{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:02:51Z","timestamp":1780610571488,"version":"3.54.1"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the NIH","award":["ZIA BC 011697"],"award-info":[{"award-number":["ZIA BC 011697"]}]},{"name":"Intramural Research Program of the NIH","award":["U19 AI153217"],"award-info":[{"award-number":["U19 AI153217"]}]},{"name":"Intramural Research Program of the NIH","award":["U01CA200441"],"award-info":[{"award-number":["U01CA200441"]}]},{"name":"Intramural Research Program of the NIH","award":["75N91024F00011"],"award-info":[{"award-number":["75N91024F00011"]}]},{"name":"intramural NCI funding","award":["ZIA BC 011697"],"award-info":[{"award-number":["ZIA BC 011697"]}]},{"name":"intramural NCI funding","award":["U19 AI153217"],"award-info":[{"award-number":["U19 AI153217"]}]},{"name":"intramural NCI funding","award":["U01CA200441"],"award-info":[{"award-number":["U01CA200441"]}]},{"name":"intramural NCI funding","award":["75N91024F00011"],"award-info":[{"award-number":["75N91024F00011"]}]},{"name":"National Institutes of Allergy and Infectious Diseases","award":["ZIA BC 011697"],"award-info":[{"award-number":["ZIA BC 011697"]}]},{"name":"National Institutes of Allergy and Infectious Diseases","award":["U19 AI153217"],"award-info":[{"award-number":["U19 AI153217"]}]},{"name":"National Institutes of Allergy and Infectious Diseases","award":["U01CA200441"],"award-info":[{"award-number":["U01CA200441"]}]},{"name":"National Institutes of Allergy and Infectious Diseases","award":["75N91024F00011"],"award-info":[{"award-number":["75N91024F00011"]}]},{"name":"U.S.\u2013South Africa Program for Collaborative Biomedical Research","award":["ZIA BC 011697"],"award-info":[{"award-number":["ZIA BC 011697"]}]},{"name":"U.S.\u2013South Africa Program for Collaborative Biomedical Research","award":["U19 AI153217"],"award-info":[{"award-number":["U19 AI153217"]}]},{"name":"U.S.\u2013South Africa Program for Collaborative Biomedical Research","award":["U01CA200441"],"award-info":[{"award-number":["U01CA200441"]}]},{"name":"U.S.\u2013South Africa Program for Collaborative Biomedical Research","award":["75N91024F00011"],"award-info":[{"award-number":["75N91024F00011"]}]},{"name":"National Cancer Institute","award":["ZIA BC 011697"],"award-info":[{"award-number":["ZIA BC 011697"]}]},{"name":"National Cancer Institute","award":["U19 AI153217"],"award-info":[{"award-number":["U19 AI153217"]}]},{"name":"National Cancer Institute","award":["U01CA200441"],"award-info":[{"award-number":["U01CA200441"]}]},{"name":"National Cancer Institute","award":["75N91024F00011"],"award-info":[{"award-number":["75N91024F00011"]}]},{"name":"National Cancer Institute, National Institutes of Health, Department of Health and Human Services","award":["ZIA BC 011697"],"award-info":[{"award-number":["ZIA BC 011697"]}]},{"name":"National Cancer Institute, National Institutes of Health, Department of Health and Human Services","award":["U19 AI153217"],"award-info":[{"award-number":["U19 AI153217"]}]},{"name":"National Cancer Institute, National Institutes of Health, Department of Health and Human Services","award":["U01CA200441"],"award-info":[{"award-number":["U01CA200441"]}]},{"name":"National Cancer Institute, National Institutes of Health, Department of Health and Human Services","award":["75N91024F00011"],"award-info":[{"award-number":["75N91024F00011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7\u20139 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the env gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the env gene, &gt;80% contained two or more defects, most commonly stop codons and\/or gag start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and tat was more frequently defective in children. These results suggest that different selection pressures may shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children.<\/jats:p>","DOI":"10.3390\/v17070961","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T15:19:31Z","timestamp":1752247171000},"page":"961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy"],"prefix":"10.3390","volume":"17","author":[{"given":"Jenna M.","family":"Hasson","sequence":"first","affiliation":[{"name":"HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Grace","family":"Katusiime","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-2115","authenticated-orcid":false,"given":"Adam A.","family":"Capoferri","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-1459","authenticated-orcid":false,"given":"Michael J.","family":"Bale","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2777-7376","authenticated-orcid":false,"given":"Brian T.","family":"Luke","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shao","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2559-6034","authenticated-orcid":false,"given":"Mark F.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Stellenbosch University, Cape Town 7500, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3021-5101","authenticated-orcid":false,"given":"Gert","family":"van Zyl","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Stellenbosch University, Cape Town 7500, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7550-6047","authenticated-orcid":false,"given":"Sean C.","family":"Patro","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3839-6576","authenticated-orcid":false,"given":"Mary F.","family":"Kearney","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2024, December 10). Fact Sheet 2024\u2014Latest Global and Regional HIV Statistics on the Status of the AIDS. Available online: https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/UNAIDS_FactSheet_en.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ijid.2020.06.081","article-title":"Horizontal HIV transmission to children of HIV-uninfected mothers: A case series and review of the global literature","volume":"98","author":"Myburgh","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/S0140-6736(04)17140-7","article-title":"Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: A pooled analysis","volume":"364","author":"Newell","year":"2004","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s40121-018-0201-6","article-title":"A Review of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an Aging Population","volume":"7","author":"Chawla","year":"2018","journal-title":"Infect. Dis. