1.3 Justification
A well-known and significant topic in clinical bacteriology and virology has been the idea of
drug resistance. As far as HIV-1 is concerned, antiviral drug resistance cannot be prevented
that could impair the antiviral effect in individuals infected with HIV-1. Statistics suggest that
more than 50,000 new HIV infections occur yearly (De Cock, Rutherford, & Akhwale, 2014).
ARVT is critical as it helps save lives that could be lost due to the HIV pandemic. ARVT is
voluntary to develop medical safety to reduce death in HIV patients. The use of these tests in
patients with a prescription infection, particularly in regions where the local prevalence of the
primary drug resistance can be understood, should be discussed before initiating care
according to the latest guidelines (Gaolathe, Wirth, Holme, Makhema, Moyo & Chakalisa,
2016). Awareness of the drug resistance profiles and sensitivity trends of naive patients with
HIV-positive nucleoside in developing countries, such as Kenya, is expected to enhance
HIV/AIDS-related services delivery.
1.4 Research Objectives
1.4.1 Main Objective
To profile Nucleoside Reverse Transcriptase Inhibitor drug-resistant and susceptibility
patterns of naive HIV positive patients from Machakos Level 5 hospital.
1.4.2 Specific Objectives
a) To profile resistance to Nucleoside reverse transcriptase inhibitor drugs.
b) To find the markers for resistance to Nucleoside reverse transcriptase inhibitor drugs.
c) To sequence the genetic markers for resistance to Nucleoside reverse transcriptase
inhibitor drugs.
1.5 Significance
This study will help the stakeholders in the ministry of health develop a better plan to see
how to make ARVs work best for the patients. The findings of this study will help understand
the situation in real time and develop a better strategy for managing the phenomenon. It will
also benefit the health ministry to remain outstanding in managing HIV drug resistance. This
study will also add to the literature on HIV drug resistance.
1.5 Definition of Terms
1
, Nucleoside Reverse An Antiretroviral HIV drug class blocks reverse transcriptase
Transcriptase Inhibitor (an HIV enzyme), which the HIV uses to convert RNA into
DNA (reverse transcription).
Drug Resistance This is when a bacteria, virus, or other microorganism changes
form and becomes insensitive to a previously effective drug.
Naive patients These are patients with no previous therapeutic exposure to
HIV.
CHAPTER TWO: - LITERATURE REVIEW
2.1 HIV Epidemiology
Acquired and transmitted antiretroviral drug resistance mutations among persons living with
HIV (PLWH) are a major public health concern, as they can limit the efficacy of available
drugs for the management of HIV. Resistance to antiretroviral (ARV) agents and
subsequently increasing levels of the transmitted, resistant virus have been identified by
many researchers to potentially reverse the substantial gains achieved with potent ART. Both
transmitted drug resistance (TDR) and acquired drug resistance (ADR) reflect the relative
usage of different ARV drugs in the population and the inherent genetic barrier to developing
resistance associated with individual drugs.
HIV is a member of the retroviridae family with two major types, HIV-1 and HIV-2. Human
immunodeficiency virus type 1 is further subdivided into three genetic groups that are M
(major or main), O (outlier), and N (new or non-M or non-O) (Adhiambo et al., 2021;
Adungo et al., 2014). The HIV pandemic viruses are mainly caused by the HIV group M that
are further subdivided into various subtypes. These subtypes include A, B, C, D, F. G, H, J,
and K. These subtypes are further divided by sub-sub types that include A1, A2, A3, F1, and
F2, which are geographically distributed. When two or more subtypes combine, they form
HIV 'circulating recombinant form – CFR' or unique recombinant form (URF), which are
hybrid inter-subtype viral sequences that do not show evidence of onward transmission
(Akhome, 2021).
The development of drug resistance in chronic HIV infection has serious implications. Apart
from the resultant limitations of ineffective treatment regimens, there are also extra cost
implications associated with switches to 2nd or 3rd line therapy and extra demands on
laboratory monitoring of patients. Transmitted or pretreatment HIV drug resistance has a
significant impact on the effectiveness of antiretroviral therapy. It leads to limitations in the
2
A well-known and significant topic in clinical bacteriology and virology has been the idea of
drug resistance. As far as HIV-1 is concerned, antiviral drug resistance cannot be prevented
that could impair the antiviral effect in individuals infected with HIV-1. Statistics suggest that
more than 50,000 new HIV infections occur yearly (De Cock, Rutherford, & Akhwale, 2014).
