Improvement in Lipoatrophy Associated with Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus–Infected Patients Switched from Stavudine to Abacavir or Zidovudine: The Results of the TARHEEL Study

McComsey, Grace A.; Ward, Douglas J.; Hessenthaler, Siegrid M.; Sension, Michael; Shalit, Peter; Lonergan, J. Tyler; Fisher, Ron; Williams, Vanessa C.; Hernández, Jaime E.

doi:10.1086/380790

Cited by 174 publications

(109 citation statements)

References 15 publications

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“…The positive clinical evolution after substituting TDF or ABV for stavudine was consistent with three studies from high-income countries (including two randomised controlled trials), demonstrating a slow and partial reversal of fat loss. 15,21,22 Only one uncontrolled study addressed the efficacy of substituting stavudine with ZDV or ABV. 15 In that study, some fat recovery was observed with ZDV although less pronounced than with ABV.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the fact that this support programme has had access to TDF and ABV we have been in the unique position of being able to follow patients who were switched to either ZDV or TDF/ABV. There has been only one study in the literature that used both ZDV and ABV for stavudine replacement, 15 but it did not directly compare the efficacy of the drugs and we would like to report on our experience. We previously reported a high level of lipoatrophy amongst patients on stavudine-containing first-line regimens within our antiretroviral treatment (ART) programme in Rwanda, using a standardized questionnaire.…”

Section: Introductionmentioning

confidence: 99%

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Weight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir

Griensven¹,

Zachariah

Rasschaert

et al. 2009

Transactions of the Royal Society of Tropical Medicine and Hygi

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CitationWeight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir. Transactions of the Royal Society of Tropical Medicine and Hygiene (2008) xxx, xxx-xxx a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r h e a l t h . c o m / j o u r n a l s / t r s t Summary This cohort study was conducted amongst female patients manifesting lipoatrophy while receiving stavudine-containing first-line antiretroviral treatment regimens at two urban health centres in Rwanda. The objectives were to assess weight evolution after stavudine substitution and to describe any significant difference in weight evolution when zidovudine or tenofovir/abacavir was used for substitution. All adult patients on stavudine-containing first-line regimens who developed lipoatrophy (diagnosed using a lipodystrophy case definition study-based questionnaire) and whose treatment regimen was changed were included (n = 114). In the most severe cases stavudine was replaced with tenofovir or abacavir (n = 39), and in the remainder with zidovudine (n = 75). For patients changed to zidovudine a progressive weight loss was seen, while those on tenofovir/abacavir showed a progressive weight increase from six months. The between-group difference in weight evolution was significant from nine months (difference at 12 months: 2.3 kg, P = 0.02). These differences were confirmed by follow-up lipoatrophy scores. In multivariate analysis, substitution with tenofovir/abacavir remained significantly associated with weight gain. This is the first study in Africa assessing weight gain as a proxy for recovery after stavudine substitution due to lipoatrophy, providing supporting evidence that tenofovir/abacavir is superior to zidovudine. The weight loss with zidovudine might justify earlier substitution and access to better alternatives like tenofovir/abacavir.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Weight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir

Griensven¹,

Zachariah

Rasschaert

et al. 2009

Transactions of the Royal Society of Tropical Medicine and Hygi

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“…Lipoatrophy can be addressed by switching patients to another NRTI. Switching patients from stavudine to abacavir (preferred) or zidovudine improved fat distribution in HIV-infected patients [46].…”

Section: Lipoatrophymentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.

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“…NRTI switching studies have shown that substituting abacavir for stavudine or zidovudine in patients with clinically apparent lipoatrophy [11,12] is associated with statistically significant improvements in fat wasting. However, absolute increases in limb fat are in the order of 1-2% and are often not apparent to either clinicians or patients, so it would seem prudent to focus on prevention of lipoatrophy, as fat restoration appears to be a slow and possibly incomplete process.…”

Section: Switching Strategies For Lipoatrophymentioning

confidence: 99%

Do Non-Nucleoside Reverse Transcriptase Inhibitors Contribute to Lipodystrophy?

Nolan

2005

Drug Safety

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Abstract:Lipodystrophy complications, including lipoatrophy (pathological fat loss) and metabolic complications, have emerged as important long-term toxicities associated with antiretroviral therapy in the current era. The wealth of data that has accumulated over the past 6 years has now clarified the contribution of specific antiretroviral drugs to the risk of these clinical endpoints, with evidence that lipoatrophy is strongly associated with the choice of nucleoside reverse transcriptase inhibitor therapy (specifically, stavudine and to a lesser extent zidovudine). The aetiological basis of metabolic complications of antiretroviral therapy has proven to be complex, in that the risk appears to be modulated by a number of lifestyle factors that have made the metabolic syndrome highly prevalent in the general population, with additional contributions from HIV disease status itself, as well as from individual drugs within the HIV protease inhibitor class. The currently licensed non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs, efavirenz and nevirapine, have been proven to have a favourable safety profile in terms of lipodystrophy complications. However, it must be noted that NNRTI drugs also have individual toxicity profiles that must be accounted for when considering and/or monitoring their use in the treatment of HIV infection. Full Text:This review will focus specifically on the topic of non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy and its possible association with lipodystrophy complications in patients with HIV. Given the multifactorial nature of the HIV lipodystrophy syndrome, which encompasses a number of complications including lipoatrophy and visceral and/or localised fat accumulation, as well as metabolic complications, it is gratifying to be able to provide a simple negative answer to the question under review here. In short, NNRTI drugs do not contribute to the risk of any component of lipodystrophy--indeed, nevirapine and efavirenz have emerged as having unexpected beneficial effects on lipid profiles, so that they may have a role in the management of metabolic complications that have arisen in the presence of other antiretroviral drugs.However, it remains important to consider the factors that do contribute to the various manifestations of HIV lipodystrophy in order to understand the potential benefits that may be expected with NNRTI therapy. For example, the concept of 'switching' from HIV protease inhibitors (PIs) to NNRTI drugs has been advocated for some time as a potential remedy for lipodystrophy complications. Here, we will examine the evidence suggesting that this strategy may be a rational approach to managing metabolic complications, particularly the atherogenic lipid profile characterised by reduced high-density lipoprotein (HDL)-cholesterol levels, but that lipoatrophy is unlikely to improve in this scenario. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Therapy and LipoatrophyEnormous progress has been made in understanding the 'lipodystrophy syndr...

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Improvement in Lipoatrophy Associated with Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus–Infected Patients Switched from Stavudine to Abacavir or Zidovudine: The Results of the TARHEEL Study

Cited by 174 publications

References 15 publications

Weight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir

Weight evolution in HIV-1 infected women in Rwanda after stavudine substitution due to lipoatrophy: comparison of zidovudine with tenofovir/abacavir

A Review of the Toxicity of HIV Medications

Do Non-Nucleoside Reverse Transcriptase Inhibitors Contribute to Lipodystrophy?

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