ANTIRETROVIRAL DRUGS

AND THE IMPORTANCE OF

ADHERENCE TO THE DRUGS
BY:
Dr OLASINDE ABDULAZEEZ AYODEJI
Department of Community Medicine, ABUTH Zaria
OUTLINE
• INTRODUCTION
• GOALS OF ARV THERAPY
• CLASSES OF ARV MEDICATIONS
• MODES OF ACTION OF ARV DRUGS
• ADVERSE DRUG REACTTIONS TO ARVs
• FACTORS THAT ENHANCE ADHERENCE TO ARVs
• FACTORS ASSOCIATED WITH POOR ADHERENCE TO ARVs
• STRATEGIES FOR IMPROVING ADHERENCE TO ARVs
INTRODUCTION
• Antiviral drugs are a class of medication used for treating viral infections. Unlike
most antibiotics, antiviral drugs do not destroy their target pathogen; instead they
inhibit its development.
• Antiretroviral drugs are medicatications used for treating HIV infection.
• Antiretroviral therapy (ART) is the treatment of HIV infection using a combination
of antiretroviral drugs (ARVs).
• HAART: Combination of at least 3 or more ARVs from at least 2 different classes to
provide potent and durable therapy.
 Attacks the virus from different directions
 Completely stops viral replication
 Reduces chance of resistance
 Allows for sustained immunological and clinical improvement
INTRODUCTION (contd.)
• HAART also prevents the transmission of HIV between serodiscordant
same sex and opposite sex partners so long as the HIV-positive
partner maintains an undetectable viral load.
• ART should be initiated in all adults including pregnant and
breastfeeding women, adolescents and children living with HIV,
regardless of WHO clinical stage and at any CD4+ cell count.
GOALS OF ARV THERAPY
• The goals of therapy for HIV/AIDS are to provide the optimal and
individualized treatment for individuals infected with HIV at all the stages of
the disease.
• Specifically, the goals are to:
Prolong life
Reduce morbidity
Enhance quality of life
Reduce the transmission of HIV to infants and sexual partners
Maximally suppress plasma HIV RNA (viral load)
Enhance immunity (increase CD4 cell count)
CLASSES OF ARV MEDICATIONS

