Key toxicity issues with the WHO-recommended first-line antiretroviral therapy regimen

@article{Mouton2016KeyTI,
  title={Key toxicity issues with the WHO-recommended first-line antiretroviral therapy regimen},
  author={Johannes P Mouton and Karen Cohen and Gary Maartens},
  journal={Expert Review of Clinical Pharmacology},
  year={2016},
  volume={9},
  pages={1493 - 1503}
}
ABSTRACT Introduction: WHO recommends tenofovir, efavirenz, and lamivudine or emtricitabine for first-line antiretroviral therapy (ART) in adults, which replaced more toxic regimens using stavudine, zidovudine or nevirapine. Areas covered: We searched Pubmed to identify observational studies and randomized controlled trials reporting toxicity of these antiretrovirals published between 2011 and 2016, and hand-searched abstracts presented at major HIV conferences in 2015 and 2016, focusing on… 
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References

SHOWING 1-10 OF 148 REFERENCES
Effect of baseline renal function on tenofovir-containing antiretroviral therapy outcomes in Zambia.
  • L. Mulenga, P. Musonda, +8 authors G. Wandeler
  • Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2014
TLDR
TDF use did not attenuate renal function recovery or increase the mortality rate in patients with renal dysfunction, and mortality rates were similar in both treatment groups.
Renal function with use of a tenofovir-containing initial antiretroviral regimen
TLDR
The results support the use of TDF as a component of the initial antiretroviral regimen, and suggest that the eGFR should be monitored more closely when TDF is used with a PI/r.
Tenofovir-induced renal toxicity in 324 HIV-infected, antiretroviral-naïve patients
TLDR
In both the unadjusted and adjusted analyses, tenofovir-exposed subjects had a significantly greater decline in GFR and a significantly higher incidence of proximal tubular dysfunction through 24 months.
Renal Safety of a Tenofovir-Containing First Line Regimen: Experience from an Antiretroviral Cohort in Rural Lesotho
TLDR
In this setting TDF-associated renal toxicity is rare and mainly transient, and further studies to assess TDF safety at lower CrCl thresholds are warranted.
Long-Term Treatment with Tenofovir: Prevalence of Kidney Tubular Dysfunction and Its Association with Tenofovir Plasma Concentration
Background Monitoring of side effects of long-term HIV treatment has become increasingly important. Tenofovir disoproxil fumarate (TDF), a first-line treatment option, is associated with kidney
Investigation of Efavirenz Discontinuation in Multi-ethnic Populations of HIV-positive Individuals by Genetic Analysis
TLDR
Premature discontinuation of ART delays the time to effective long term viral suppression, and is associated with significant morbidity, so pharmacogenetic testing may predict those with a high risk ofEFV discontinuation, and therefore should be considered in patients in whom initiation of EFV based ART is being considered.
Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.
TLDR
The findings do not support the need to restrict TDF use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical and support the use of TDF-containing ART regimens for HIV-infected individuals.
Efavirenz and the CNS: what we already know and questions that need to be answered.
TLDR
This review offers a comprehensive overview of the current evidence on the interaction that efavirenz displays with the CNS, including the penetration and concentration of the drug in the brain, and discusses the prevalence, types and specificities of its side effects.
Clinician compliance with laboratory monitoring and prescribing guidelines in HIV-1-infected patients receiving tenofovir.
TLDR
Kidney function recovered in most patients who continued to receive tenofovir despite a CrCl <50 mL/min, andCreatinine monitoring is feasible where access to laboratory services is good, and further research is needed to determine how best to monitor renal function in resource-limited settings.
Tenofovir effect on the kidneys of HIV-infected patients: a double-edged sword?
TLDR
Rational recommendation for appropriate TDF prescription is concluded, which indicates that TDF is safe for the kidneys even after many years of use.
...
1
2
3
4
5
...