{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:50:00Z","timestamp":1764175800556,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia, Portugal","doi-asserted-by":"publisher","award":["LA-REAL\u2014LA\/P\/0117\/2020","GHTM-UID\/04413\/2020"],"award-info":[{"award-number":["LA-REAL\u2014LA\/P\/0117\/2020","GHTM-UID\/04413\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In 2023, the HIV-1 pandemic claimed around 630,000 lives worldwide due to AIDS-related complications. Its burden is significantly heavier in Sub-Saharan Africa, where an increased HIV-1 genetic diversity is common, which increases the risk of resistance to antiretroviral (ARV) drugs. This study aims to update the molecular epidemiology of HIV-1 in Angola, focusing specifically on the gag gene, which is often overlooked, and to assess the potential viability of lenacapavir (LEN)-based ARV therapy in the region. A total of 243 blood samples were collected from ARV-na\u00efve, HIV-infected patients at the General Hospital of Benguela, city of Benguela, Angola. The capsid-encoding region of HIV-1 proviral DNA was amplified by PCR and sequenced. Phylogenetic analysis was performed using the maximum likelihood method, and genome recombinant forms were characterised through bootscanning analysis. Primary resistance mutations to LEN were identified using Stanford University\u2019s HIVdb algorithm. Among the 80 successfully sequenced samples, 13 different genetic forms\/subtypes were identified, with unique recombinant forms (URFs) (37.5%, 30\/80) and subtype C (31.25%, 25\/80) being the most prevalent. Regarding resistance mutations, none were detected, apart from four polymorphic mutations. These findings reinforce Angola\u2019s position as a transitional HIV-1 hotspot between the genetically highly diverse Central Africa and the subtype C-dominated Southern Africa, while also supporting the potential effectiveness of LEN-based regimens for treatment and prevention of HIV-1 infections in the future.<\/jats:p>","DOI":"10.3390\/v17050711","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Diversity in the Capsid Protein-Coding Region of HIV-1 Circulating in Benguela, Angola: Implications for Primary Resistance to the Novel Capsid Inhibitor Lenacapavir"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-9357","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Queir\u00f3s","sequence":"first","affiliation":[{"name":"Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesya","family":"Yefimenko","sequence":"additional","affiliation":[{"name":"Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3421-7833","authenticated-orcid":false,"given":"Filomena M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associated Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-1737","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Piedade","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associated Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","unstructured":"Joint United Nations Programme on HIV\/AIDS (2024). The Urgency of Now: AIDS at a Crossroads, Joint United Nations Programme on HIV\/AIDS."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.molmed.2011.12.001","article-title":"The Origin and Diversity of the HIV-1 Pandemic","volume":"18","author":"Hemelaar","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Afonso, J.M., Bello, G., Guimar\u00e3es, M.L., Sojka, M., and Morgado, M.G. (2012). HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations Among Patients from the North, Central and South Regions of Angola. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042996"},{"key":"ref_4","unstructured":"Quit\u00e9ria, A. (2019). Diversidade Gen\u00e9tica e Resist\u00eancia aos Anti-Retrovirais no V\u00edrus da Imunodefici\u00eancia Humana Tipo 1 em Circula\u00e7\u00e3o em Benguela, Angola. [Master\u2019s Dissertation, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa]."},{"key":"ref_5","unstructured":"(2024, August 20). Country Factsheets\u2014Angola. Available online: https:\/\/www.unaids.org\/en\/regionscountries\/countries\/angola."},{"key":"ref_6","first-page":"48","article-title":"Clinical and Public Health Implications of HIV- Genetic Diversity and Drug Resistance Mutations in Angola: A Systematic Review","volume":"23","author":"Morais","year":"2020","journal-title":"AIDS Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1126\/science.abb4808","article-title":"Structural and Mechanistic Bases for a Potent HIV-1 Capsid Inhibitor","volume":"370","author":"Bester","year":"2020","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhuang, S., and Torbett, B.E. (2021). Interactions of HIV-1 Capsid with Host Factors and Their Implications for Developing Novel Therapeutics. Viruses, 13.","DOI":"10.3390\/v13030417"},{"key":"ref_9","unstructured":"National Institutes of Health (2021). Gilead Sciences Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in Human Immunodeficiency Virus (HIV) -1 Infected Adults."},{"key":"ref_10","unstructured":"National Institutes of Health (2024). Gilead Sciences Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination with an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living with HIV-1 Infection with Multidrug Resistance (CAPELLA)."},{"key":"ref_11","unstructured":"Margot, N. (2023, January 18\u201321). Resistance Analysis of Long-Acting Lenacapavir in Heavily Treatment-Experienced People with HIV After 104 Weeks of Treatment. Proceedings of the 19th European AIDS Conference, Warsaw, Poland."