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The of the reverse transcriptase and protease and

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The aim of this assignment is to
critically appraise an entry from the Paediatric Infectious Disease Journal,
titled Virologic Response to First-line Efavirenz- or
Nevirapine- based Antiretroviral Therapy in HIV-infected African Children (Kekitiinwa
et al. (2017)). This critical appraisal will be done to examine how valid
the results or the trial are, the results themselves and how useful there are
in justifying the research. The study compared drug discontinuation and viral
load in HIV-infected African children following Nevirapine or Efavirenz-based
antiretroviral therapy.

                                                         

Human Immunodeficiency Virus (HIV) is a
Lentivirus within the family of Retroviridae and is thought to have entered the
human population between 1920-1940. The genome consists of two identical single-stranded
RNA molecules that are enclosed within the core of the virus particle. Proviral
DNA is generated by the reverse transcription of the viral RNA genome into DNA,
degradation of the RNA and integration of the double stranded HIV DNA into the
human genome (Blood, 2016).

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HIV is transmitted via bodily fluids,
predominantly blood and semen, with sexual intercourse being the most common
method of transmission worldwide, accounting for approximately 80% of
infections (Askew and Berer, 2003). It
is because of this, that preventative methods such as practising safe sex by
using condoms and abstaining from sharing needles are vital in the prevention of
HIV spread.

 

The treatment of HIV-1 infection was
revolutionised in the mid-1990s by the development of inhibitors of the reverse
transcriptase and protease and the introduction of drug regimens that combined
these agents to enhance overall efficacy and durability of therapy (Arts et al, 2012). Antiretroviral
therapy (ART) has been highly effective in reducing morbidity and mortality of
HIV-patients. There are three classes of antiretroviral drugs;
nucleoside-reverse transcriptase inhibitors (NRTI), non-nucleoside reverse
transcriptase inhibitors (NNRTI) and protease inhibitors. Efavirenz (EFV) and Nevirapine (NVP), both NNRTIs, are two of the most
commonly used medications in first line ART (Mbuagabw et al, 2016).

 

In both developed and developing countries,
combination ART has become one of the most widely used methods of HIV
treatment. Despite an increase in global funding for HIV/AIDS, and considerable
reductions in drug prices, resource limited countries still struggle to
maintain long term therapy options. NNRTI-based ART has been the most
affordable regimen for HIV-infected patients in resource limited countries (Loubiere et al, 2010).

 

SECTION A

Did the trial address a clearly focussed
issue?

Previous literature has noted that NVP
has poorer virologic response in adult and paediatric studies when compared to
EFV, therefore the researchers of this study examined virologic response in 836
previously untreated ART-naïve children aged 3-17 from Uganda and Zimbabwe. They
found that short term VL suppression favoured EFV, but that long term relative
performance was age dependent, with better suppression in older children with
NVP.

 

The trial aimed to compare viral load
(VL) response and drug discontinuation in ART-naïve Ugandan/Zimbabwean children
3-17 years of age initiating ART with clinician chosen EFV or NVP in the ARROW
trial (an open-label randomised trial evaluating two strategic approaches for
management of ART). Predictors of suppression

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