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Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique
Thesis (PhD)--Stellenbosch University, 2025.
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2025
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| access_status_str | Open Access |
| author | Loforte, Nalia Ismael |
| author2 | Preiser, Wolfgang |
| author_browse | Loforte, Nalia Ismael Preiser, Wolfgang |
| author_facet | Preiser, Wolfgang Loforte, Nalia Ismael |
| author_sort | Loforte, Nalia Ismael |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
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Thesis (PhD)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/131804 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:46:13.197Z |
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| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
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| spelling | oai:scholar.sun.ac.za:10019.1/131804 Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique Loforte, Nalia Ismael Preiser, Wolfgang De Oliveira, Tulio Wilkinson, Eduan Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology. HIV (Viruses) -- Molecular aspects -- Mozambique Molecular epidemiology -- Mozambique COVID-19 (Disease) -- Mozambique Phylogeny -- Mozambique RNA viruses -- Genetic aspects UCTD Thesis (PhD)--Stellenbosch University, 2025. ENGLISH ABSTRACT: Background: RNA viruses pose a global health threat because their mutation rates can undermine vaccine efficacy, develop drug resistance and increase transmissibility and disease severity. Globally, viral genome sequencing has become a powerful tool in response to public health threats. Molecular characterization of Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become fundamental in understanding viral dynamics. This dissertation aims to describe the trends of HIV drug resistance (HIVDR) and phylodynamics of SARS-CoV-2 in Mozambique. Methods: Chapters 2 and 3 explore HIVDR surveillance strategies devised by the World Health Organization (WHO) for resource-constrained settings. Eight datasets were analysed for transmitted drug resistance (TDR) and 865 partial pol sequences were generated through Sanger-based sequence technology from recently diagnosed patients between 1999-2018. Pre-treatment (PDR) and acquired drug resistance (ADR) were assessed between 2017-2019, 419 and 409 were antiretroviral therapy (ART) initiators and ART-experienced, respectively. Chapter 4 delves into HIVDR rates and patterns within Gaza province during 2021-2022, focusing on patients switching from non-nucleoside reverse transcriptase inhibitor (NNRTI) to dolutegravir (DTG) based regimens upon confirmation of virological failure (VF). Lastly, Chapter 5 elucidates the dynamics of SARS-CoV-2 introduction and dissemination during the COVID-19 pandemic in Mozambique from samples collected in 10 provinces. Results: TDR for NNRTI increased, from 1.8% 0.6-5.2) in 2002-2004to 12.7% 7.9-19.9) in 2018. High-level PDR for efavirenz (EAT) and nevirapine (NVP) was observed at 13.1% and 16.6%, respectively. Among ART-experienced participants, 56.6% had high-level ADR against WP and ERV, 22.6% had high-level resistance against lamivudine (3TC) and 9.4% against tenofovir disoproxil fumarate (TDF). Furthermore, to investigate DTG HIVDR, we enrolled 717 patients and 69.5% achieved virological suppression after enhanced adherence counselling sessions (EACs). Among those with confirmed VF (n=216), 183 sequences were generated. Intermediate-high