• Nucleoside/nucleotide reverse transcriptase inhibitors: zidovudine,

abacavir, lamivudine, emtricitabine, stavudine and tenofovir.
• Non-nucleoside reverse transcriptase inhibitors: nevirapine, efavirenz,
etravirine and rilpivirine
• Protease inhibitors: lopinavir, indinavir, nelfinavir, amprenavir,
ritonavir, darunavir, atazanavir.
• Integrase inhibitors: elvitegravir and dolutegravir.
• Entry inhibitors: Maraviroc and enfuvirtide.
MODES OF ACTION OF ARV DRUGS
Entry inhibitors
• Entry inhibitors (or fusion inhibitors) interfere with binding, fusion
and entry of HIV-1 to the host cell by blocking one of several targets.
Maraviroc and enfuvirtide are the two available agents in this class.
MODES OF ACTION OF ARV DRUGS
(contd.)
Nucleoside/nucleotide reverse-transcriptase inhibitors
• Nucleoside reverse-transcriptase inhibitors (NRTI) and nucleotide reverse-
transcriptase inhibitors (NtRTI) are nucleoside and nucleotide analogues
which inhibit reverse transcription by competing with host nucleotides to
serve as the substrate for reverse transcriptase chain elongation.
• Once NRTIs are incorporated into the DNA chain, their lack of a 3' OH
group prevents the subsequent incorporation of other nucleosides. Both
NRTIs and NtRTIs act as competitive substrate inhibitors. Examples of
NRTIs include zidovudine, abacavir, lamivudine, emtricitabine, and of
NtRTIs – tenofovir and adefovir.
MODES OF ACTION OF ARV DRUGS
(contd.)
Non-nucleoside reverse-transcriptase inhibitors
• Non-nucleoside reverse-transcriptase inhibitors (NNRTI) inhibit reverse
transcriptase by binding to an allosteric site of the enzyme; NNRTIs act
as non-competitive inhibitors of reverse transcriptase.
• NNRTIs affect the handling of substrate (nucleotides) by reverse
transcriptase by binding near the active site.
• NNRTIs can be further classified into 1st generation and 2nd generation
NNRTIs. 1st generation NNRTIs include nevirapine and efavirenz. 2nd
generation NNRTIs are etravirine and rilpivirine.
• HIV-2 is naturally resistant to NNRTIs.
MODES OF ACTION OF ARV DRUGS
(contd.)
Integrase inhibitors
• Integrase inhibitors (also known as integrase nuclear strand transfer
inhibitors or INSTIs) inhibit the viral enzyme integrase, which is
responsible for integration of viral DNA into the DNA of the infected
cell.
• They inhibit DNA strand transfer into host-cell genome and thus
prevent viral integration.
• Clinically approved integrase inhibitors are raltegravir, elvitegravir and
dolutegravir.
MODES OF ACTION OF ARV DRUGS
(contd.)
Protease inhibitors
• Protease inhibitors block the viral protease enzyme necessary to
produce mature virions upon budding from the host membrane.
• The inhibit HIV protease by binding to its active site.
• Virus particles produced in the presence of protease inhibitors are
defective and mostly non-infectious. Examples of HIV protease
inhibitors are darunavir, atazanavir, lopinavir, indinavir, nelfinavir,
amprenavir and ritonavir.
ADVERSE DRUG REACTTIONS TO ARVs
• Adverse drug reaction (ADR) is defined by WHO as a response to a
drug which is noxious and unintended, and which occurs at doses
normally used in man for the prophylaxis, diagnosis,or therapy of
disease, or for the modification of physiological function.
• The therapeutic benefits of ARV use far outweigh the risk, thus
despite the ADRs and toxicities encountered with ARV use, they are
still essential in patient management. ADRs that pose a serious threat
to the health and well-being should be discontinued with delay and
necessary consultations made regarding next line of actions.
ADVERSE DRUG REACTTIONS TO ARVs
(contd.)
NRTIs
• The NRTIs can interfere with mitochondrial DNA synthesis and lead to high levels of lactate and lactic
acidosis, liver steatosis, peripheral neuropathy, myopathy and lipoatrophy.
NNRTIs
• NNRTIs are generally safe and well tolerated. Efavirenz may cause neuro-psychiatric effects including
suicidal ideation. Nevirapine can cause severe hepatotoxicity, especially in women with high CD4 counts.
Protease inhibitors
• Protease inhibitors are often given with ritonavir, a strong inhibitor of cytochrome P450 enzymes, leading
to numerous drug-drug interactions. They are also associated with lipodystrophy, elevated triglycerides
and elevated risk of heart attack.
Integrase inhibitors
• Integrase inhibitors (INSTIs) are among the best tolerated of the antiretrovirals with excellent short and
medium term outcomes. Given their relatively new development there is less long term safety data. They
are associated with an increase in creatinine kinase levels and rarely myopathy.
CLASSIFICATION OF ADVERSE DRUG
REACTIONS
• WHO classifies ADRs into four categories based on severity.
FACTORS THAT ENHANCE ADHERENCE
TO ARVs
The following factors have been associated with high adherence rates:
• Increased access to free ART.
• Individual patients, family, peers and friends, community members, or
treatment-supporter engagement in adherence education.
• Family-centered care when more than one family member is infected with HIV.
• Continuous and effective adherence counselling which includes knowledge and
understanding of HIV infection, course of treatment, and expected adverse
reactions and what to do if in the event of an adverse reaction occurring.
• Drug regimen simplicity e.g. Fixed Drug Combination (low pill burden).
• The use of drugs with less adverse effects.
FACTORS ASSOCIATED WITH POOR
ADHERENCE TO ARVs
FACTORS ASSOCIATED WITH POOR
ADHERENCE TO ARVs (contd.)
FACTORS ASSOCIATED WITH POOR
ADHERENCE TO ARVs (contd.)
STRATEGIES FOR IMPROVING
ADHERENCE TO ARVs
STRATEGIES FOR IMPROVING
ADHERENCE TO ARVs (contd.)