in the majority of patients. In the PI group, no significant changes in insulin sensitivity, triglycerides and cholesterol were observed. There was a significant correlation between the changes in insulin sensitivity, triglycerides and cholesterol.

INTERPRETATION:

Switching from PIs to abacavir is associated with an improvement of insulin sensitivity and a decrease of cholesterol and triglycerides in the majority of patients with HAART-associated metabolic alterations and therefore might be an alternative for patients to PI-containing HAART regimens.

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Estudio primario

No clasificado

Genotypic and phenotypic resistance patterns at virological failure in a simplification trial with nevirapine, efavirenz or abacavir.

Año 2005
Revista AIDS (London, England)
Enlaces Pubmed , DOI

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BACKGROUND:

The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors.

OBJECTIVE:

To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms.

METHODS:

Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations.

RESULTS:

Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration).

CONCLUSIONS:

Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.

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Estudio primario

No clasificado

Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: A randomized, 96-week trial

Año 2009
Autores Martin A , Bloch M , Amin J , Baker D , Cooper DA , Emery S - Más
Revista Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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Background: There are 2 once-daily, fixed-dose-combination, dual-nucleoside analogue tablets: tenofovir 300 mg-emtricitabine 200 mg (TDF-FTC) and abacavir 600 mg-lamivudine 300 mg (ABC-3TC). Which fixed-dosecombination tablet is more effective and safe is uncertain. Methods: We compared TDF-FTC and ABC-3TC in a randomized, open-label, 96-week trial in which either fixed-dose-combination was substituted for current nucleoside treatments in human leukocyte antigen-B*5701-negative adults with human immunodeficiency virus loads <50 copies/mL. The primary end point was virological failure (consecutive viral load measurements >400 copies/mL, by intention-to-treat). Secondary end points included death, AIDS, adverse events, serious non-AIDS events, metabolic parameters, and body composition. We used exact statistics for differences in proportions, T tests to compare means, and Cox regression for hazard ratios. Results: Of 441 patients who were screened, 357 were treated; 98% were men, the mean age was 45 years, 30% were receiving TDF, 20% were receiving ABC, and 24% were receiving a protease inhibitor. Virological failure was uncommon (5.6% for ABC-3TC and 3.9% for TDF-FTC; difference, 1.7%; 95% confidence interval [CI], -2.8% to 6.1%; P=.62). No participant developed AIDS, whereas 18 (5%) participants developed a serious non-AIDS event (rate, 2.79 events per 100 person-years; 95% CI, 1.76-4.43), of which 4 were fatal. TDF-FTC was associated with significantly fewer serious non-AIDS events than ABC-3TC (1.2 vs 4.8 events per 100 patientyears; hazard ratio [HR], 0.24; 95% CI, 0.08-0.73; P=.012), influenced mostly by a lower rate of cardiovascular events (0.3 vs 2.2 events per 100 patient-years; HR, 0.12; 95% CI, 0.02-0.98; P=.048). TDF-FTC resulted in significantly lower bone mineral density (mean difference in hip t score, 0.16; 95% CI, 0.08-0.23; P < .001) but not in more fractures. Conclusions: In this population, TDF-FTC and ABC-3TC had similar virological efficacy, but ABC-3TC was associated with more serious non-AIDS events, particularly cardiovascular events. © 2009 by the Infectious Diseases Society of America.

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Estudio primario

No clasificado

Less lipoatrophy and better lipid profile with abacavir as compared to stavudine: 96-week results of a randomized study.

Año 2007
Revista Journal of acquired immune deficiency syndromes (1999)
Enlaces Pubmed , DOI

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OBJECTIVE:

To assess lipoatrophy, other toxicities, and efficacy associated with abacavir as compared with stavudine in HIV-infected antiretroviral-naive patients.

METHODS:

This was a prospective, randomized, open trial, stratified by viral load and CD4 cell count, conducted January 2001 to July 2004. Two hundred thirty-seven adult patients with HIV infection initiating antiretroviral therapy were assigned to receive abacavir (n = 115) or stavudine (n = 122), both combined with lamivudine and efavirenz. The primary endpoint was the proportion of patients with lipoatrophy as assessed by physician and patient observation at 96 weeks.