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/jac\/dkab503","article-title":"Phenotypic Resistance to Lenacapavir and Monotherapy Efficacy in a Proof-of-Concept Clinical Study","volume":"77","author":"Margot","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/jac\/dkac388","article-title":"Evaluation of HIV-1 Capsid Genetic Variability and Lenacapavir (GS-6207) Drug Resistance-Associated Mutations According to Viral Clades Among Drug-Naive Individuals","volume":"78","author":"Nka","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Troyano-Hern\u00e1ez, P., Reinosa, R., and Holgu\u00edn, \u00c1. (2022). HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.854974"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e29292","DOI":"10.1002\/jmv.29292","article-title":"Rapid HIV-1 Genotyping Assay for the Detection of Capsid Mutations","volume":"95","author":"Margot","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_16","first-page":"95","article-title":"BioEdit: A User-Friendly Biological Sequence Alignment Editor and Analysis Program for Windows 95\/98\/NT","volume":"41","author":"Hall","year":"1999","journal-title":"Nucleic Acids Symp. Ser."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic Local Alignment Search Tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1093\/bib\/bbx108","article-title":"MAFFT Online Service: Multiple Sequence Alignment, Interactive Sequence Choice and Visualization","volume":"20","author":"Katoh","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D67","DOI":"10.1093\/nar\/gkv1276","article-title":"GenBank","volume":"44","author":"Clark","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/oxfordjournals.molbev.a026334","article-title":"Selection of Conserved Blocks from Multiple Alignments for Their Use in Phylogenetic Analysis","volume":"17","author":"Castresana","year":"2000","journal-title":"Mol. Biol. Evol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W232","DOI":"10.1093\/nar\/gkw256","article-title":"W-IQ-TREE: A Fast Online Phylogenetic Tool for Maximum Likelihood Analysis","volume":"44","author":"Trifinopoulos","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/JVI.73.1.152-160.1999","article-title":"Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination","volume":"73","author":"Lole","year":"1999","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1086\/503914","article-title":"Web Resources for HIV Type 1 Genotypic-Resistance Test Interpretation","volume":"42","author":"Liu","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9068","DOI":"10.1128\/JVI.00340-15","article-title":"HIV-1 Resistance to the Capsid-Targeting Inhibitor PF74 Results in Altered Dependence on Host Factors Required for Virus Nuclear Entry","volume":"89","author":"Zhou","year":"2015","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1128\/JVI.01406-10","article-title":"Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Infection by Virus Capsid Destabilization","volume":"85","author":"Shi","year":"2011","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sowd, G.A., Shi, J., Fulmer, A., and Aiken, C. (2023). HIV-1 Capsid Stability Enables Inositol Phosphate-Independent Infection of Target Cells and Promotes Integration into Genes. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011423"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.meegid.2013.04.032","article-title":"Automated Subtyping of HIV-1 Genetic Sequences for Clinical and Surveillance Purposes: Performance Evaluation of the New REGA Version 3 and Seven Other Tools","volume":"19","author":"Faria","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1038\/s41467-019-10884-9","article-title":"Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART","volume":"10","author":"Bachmann","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Abidi, S.H., Aibekova, L., Davlidova, S., Amangeldiyeva, A., Foley, B., and Ali, S. (2021). Origin and Evolution of HIV-1 Subtype A6. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260604"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"de Pina-Araujo, I.I.M., Delatorre, E., Guimar\u00e3es, M.L., Morgado, M.G., and Bello, G. (2015). Origin and Population Dynamics of a Novel HIV-1 Subtype G Clade Circulating in Cape Verde and Portugal. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127384"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.meegid.2008.04.001","article-title":"Different Sliding Window Sizes and Inappropriate Subtype References Result in Discordant Mosaic Maps and Breakpoint Locations of HIV-1 CRFs","volume":"8","author":"Zhang","year":"2008","journal-title":"Infect. Genet. Evol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1128\/JVI.03014-13","article-title":"Identifying Recombination Hot Spots in the HIV-1 Genome","volume":"88","author":"Smyth","year":"2014","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Da Silva, R.K.M., Morais, J., Foley, B.T., Bello, G., Morgado, M.G., and Guimar\u00e3es, M.L. (2022). Identification of a New Circulating Recombinant Form of Human Immunodeficiency Virus Type 1, CRF124_cpx Involving Subtypes A, G, H, and CRF27_cpx in Angola. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.992640"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13596535231220754","DOI":"10.1177\/13596535231220754","article-title":"Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA","volume":"28","author":"Margot","year":"2023","journal-title":"Antivir. Ther."},{"key":"ref_35","unstructured":"Yant, S.R. (2019, January 21\u201324). In Vitro Resistance Profile of GS-6207, a First-in-Class Picomolar HIV Capsid Inhibitor in Clinical Development as a Novel Long-Acting Antiretroviral Agent. Proceedings of the 10th IAS Conference on HIV Science (IAS 2019), Mexico City, Mexico."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/COH.0000000000000534","article-title":"HIV Subtype Diversity Worldwide","volume":"14","author":"Bbosa","year":"2019","journal-title":"Curr. Opin. HIV AIDS"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/5\/711\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:45Z","timestamp":1760031225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/5\/711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["v17050711"],"URL":"https:\/\/doi.org\/10.3390\/v17050711","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2025,5,16]]}}}