DTG resistance was found in 19.6%, (36/183) 13.9-25.4). Among participants with DTG resistance 33.3% (95% Cl: 14.6 - 46.3) showed resistance to all three ARVs in the TLD regimen, 55.6% (95% Cl: 39.3-71.9) to DTG and 3Tcand 11% (95% C': 0.8-21.3) only to DTG. For SARS-CoV-2, 1142 complete viral genomes were obtained and analysed. The Beta, Delta and Omicron variants of concern (VOCs) were responsible for the second, third and fourth epidemic waves, respectively. Most viral introductions were from Southem Africa, particularly South Africa. According to the import/export analysis, the first introduction most likely originated from North America and belonged to Pango lineage 8.1.1. Conclusion: In conclusion, high-level TDR and PDR for NVP and EFV were observed in 2018 supporting the replacement of NNRTls with DTG. Resistance to 3TC in ART-experienced patients observed also suggests special attention to patients who transitioned from NNRT-based regimen to TLD. Intermediate-high DTG resistance was found among those with confirmed VF that transitioned to TLD. This underscores the importance of further research to better understand how pre-existing NRTI resistance in patients transitioning to TLD affects clinical outcomes. Like other countries, genomic surveillance of SARS-CoV-2 in Mozambique was fundamental in understanding the spread and evolution of the VOCs during the pandemic. AFRIKAANSE OPSOMMING: Agtergrond: RNA-virusse verteenwoordig 'n wêreldwye gesondheidsbedreiging omdat hulle teen hoë tempoes muteer, wat die doeltreffendheid van entstowwe kan ondermyn, kan lei tot die ontwikkeling van medikasieweerstandigheid, en die oordraagbaarheid en siektetoestand kan verhoog. Wêreldwyd het die genetika van virale genome 'n kragtige hulpmiddel geword in reaksie op openbare gesondheidsbedreigings. Molekulêre karakterisering van MIV en SARS-CoV-2 het fundamenteel geword om virale dinamika te verstaan. Hierdie tesis het ten doel om tendense van MIV-medikamentweerstandigheid (HIVDR) en die filodinamika van SARS-CoV-2 in Mozambique te beskryf. Metodes: Hoofstukke 2 en 3 ondersoek HIVDR-toesighestrategieë wat deur die WGO vir hulpbronbeperkte omgewings ontwikkel is. Agt datastelle is geanaliseer vir oordraagbare medikasieweerstandigheid (TDR), en 865 gedeeltelike pol-sekwensies is gegenereer deur middel van Sanger-gebaseerde sekwensietegnologie van onlangs gediagnoseerde pasiënte tussen 1999-2018. Voorbehandeling (PDR) en verkryde medikasieresistensie (ADR) is geëvalueer tussen 2017-2019, met onderskeidelik 419 en 409 pasiënte wat antiretrovirale terapie (ART) begin het en ART-ervare pasiënte. Hoofstuk 4 delf in die HIVDR-temas en -patrone binne die Gaza-provinsie gedurende 2021-2022, met 'n fokus op pasiënte wat oorgeskakel het van 'n nie-nukleosied omgekeerde transkripsie-onderdrukker (NNRTI)-gebaseerde regiment na ‘n dolutegravir (DTG)-gebaseerde regiment na bevestiging van virologiese mislukking (VF). Laastens verduidelik Hoofstuk 5 die dinamika van SARS-CoV-2 se oorsprong en verspreiding gedurende die COVID-19-pandemie in Mosambiek, gebaseer op monsters wat van 10 provinsies versamel is. Resultate: TDR vir NNRTI het toegeneem van 1.8% (CI, 0.6-5.2) in 2002-2004 tot 12.7% (CI, 7.9-19.9) in 2018. Hoë vlakke van PDR vir efavirenz (EFV) en nevirapine (NVP) is waargeneem met 13.1% en 16.6% onderskeidelik. Onder ART-ervare pasiënte het 56.6% hoë vlakke van ADR teenoor NVP en EFV gehad, 22.6% het hoë vlakke van weerstand teen lamivudine (3TC) gehad, en 9.4% teen tenofovir disoproxil fumarate (TDF). Verder, om