Investigating the Effectiveness of Antiretroviral Therapy in sub-Saharan Africa

Gini, J
(2018) Investigating the Effectiveness of Antiretroviral Therapy in sub-Saharan Africa. Doctor of Philosophy thesis, University of Liverpool.

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Antiretroviral therapy (ART) has revolutionised outcomes of HIV infection among people living with HIV (PLWH). But despite these great strides, ongoing concerns of drug-drug interactions, widespread use of herbal medication while using ART, safety in pregnancy and breastfeeding are challenges of HIV treatment in PLWH. Potent new ART are not widely used in most low and middle income countries (LMIC) due to insufficient safety data and fear of adverse events. This Thesis aimed at evaluating the pharmacokinetic (PK) safety of DTG in pregnant and breastfeeding women, drug drug interaction of DTG and Artemisinin Combination Therapy (ACT), and evaluate the factors that affect ART in PLWH such as use of herbal medication among PLWH. Therefore the thesis evaluated the following: Chapter 2 reviewed the clinical PK and pharmacogenetic, drug-drug interactions and safety of DTG in diverse populations from different studies, and concluded that DTG has a variable PK influenced by factors such as food, research conditions and population variability. Chapter 4 evaluated the PK of DTG in 3rd trimester of pregnancy and postpartum women and found no clinically significant difference in DTG PK between pregnancy and postpartum period in women. Safety and efficiency of HIV control was also evaluated and concluded that DTG efficiently control viral load within a short period of time even when women present late in pregnancy. xx Chapter 5 evaluated the drug-drug interaction of DTG and ACT, and concluded that DTG can be co-administered with ACT in treatment of malaria among PLWH on DTG. Chapter 6 evaluated the impact of pharmacogenetics and pregnancy on tenofovir and emtricitabine Pharmacokinetics. An estimated 1-2-fold increase in FTC blood concentration was observed in pregnant and postpartum women with ABCC2 12:g.154962860T>C T allele allele compared to women with CT and CC allele. Sample size was small and was recognise as a limitation. Therefore require verification with larger clinical studies and result should be interpreted with caution. Chapter 7 evaluated the widespread use of herbal medicines amongst PLWH and contamination of herbal medicines with ART in Nigeria as a recognised challenge of ART in sub-Saharan Africa. In conclusion, approximately 2-4% of maternal plasma DTG concentration was excreted in BM, and DTG PK changes were not clinically significant in both pregnancy and postpartum period. DTG Ctrough decreased by 37%, when DTG was administered with AL, 42% when administered with AS-AQ and 24% decrease in AUC0-24 when administered with AS-AQ, but were all above the protein adjusted IC90 for the Ctrough and does not warrant dose adjustment. An estimated 41.8% use of herbal medication was recorded amongst 742 PLWH attending HIV clinics. Herbal use preceded HIV therapy in 38.4% while 14.5% were yet to commence ART. A total of 3 (2%) out of 138 herbal samples evaluated, were contaminated with detectable levels of tenofovir and emtricitabine which is a concern, though implication is unknown.

Item Type: Thesis (Doctor of Philosophy)
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine
Depositing User: Symplectic Admin
Date Deposited: 13 Dec 2019 09:48
Last Modified: 19 Jan 2023 01:06
DOI: 10.17638/03031641