GENETIC VARIABILITY AND ANTIRETROVIRAL DRUG RESISTANCE AMONG DRUG-NAÏVE HIV TYPE-1 INFECTED PATIENTS IN KADUNA STATE, NIGERIA

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dc.contributor.authorTAHIR, Mohammed Ibrahim
dc.date.accessioned2024-10-08T09:30:20Z
dc.date.available2024-10-08T09:30:20Z
dc.date.issued2023-06
dc.descriptionA 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
dc.description.abstractAn 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.
dc.identifier.urihttps://kubanni.abu.edu.ng/handle/123456789/13035
dc.language.isoen
dc.titleGENETIC VARIABILITY AND ANTIRETROVIRAL DRUG RESISTANCE AMONG DRUG-NAÏVE HIV TYPE-1 INFECTED PATIENTS IN KADUNA STATE, NIGERIA
dc.typeThesis
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