DTG HIVDR te ondersoek, het ons 717 pasiënte ingeskakel, en 69.5% het virologiese onderdrukking bereik na verbeterde nakoming-beradingsessies (EACs). Onder diegene met bevestigde VF (n=216) is 183 sekwensies gegenereer. Tussen-hoë DTG weerstand is in 19.6% gevind (CI: 13.9-25.4). Onder pasiënte met DTG weerstand het 33.3% (95% CI: 14.6 - 46.3) weerstand teen al drie ARVs in die TLD-regime getoon, 55.6% (95% CI: 39.3 - 71.9) teen DTG en 3TC, en 11% (95% CI: 0.8 - 21.3) net teen DTG. Vir SARS-CoV-2 is 1142 volledige virusgenome verkry en geanaliseer. Die Beta, Delta, en Omicron variante van sorg (VOC) was verantwoordelik vir die tweede, derde, en vierde epidemiese golwe, onderskeidelik. Meeste virusinvoere was van Suider-Afrika, veral Suid-Afrika. Volgens die invoer/uitvoer-analise het die eerste invoer waarskynlik uit Noord-Amerika oorsprong en behoort dit aan Pango-afkoms B.1.1. Gevolgtrekking: Ten slotte is hoë vlakke van TDR en PDR vir NVP en EFV in 2018 waargeneem, wat die vervanging van NNRTI's met DTG ondersteun. Weerstand teen 3TC by ART-ervare pasiënte dui ook daarop dat spesiale aandag gegee moet word aan pasiënte wat oorgeskakel van 'n NNRT-gebaseerde regime na TLD. Tussen-hoë DTG weerstand is gevind onder diegene met bevestigde VF wat oorgeskakel het na TLD. Dit beklemtoon die belangrikheid van verdere navorsing om beter te verstaan hoe vooraf bestaande NRTI-weerstand by pasiënte wat oorgaan na TLD kliniese uitkomste beïnvloed. Soos in ander lande, was genoomtoesig van SARS-CoV-2 in Mosambiek fundamenteel om die verspreiding en evolusie van die variante van sorg (VOC) gedurende die pandemie te verstaan. ISISHWANKATHELO: Imvelaphi: Iintsholongwane ze-RNA zibeka isoyikiso kwimpilo yehlabathi ngenxa yamazinga azo oguquko, anokuthi ajongele phantsi ukusebenza kwesitofu sokugonya, akhokelele kuphuhliso lokunganyangeki kumachiza, kwaye anyuse usulelo kunye nobungqongqo bezifo. Ehlabathini lonke, ukulandelelana kwejenome yentsholongwane kuye kwaba sisixhobo esinamandla ekuphenduleni izoyikiso zempilo yoluntu. Ukubonakaliswa kwemolekyuli ye-HIV kunye ne-SARS-CoV-2 ibe sisiseko ekuqondeni amandla entsholongwane. Le dissertation ijolise ekuchazeni iindlela zokunganyangeki ngamachiza e-HIV (HIVDR) kunye ne-phylodynamics ye-SARS-CoV-2 eMozambique. Lindlela: ISahluko sesi-2 nesesi-3 siphonononga izicwangciso-qhinga zokucupha i-HIVDR eziqulunqwe yi-WHO malunga nezicwangciso ezinyanzelwa yizibonelelo. Iiseti zedatha ezisibhozo zihlalutyelwe ukunganyangeki kweziyobisi (TDR), i-865 inxenye yokulandelelana kwe-pol yenziwe ngetekhnoloji yolandelelwano olusekwe kwi-Sanger ukusuka kwizigulana ezisanda kufunyaniswa phakathi kwe-1999-2018. Unyango lwangaphambili (i-PDR) kunye nokufumana ukunganyangeki kweziyobisi (ADR) zavavanywa phakathi kwe-2017-2019, i-419 kunye ne-409 yayiyi-antiretroviral therapy (ART) abaqalisi be-ART-abanamava ngokulandelelana. Isahluko sesi-4 sijonge kumazinga e-HIVDR kunye neepatheni ngaphakathi kwiphondo laseGaza ngo-2021-2022, sigxile kwizigulane ezitshintshayo ukusuka kwi-non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen ukuya kwi-dolutegravir (DTG)-based regimens phezu koqinisekiso lokungaphumeleli kwe-virological (VF). Okokugqibela, iSahluko sesi-5 sicacisa amandla okuziswa kwe-SARS-CoV-2 kunye nokusasazwa ngexesha lobhubhani we-COVID-19 eMozambique kwiisampulu eziqokelelwe kumaphondo ali-10. Iziphumo: I-TDR ye-NNRTI yanda, ukusuka kwi-1.8% (CI, 0.6-5.2) kwi-2002-2004 ukuya kwi-12.7% (CI, 7.9-19.9) ngo-2018. I-PDR ephezulu ye-efavirenz (EFV) kunye nevirapine (NVP) yabonwa kwi-13.1% kunye ne-16.6%, ngokulandelanayo. Phakathi kwabathathi-nxaxheba abanamava e-ART, ama-56.6% ane-ADR ekwinqanaba eliphezulu ngokuchasene ne-NVP ne-EFV, i-22.6% yayinoxhathiso olukwinqanaba eliphezulu ngokuchasene ne-lamivudine (3TC), kunye ne-9.4% ngokuchasene ne-tenofovir disoproxil fumarate (TDF). Ngaphaya koko, ukuphanda nge-DTG HIVDR, sabhalisa izigulane ezingama-717, kwaye ama-69.5% (499/717) afumana ucinezelo lwentsholongwane egazini emva kweeseshini eziphuculweyo zokubambelela kunyango (EACs). Phakathi kwabo bane-VF eqinisekisiweyo (n=216), ii-183 ezilandelelanayo zenziwe. Ukuchasana kwe-DTG okuphakathi kwafunyanwa kwi-19.6%; (36/183) (CI: 13.9-25.4). Phakathi kwabathathi-nxaxheba abanokumelana ne-DTG i-33.3% (12/36) (95% CI: 14.6 - 46.3) ibonise ukuchasana nazo zonke ezintathu ii-ARVs kwirejimeni ye-TLD, i-55.6% (20/36) (95% CI: 39.3 - 71.9) ukuya kwi-DTG kunye ne-3TC, kunye ne-11% (95% CI: 0.8 - 21.3) kuphela kwi-DTG. Kwi-SARS-CoV-2 1142 iigenome zentsholongwane ezipheleleyo zafunyanwa kwaye zahlalutywa. I-Beta, i-Delta, kunye ne-Omicron variants of concern (VOC) babenoxanduva lwesibini, isithathu, kunye nesine samaza obhubhane, ngokulandelanayo. Uninzi lwezintshayelelo zentsholongwane egazini bezisuka kuMazantsi e-Afrika, ngakumbi eMzantsi Afrika. Ngokohlalutyo lokungenisa/ukuthunyelwa ngaphandle, intshayelelo yokuqala kusenokwenzeka ukuba yavela kuMntla Melika kwaye yayiphuma kumnombo wePango B.1.1. Isiphelo: Ukuqukumbela, inqanaba eliphezulu le-TDR kunye ne-PDR ye-NVP kunye ne-EFV yabonwa ngo-2018 ixhasa ukutshintshwa kwe-NNRTIs nge-DTG. Ukunganyangeki kwi-3TC kwizigulane ezinamava e-ART kukwacebisa ingqwalaselo eyodwa kwizigulane ezithe zatshintsha ukusuka kwirejimeni esekwe kwi-NNRT ukuya kwi-TLD. Ukuchasana kwe-DTG okuphakathi kwafunyanwa phakathi kwabo bane-VF eqinisekisiweyo eyatshintshela kwi-TLD. igxininisa ukubaluleka kophando olongezelelweyo ukuqonda ngcono ukuba ukuxhathisa kwe-NRTI ekhoyo ngaphambili kwizigulane ezitshintshela kwi-TLD kuchaphazela njani iziphumo zekliniki. Njengamanye amazwe, ujongo lwe-genomic lwe-SARS-CoV-2 eMozambique lwalubalulekile ekuqondeni ukusasazeka kunye nokuvela kwezinto ezahlukeneyo ezixhalabisayo (VOC) ngexesha lobhubhane. Doctoral 2025-03-27T12:09:43Z 2025-03-27T12:09:43Z 2025-03 Thesis https://scholar.sun.ac.za/handle/10019.1/131804 Stellenbosch University 214 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | HIV (Viruses) -- Molecular aspects -- Mozambique Molecular epidemiology -- Mozambique COVID-19 (Disease) -- Mozambique Phylogeny -- Mozambique RNA viruses -- Genetic aspects UCTD Loforte, Nalia Ismael Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique |
| title | Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique |
| title_full | Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique |
| title_fullStr | Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique |
| title_full_unstemmed | Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique |
| title_short | Phylodynamics and molecular characterization of HIV-1 and SARS-CoV-2 in Mozambique |
| title_sort | phylodynamics and molecular characterization of hiv 1 and sars cov 2 in mozambique |
| topic | HIV (Viruses) -- Molecular aspects -- Mozambique Molecular epidemiology -- Mozambique COVID-19 (Disease) -- Mozambique Phylogeny -- Mozambique RNA viruses -- Genetic aspects UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/131804 |
| work_keys_str_mv | AT lofortenaliaismael phylodynamicsandmolecularcharacterizationofhiv1andsarscov2inmozambique |