ARVT is critical as it helps save lives that could be lost due to the HIV pandemic. ARVT is
voluntary to develop medical safety to reduce death in HIV patients. The use of these tests in
patients with a prescription infection, particularly in regions where the local prevalence of the
primary drug resistance can be understood, should be discussed before initiating care
according to the latest guidelines (Gaolathe, Wirth, Holme, Makhema, Moyo & Chakalisa,
2016). Awareness of the drug resistance profiles and sensitivity trends of naive patients with
HIV-positive nucleoside in developing countries, such as Kenya, is expected to enhance
HIV/AIDS-related services delivery.
1.4 Research Objectives
1.4.1 Main Objective
To profile Nucleoside Reverse Transcriptase Inhibitor drug-resistant and susceptibility
patterns of naive HIV positive patients from Machakos Level 5 hospital.
1.4.2 Specific Objectives
a) To profile resistance to Nucleoside reverse transcriptase inhibitor drugs.
b) To find the markers for resistance to Nucleoside reverse transcriptase inhibitor drugs.
c) To sequence the genetic markers for resistance to Nucleoside reverse transcriptase
inhibitor drugs.
1.5 Significance
This study will help the stakeholders in the ministry of health develop a better plan to see
how to make ARVs work best for the patients. The findings of this study will help understand
the situation in real time and develop a better strategy for managing the phenomenon. It will
also benefit the health ministry to remain outstanding in managing HIV drug resistance. This
study will also add to the literature on HIV drug resistance.
1.5 Definition of Terms
1
, Nucleoside Reverse An Antiretroviral HIV drug class blocks reverse transcriptase
Transcriptase Inhibitor (an HIV enzyme), which the HIV uses to convert RNA into
DNA (reverse transcription).
Drug Resistance This is when a bacteria, virus, or other microorganism changes
form and becomes insensitive to a previously effective drug.
Naive patients These are patients with no previous therapeutic exposure to
HIV.
CHAPTER TWO: - LITERATURE REVIEW
2.1 HIV Epidemiology
Acquired and transmitted antiretroviral drug resistance mutations among persons living with
HIV (PLWH) are a major public health concern, as they can limit the efficacy of available
drugs for the management of HIV. Resistance to antiretroviral (ARV) agents and
subsequently increasing levels of the transmitted, resistant virus have been identified by
many researchers to potentially reverse the substantial gains achieved with potent ART. Both
transmitted drug resistance (TDR) and acquired drug resistance (ADR) reflect the relative
usage of different ARV drugs in the population and the inherent genetic barrier to developing
resistance associated with individual drugs.
HIV is a member of the retroviridae family with two major types, HIV-1 and HIV-2. Human
immunodeficiency virus type 1 is further subdivided into three genetic groups that are M
(major or main), O (outlier), and N (new or non-M or non-O) (Adhiambo et al., 2021;
Adungo et al., 2014). The HIV pandemic viruses are mainly caused by the HIV group M that
are further subdivided into various subtypes. These subtypes include A, B, C, D, F. G, H, J,
and K. These subtypes are further divided by sub-sub types that include A1, A2, A3, F1, and
F2, which are geographically distributed. When two or more subtypes combine, they form
HIV 'circulating recombinant form – CFR' or unique recombinant form (URF), which are
hybrid inter-subtype viral sequences that do not show evidence of onward transmission
(Akhome, 2021).
The development of drug resistance in chronic HIV infection has serious implications. Apart
from the resultant limitations of ineffective treatment regimens, there are also extra cost
implications associated with switches to 2nd or 3rd line therapy and extra demands on
laboratory monitoring of patients. Transmitted or pretreatment HIV drug resistance has a
significant impact on the effectiveness of antiretroviral therapy. It leads to limitations in the
2
