PHARMACY REVIEW: ANTIRETROVIRALS
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Antiretroviral Therapy – Is 3 a Crowd? There have been huge advances in the pharmacologic treatments of Human Immunodeficiency Virus (HIV) in recent years. It has evolved from a once fatal diagnosis to become a manageable, chronic condition where people living with HIV have a life expectancy that is comparable to those without HIV1. Current antiretroviral (ARV) medication is now more readily available and provides maximal virologic efficacy, yields high genetic barriers to resistance, has more tolerable side effect profiles and a reduced pill burden in comparison to older agents. HIV treatment is instigated to achieve the following goals:
Written by Conor Moran, Infectious Diseases Pharmacist, Mater Misericordiae University Hospital
• HIV RNA suppression • To restore and preserve immunologic function • To reduce HIV-associated morbidity and mortality • To prevent onward transmission2 In 1987, the first drug to treat HIV, Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor (NRTI), was approved to be used as monotherapy. However, it was quickly established that AZT did not maintain viral RNA suppression and therefore lead to the emergence of drug resistance, failure of therapy and patient deterioration3. In the early 1990s research progressed to the idea of treating HIV with three drug regimens, known as “triple therapy”. By targeting different stages of the HIV replication life cycle, “triple therapy” was shown to rapidly
reduce HIV RNA levels, sustain an undetectable viral load and improve patients’ immune function, assessed by means of CD4 lymphocyte count monitoring. Over the past 30 years, antiretroviral therapy has mainly consisted of a two-drug NRTI backbone plus a drug from one other class such as Protease Inhibitors (PI), NonNucleotide Reverse Transcriptase Inhibitors (NNRTI) or Integrase Inhibitors (INI). In the past decade attempts have been made to reduce from three active antiretroviral drugs to two
drug maintenance therapy. The emergence of new antiviral agents with increased viral potency combined with the desire to reduce drug exposure has driven the exploration of dual therapy HIV regimes in recent years. People living with HIV (PLWH) are living longer since the introduction of highly effective three drug antiretroviral therapy. In 2018, 51% of HIV positive Americans were over the age of 504. The Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) Study highlighted
the increasing burden of comorbidities in older people living with HIV (PLWH) in the UK and Ireland5. Lifelong treatment with antiretroviral therapy poses challenges such as polypharmacy and long-term toxicities of ARVs. Drug-drug interactions pose a risk to an ARV regimen by decreasing ARV concentrations by methods such as induction or inhibition of the metabolic pathway, chelation of drug and polyvalent cations or by reduction of stomach acidity. This can lead to loss of treatment efficacy and cause subsequent viral breakthrough. Similarly,
HOSPITALPROFESSIONALNEWS.IE | HPN • AUGUST - 2021
