Adverse effects of reverse transcriptase inhibitors

Brinkman, Kees; Hofstede, H.J.M. ter; Burger, David M.; Smeitink, Jan A.M.; Koopmans, P.P.

doi:10.1097/00002030-199814000-00004

Cited by 786 publications

(413 citation statements)

References 81 publications

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“…However, in sensitivity analyses that involved the J-curve assumption, there were rare circumstances when nonhazardous alcohol consumption could extend survival (older individuals with early stage HIV disease and once-weekly nonhazardous alcohol consumption). Nonetheless, it is unclear whether the J curve phenomenon may be generalized to individuals with HIV, who often have multiple comorbidities, less physiological reserve, and therefore may be more susceptible to alcohol-induced injury (Brinkman et al, 1998;Brinkman et al, 1999;Cossarizza et al, 2001;Cote et al, 2002;Bortz, 2002).…”

Section: Discussionmentioning

confidence: 99%

Estimating the impact of alcohol consumption on survival for HIV+ individuals

et al. 2007

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Alcohol consumption is associated with decreased antiretroviral adherence, and decreased adherence results in poorer outcomes. However the magnitude of alcohol's impact on survival is unknown. Our objective was to use a calibrated and validated simulation of HIV disease to estimate the impact of alcohol on survival. We incorporated clinical data describing the temporal and dose-response relationships between alcohol consumption and adherence in a large observational cohort (N = 2,702). Individuals were categorized as nondrinkers (no alcohol consumption), hazardous drinkers (consume ≥5 standard drinks on drinking days), and nonhazardous drinkers (consume <5 standard drinks on drinking days). Our results showed that nonhazardous alcohol consumption decreased survival by more than 1 year if the frequency of consumption was once per week or greater, and by 3.3 years (from 21.7 years to 18.4 years) with daily consumption. Hazardous alcohol consumption decreased overall survival by more than 3 years if frequency of consumption was once per week or greater, and by 6.4 years (From 16.1 years to 9.7 years) with daily consumption. Our results suggest that alcohol is an underappreciated yet modifiable risk factor for poor survival among individuals with HIV.

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Section: Discussionmentioning

confidence: 99%

Estimating the impact of alcohol consumption on survival for HIV+ individuals

et al. 2007

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“…There is a substantial body of experimental evidence that the nucleoside analogue reverse transcriptase inhibitors (NRTIs) affect DNA gamma polymerase, which is involved in mtDNA replication. 9,10 This class affects the mitochondrial gamma polymerase enzyme to varying degrees, with stavudine, ddC, and Zalcitabine (ddC) being the most potent inhibitors of this enzyme, and abacavir, 3TC, and zidovudine the least potent. 9 Many of the adverse effects of this class of antiretroviral agents are postulated to be secondary to mitochondrial toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 This class affects the mitochondrial gamma polymerase enzyme to varying degrees, with stavudine, ddC, and Zalcitabine (ddC) being the most potent inhibitors of this enzyme, and abacavir, 3TC, and zidovudine the least potent. 9 Many of the adverse effects of this class of antiretroviral agents are postulated to be secondary to mitochondrial toxicity. 10 Both patients had evidence of mitochondrial toxicity secondary to nucleoside analogues.…”

Section: Discussionmentioning

confidence: 99%

“…Antiretroviral drugs of the nucleoside analogue class are known to be associated with mitochondrial toxicity, for example, zidovudine can cause a toxic mitochondrial myopathy. [9][10][11] We report two similar cases to describe the severity of the clinical spectrum, and to put this association within the perspective of the relative rarity of the two conditions.…”

Section: Introductionmentioning

confidence: 92%

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Leber's hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus

Mackey

Fingert

Luzhansky

et al. 2003

Eye

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Purpose To describe the clinical features of two cases of Leber's hereditary optic neuropathy (LHON) precipitated by antiretroviral treatment for human immunodeficiency virus (HIV) infection. Methods Two cases of LHON (from an expected four new cases a year throughout Australia) were identified in men on treatment for HIV infection. Results Two HIV-infected men were receiving combination antiretroviral therapy that included nucleoside analogues. Both patients carried the 14 484 mitochondrial DNA mutation and were distantly related (seventh cousins). Although both men presented with sequential visual loss typical of LHON and one had a known close relative affected by LHON, the correct diagnosis was delayed in both cases. The final visual outcome was profoundly reduced in both instances and cessation of antiretroviral therapy did not result in recovery of vision in one patient. Conclusion Patients with a family history of LHON who require antiretroviral treatment should be warned of the high risk of severe visual loss. The underlying mechanism of antiretroviral side effects may help characterize the other trigger factors for LHON.

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“…HIV management also includes dealing with the toxicities of these drugs [27,28,[30][31][32][33], drug-drug interactions, difficulties with the need for 100% adherence [34], lack of long-term efficacy of regimens in real life settings [35][36][37][38][39], cost, co-morbid illnesses such as hepatitis and tuberculosis, opportunistic infections and their prophylaxis, substance abuse, mental illness, and the social situations of patients (housing, nutrition, stigma, family/reproductive counseling, secondary prevention, etc.). Adding to the complexity is the fact that there is no one answer for any of these issues.…”

Section: Key Principles and Complexities Of Antiretroviral Therapymentioning

confidence: 99%

Approaches to antiretroviral therapy in China

Gilliam

Redfield

2005

Cell Res

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China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART) program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3) scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regimens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end, evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences

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Adverse effects of reverse transcriptase inhibitors

Cited by 786 publications

References 81 publications

Estimating the impact of alcohol consumption on survival for HIV+ individuals

Estimating the impact of alcohol consumption on survival for HIV+ individuals

Leber's hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus

Approaches to antiretroviral therapy in China

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