RESULTS:

A lower proportion of patients assigned to abacavir developed clinical signs of lipoatrophy (4.8% vs. 38.3%; P < 0.001). These observations were confirmed by anthropometric data. Dual energy x-ray absorptiometry (DEXA) scans performed in 57 patients showed significantly greater total limb fat loss in the stavudine arm (-1579 vs. 913 g; P < 0.001). The lipid profile in abacavir patients presented more favorable changes in the levels of triglycerides (P = 0.03), high-density lipoprotein cholesterol (HDLc; P < 0.001), and apolipoprotein A1 (P < 0.001) as well as in the ratio between total cholesterol and HDLc (P = 0.005). Throughout the study, a higher proportion of patients in the stavudine group received lipid-lowering agents as compared to the abacavir group (17% vs. 4%; P = 0.002). Similar virologic and immunologic responses were observed.

CONCLUSIONS:

Assuming the limitations inherent to clinical assessment, this study shows a notably weaker association of abacavir with lipoatrophy than stavudine. DEXA scans and anthropometric measurements supported the clinical findings. In addition, the lipid changes that occurred were more favorable in patients receiving abacavir.

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Revisión sistemática

No clasificado

Diagnostic accuracy of HLA-B*57:01 screening for the prediction of abacavir hypersensitivity and clinical utility of the test: a meta-analytic review.

Año 2014
Revista Pharmacogenomics
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AIM:

To determine diagnostic accuracy of HLA-B*57:01 testing for prediction of abacavir-induced hypersensitivity and to quantify the clinical benefit of pretreatment screening through a meta-analytic review of published studies.

METHODS:

A comprehensive search was performed up to June 2013. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. The pooled diagnostic estimates were calculated using a random effect model.

RESULTS:

Despite the presence of heterogeneity in sensitivity or specificity estimates, the pooled diagnostic odds ratio to detect abacavir-induced hypersensitivity on the basis of clinical criteria was 33.07 (95% CI.: 22.33-48.97, I(2): 13.9%), while diagnostic odds ratio for detection of immunologically confirmed abacavir hypersensitivity was 1141 (95% CI.: 409-3181, I(2): 0%). Pooled analysis of risk ratio showed that prospective HLA-B*57:01 testing significantly reduced the incidence of abacavir-induced hypersensitivity.

CONCLUSION:

This meta-analysis demonstrates an excellent diagnostic accuracy of HLA-B*57:01 testing to detect immunologically confirmed abacavir hypersensitivity and corroborates existing recommendations.

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Estudio primario

No clasificado

Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects.

Año 2005
Revista The Journal of infectious diseases
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BACKGROUND:

Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily.

METHODS:

This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log(10) copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of > or =1.0 log(10) copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions.

RESULTS:

We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log(10) copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from > or =8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P<.001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL.

CONCLUSION:

The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.

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Estudio primario

No clasificado

Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era.

Año 2011
Revista Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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BACKGROUND:

Some studies have suggested that exposure to antiretroviral therapy (ART) with abacavir is associated with an increased risk of acute myocardial infarction (AMI).

METHODS:

Using the Veterans Health Administration's Clinical Case Registry we calculated the risk of AMI and cerebrovascular events (CVA) associated with the cumulative use of abacavir and other nucleoside combinations. We also evaluated the impact of pre-existing chronic kidney disease on the selection of abacavir versus tenofovir in the last recorded ART regimen, and on highly active antiretroviral therapy-associated AMI and CVA risks.

RESULTS:

A total of 19,424 human immunodeficiency virus-infected patients contributed 76,376 patient-years of follow. After adjusting for age, hypercholesterolemia, hypertension, type 2 diabetes, and smoking, the hazard ratio (HR) for each year of abacavir use was 1.18 (95% confidence interval [CI], .92-1.50; P=.191) for AMI and 1.16 (95% CI, .98-1.37; P=.096) for CVA. Abacavir use was more common among patients with prior chronic kidney disease than was tenofovir use (12.46% versus 7.15%; P=.0001), and chronic kidney disease was associated with a significantly higher risk of AMI (HR, 2.41; 95% CI, 1.73-3.36), and CVA (HR, 1.80; 95% CI, 1.44-2.24). Compared with patients who received neither tenofovir nor abacavir, patients who received tenofovir had lower risk of AMI (HR, 0.16; 95% CI, .08-.33; P=.0001) and CVA (HR, 0.22; 95% CI, .15-.32; P=.001). Use of abacavir was associated with lower risk of CVA (HR, 0.60; 95% CI, .45-.79).

CONCLUSIONS:

We observed no association between cumulative or current abacavir use and AMI or CVA. Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA.

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