GENETIC VARIABILITY AND ANTIRETROVIRAL DRUG RESISTANCE AMONG DRUG-NAÏVE HIV TYPE-1 INFECTED PATIENTS IN KADUNA STATE, NIGERIA
GENETIC VARIABILITY AND ANTIRETROVIRAL DRUG RESISTANCE AMONG DRUG-NAÏVE HIV TYPE-1 INFECTED PATIENTS IN KADUNA STATE, NIGERIA
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Date
2023-06
Authors
TAHIR, Mohammed Ibrahim
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Abstract
An important feature of HIV pandemic is the global genetic diversity of the virus. Emerging HIV
genetic variants results to adverse consequences related to pathogenesis, transmission, diagnosis,
clinical management and vaccine production. Expansion of antiretroviral (ARV) types and
regimens over the last few decades to reduce viral transmission, morbidity and mortality related to
HIV disease has resulted in emergence of transmitted drug resistance which poses serious threat
to the public health. The prevalence of transmitted drug resistance in resource-limited countries is
about 5%, it is however projected to increase with ART expansion. This study was aimed at
determining the viral genetic variability and antiretroviral drug resistance among drug-naïve HIV
type-1 infected patients in Kaduna State, Nigeria. The study was a cross-sectional hospital based
one that adopted the probability proportional to size (PPS) sampling method. Basic demographic
data of each volunteer was captured using structured questionnaire and transcribed to electronic
questionnaire using Epi Info® version 7.2.2.2.6 software. A total of fifty HIV infected drug-naïve
adult participants were enrolled in this study from three voluntary counseling and testing (VCT)
centers in Kaduna State, Nigeria. These participants were tested positive to HIV from April to
October, 2018. The prevalence of HIV-1 was determined using Multispot™ HIV-1/HIV-2 rapid
test kit. The CD4 cell counts and viral load were determined using FACS Flow cytometry and
COBAS® TaqMan® HIV-1 Test respectively. Protease and reverse transcriptase regions of pol gene
were sequenced using Sanger DNA sequencing reaction. Web-based resistance database was used
to analyse the sequence reads. GraphPad Prism version 6.0 was used to analyse the collated data.
Quantitative variables were presented as mean (±SD) and median (IQR), while Spearman
correlation was used to compare the CD4 cell count and viral load. Level of significance of 95%
was adopted to accept or reject null hypothesis at p ≤ 0.05. Socio-demographic data of the study participants were determined. All (100%) the HIV infected participants studied were found to be
infected with HIV type 1. The study population was found to have relatively high median viral
load 158,391 Copies/m with median CD4 cell count of 176 ceel/μL. However, few participants,
despite being ART-naïve, had undetectable plasma viral load. Female had higher CD4 cells count
values and lower plasma HIV-1 viral load value than male. The CD4 cells had strong reciprocal
relationship with the plasma HIV-1 viral load. There was strong negative significant value of
correlation coefficient between HIV-1 plasma viral load and CD4 cells count in the study
population. The prevalence of transmitted drug resistance was found to be 19.5 % which is very
high in the study area. The HIV-1 isolates were characterized into CRF02_AG, subtype G,
CRF06_cpx and subtype C with frequency of 25(61%), 13(32%), 2(5%) and 1(2%) respectively.
A protease inhibitor surveillance drug resistance mutation (SDRM) as M46MI, few other NRTI
and NNRTI SDRM and other polymorphic mutations were detected among the drug-naïve HIV
infected patients. The K103NSG mutation was highest with a frequency of 12.8 % (5/39). Genetic
relatedness of the sequences from the isolates and reference sequences were presented in maximum
likelihood phylogenetic tree. This study indicates that the baseline plasma viral load and CD4 cell
count could affect prognosis, disease progression and transmission. The drug-naïve participants
reported with undetectable plasma RNA could be ‘‘elite’’ controllers. This implies that, the
patients may respond to the currently available highly active antiretroviral therapy (HAART) first
line treatment.
Description
A THESIS SUBMITTED TO THE
SCHOOL OF POSTGRADUATE STUDIES,
AHMADU BELLO UNIVERSITY, ZARIA
IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF
DOCTOR OF PHILOSOPHY (PhD) IN MICROBIOLOGY
DEPARTMENT OF MICROBIOLOGY
FACULTY OF LIFE SCIENCES
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA