The HIV-1 epidemic in Ethiopia – transmission patterns, antiretroviral drug resistance and treatment outcomes
Assefa, Dawit LU
(2022)
In Lund University, Faculty of Medicine Doctoral Dissertation Series
- Abstract
- A comprehensive understanding of local HIV epidemiology is essential for monitoring transmission, designing, implementing, and evaluating HIV intervention strategies. In paper I, we used a total of 1276 HIV-1 subtype C pol sequences and employed state-of-art phylogenetic and phylodynamic tools to describe the molecular epidemiology of HIV in Ethiopia. Our results showed that the HIV epidemic in Ethiopia resulted from two independent introductions of the founder virus from Eastern Africa and southern African countries in 1975 and 1983, respectively. Our phylodynamic analysis also revealed that the HIV-1 epidemic in Ethiopia manifested expanding growth from its introduction until mid-1990s, followed by a sharp decline in HIV-1... (More)
- A comprehensive understanding of local HIV epidemiology is essential for monitoring transmission, designing, implementing, and evaluating HIV intervention strategies. In paper I, we used a total of 1276 HIV-1 subtype C pol sequences and employed state-of-art phylogenetic and phylodynamic tools to describe the molecular epidemiology of HIV in Ethiopia. Our results showed that the HIV epidemic in Ethiopia resulted from two independent introductions of the founder virus from Eastern Africa and southern African countries in 1975 and 1983, respectively. Our phylodynamic analysis also revealed that the HIV-1 epidemic in Ethiopia manifested expanding growth from its introduction until mid-1990s, followed by a sharp decline in HIV-1 transmissions. The epidemic decline coincided with early behavioral, preventive, and public health awareness campaigns implemented in Ethiopia, a decade before the introduction of antiretroviral therapy (ART) in the country.
Global evidence suggests that the rapid expansion of ART is associated with increase in pretreatment drug resistance (PDR) and acquired drug resistance (ADR), posing threat to both individual outcomes and the prospect of elimination of HIV as a public health threat. We employed WHO-recommended threshold survey method in paper II to assess the transmitted drug resistance (TDR) in Gondar. Our result showed a moderate level of TDR in Gondar, all of which were associated to non-nucleoside reverse transcriptase inhibitor (NNRTI). Our findings also revealed a high rate of HIVDR transmission with the G190A mutation. In paper III, we investigated the emergence of ADR among adults receiving ART in health centers. Our results showed that among 621 individuals, 16.3% had virological failure (VL≥500 copies/mL) at six and/or twelve months, of which 65.3% had ADR. In paper IV, we assessed the prevalence of virological failure, ADR and PDR among female sex workers (FSWs) who participated in the 2014, Ethiopian nationwide biobehavioral survey. PDR was detected in 16.5 % (63/381) FSWs of which 14.4%, 10.5% and 9.2% were associated to NNRTI, nucleoside reverse transcriptase inhibitors (NRTIs), and dual-class, respectively. Among the 239 FSWs on-ART, 59 (24.7%) had virological failure, of which 74.4% had one or more major HIV drug resistance mutations (HIVDRMs). In paper V, we found no dolutegravir-associated HIVDRMs among 460 INSTI-niave (integrase strand transfer inhibitor), participants in the 2017 Ethiopian national HIVDR surveillance, regardless of previous exposure to ART (NNRTIs, NRTIs and/or protease inhibitors). Furthermore, 64.9% of HIV-1 subtype C integrase amino acid positions were conserved (<1.0% variability).
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Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4980efe7-1237-4391-aee8-d269aa254b0e
- author
- Assefa, Dawit
LU
- supervisor
- opponent
-
- Associate Professor Neogi, Ujjwal, Karolinska Institute, Sweden
- organization
- publishing date
- 2022
- type
- Thesis
- publication status
- published
- subject
- keywords
- HIV-1, HIV drug resistance (HIVDR), Phylodynamics, Phylogenetic, Molecular epidemology, transmitted HIVDR, acquired HIVDR, pre-treatment HIVDR, Integrase strand transfer inhibitors (INSTI), Ethiopia, antiretroviral therapy
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2022:105
- pages
- 130 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund
- defense date
- 2022-09-15 13:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-266-3
- language
- English
- LU publication?
- yes
- id
- 4980efe7-1237-4391-aee8-d269aa254b0e
- date added to LUP
- 2022-08-18 15:32:31
- date last changed
- 2022-08-31 09:02:09
@phdthesis{4980efe7-1237-4391-aee8-d269aa254b0e,
abstract = {{A comprehensive understanding of local HIV epidemiology is essential for monitoring transmission, designing, implementing, and evaluating HIV intervention strategies. In paper I, we used a total of 1276 HIV-1 subtype C pol sequences and employed state-of-art phylogenetic and phylodynamic tools to describe the molecular epidemiology of HIV in Ethiopia. Our results showed that the HIV epidemic in Ethiopia resulted from two independent introductions of the founder virus from Eastern Africa and southern African countries in 1975 and 1983, respectively. Our phylodynamic analysis also revealed that the HIV-1 epidemic in Ethiopia manifested expanding growth from its introduction until mid-1990s, followed by a sharp decline in HIV-1 transmissions. The epidemic decline coincided with early behavioral, preventive, and public health awareness campaigns implemented in Ethiopia, a decade before the introduction of antiretroviral therapy (ART) in the country.<br/>Global evidence suggests that the rapid expansion of ART is associated with increase in pretreatment drug resistance (PDR) and acquired drug resistance (ADR), posing threat to both individual outcomes and the prospect of elimination of HIV as a public health threat. We employed WHO-recommended threshold survey method in paper II to assess the transmitted drug resistance (TDR) in Gondar. Our result showed a moderate level of TDR in Gondar, all of which were associated to non-nucleoside reverse transcriptase inhibitor (NNRTI). Our findings also revealed a high rate of HIVDR transmission with the G190A mutation. In paper III, we investigated the emergence of ADR among adults receiving ART in health centers. Our results showed that among 621 individuals, 16.3% had virological failure (VL≥500 copies/mL) at six and/or twelve months, of which 65.3% had ADR. In paper IV, we assessed the prevalence of virological failure, ADR and PDR among female sex workers (FSWs) who participated in the 2014, Ethiopian nationwide biobehavioral survey. PDR was detected in 16.5 % (63/381) FSWs of which 14.4%, 10.5% and 9.2% were associated to NNRTI, nucleoside reverse transcriptase inhibitors (NRTIs), and dual-class, respectively. Among the 239 FSWs on-ART, 59 (24.7%) had virological failure, of which 74.4% had one or more major HIV drug resistance mutations (HIVDRMs). In paper V, we found no dolutegravir-associated HIVDRMs among 460 INSTI-niave (integrase strand transfer inhibitor), participants in the 2017 Ethiopian national HIVDR surveillance, regardless of previous exposure to ART (NNRTIs, NRTIs and/or protease inhibitors). Furthermore, 64.9% of HIV-1 subtype C integrase amino acid positions were conserved (<1.0% variability). <br/><br/>}},
author = {{Assefa, Dawit}},
isbn = {{978-91-8021-266-3}},
issn = {{1652-8220}},
keywords = {{HIV-1, HIV drug resistance (HIVDR), Phylodynamics, Phylogenetic, Molecular epidemology, transmitted HIVDR, acquired HIVDR, pre-treatment HIVDR, Integrase strand transfer inhibitors (INSTI), Ethiopia, antiretroviral therapy}},
language = {{eng}},
number = {{2022:105}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{The HIV-1 epidemic in Ethiopia – transmission patterns, antiretroviral drug resistance and treatment outcomes}},
url = {{https://lup.lub.lu.se/search/files/122810139/Dawit_Assefa_Thesis.pdf}},
year = {{2022}},
}