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s11904-019-00464-3","article-title":"Aging with HIV","volume":"16","author":"Guaraldi","year":"2019","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/JNC.0000000000000240","article-title":"A Review of Chronic Comorbidities in Adults Living with HIV: State of the Science","volume":"32","author":"Webel","year":"2021","journal-title":"J. Assoc. Nurses AIDS Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/00002030-200304110-00012","article-title":"Maternal health factors and early pediatric antiretroviral therapy influence the rate of perinatal HIV-1 disease progression in children","volume":"17","author":"Abrams","year":"2003","journal-title":"Aids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00002030-200401020-00012","article-title":"Maternal viral load and rate of disease progression among vertically HIV-1-infected children: An international meta-analysis","volume":"18","author":"Ioannidis","year":"2004","journal-title":"Aids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8253","DOI":"10.1128\/JVI.00197-11","article-title":"The genetic bottleneck in vertical transmission of subtype C HIV-1 is not driven by selection of especially neutralization-resistant virus from the maternal viral population","volume":"85","author":"Russell","year":"2011","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00176-20","DOI":"10.1128\/mBio.00176-20","article-title":"Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted\/Founder HIV Variants","volume":"11","author":"Martinez","year":"2020","journal-title":"mBio"},{"key":"ref_11","unstructured":"Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and HHS Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission\u2014A Working Group of the Office of AIDS Research Advisory Council (OARAC) (2024). Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States, Department of Health and Human Services."},{"key":"ref_12","unstructured":"HHS Panel on Antiretroviral Therapy, and Medical Management of Children Living with HIV (2024). Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, Department of Health and Human Services."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1093\/cid\/civ171","article-title":"Impact of the Timing of Initiation of Antiretroviral Therapy During Primary HIV-1 Infection on the Decay of Cell-Associated HIV-DNA","volume":"60","author":"Laanani","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1093\/infdis\/jit311","article-title":"Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size","volume":"208","author":"Jain","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","unstructured":"Hill, A.L., Rosenbloom, D.I., Goldstein, E., Hanhauser, E., Kuritzkes, D.R., Siliciano, R.F., and Henrich, T.J. (2016). Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV. PLoS Pathog., 12.","DOI":"10.1101\/038091"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1097\/QAD.0000000000000178","article-title":"Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children","volume":"28","author":"Ananworanich","year":"2014","journal-title":"Aids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/infdis\/jiu827","article-title":"Early Antiretroviral Therapy in South African Children Reduces HIV-1-Infected Cells and Cell-Associated HIV-1 RNA in Blood Mononuclear Cells","volume":"212","author":"Bedison","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/infdis\/jiu297","article-title":"HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment","volume":"210","author":"Luzuriaga","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e186550","DOI":"10.1172\/jci.insight.186550","article-title":"Profound reduction of HIV-1 reservoir cells over 3 decades of antiretroviral therapy started in early infancy","volume":"10","author":"Vela","year":"2024","journal-title":"JCI Insight"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1001\/jamapediatrics.2014.1560","article-title":"Influence of age at virologic control on peripheral blood human immunodeficiency virus reservoir size and serostatus in perinatally infected adolescents","volume":"168","author":"Persaud","year":"2014","journal-title":"JAMA Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1097\/QAD.0b013e3283553638","article-title":"Dynamics of the resting (CD4+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age","volume":"26","author":"Persaud","year":"2012","journal-title":"Aids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1172\/JCI9006","article-title":"A stable latent reservoir for HIV-1 in resting (CD4+) T lymphocytes in infected children","volume":"105","author":"Persaud","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/cid\/ciu585","article-title":"HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy","volume":"59","author":"Besson","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1086\/504264","article-title":"Long-term decay of the HIV-1 reservoir in HIV-1-infected children treated with highly active antiretroviral therapy","volume":"193","author":"Zanchetta","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e997","DOI":"10.1093\/cid\/ciab143","article-title":"Viral Reservoir in Early-Treated Human Immunodeficiency Virus-Infected Children and Markers for Sustained Viral Suppression","volume":"73","author":"Ajibola","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ijid.2022.11.042","article-title":"HIV-1 reservoir evolution in infants infected with clade C from Mozambique","volume":"127","author":"Koofhethile","year":"2023","journal-title":"Int. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Reeves, D.B., Litchford, M., Fish, C.S., Farrell-Sherman, A., Poindexter, M., Ahmed, N., Cassidy, N.A.J., Neary, J., Wamalwa, D., and Langat, A. (2025). Intact HIV DNA decays in children with and without complete viral load suppression. PLoS Pathog., 21.","DOI":"10.1371\/journal.ppat.1013003"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ofx268","DOI":"10.1093\/ofid\/ofx268","article-title":"Decay of HIV DNA in the Reservoir and the Impact of Short Treatment Interruption in Kenyan Infants","volume":"5","author":"Pankau","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1056\/NEJMoa0800971","article-title":"Early antiretroviral therapy and mortality among HIV-infected infants","volume":"359","author":"Violari","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1172\/JCI94582","article-title":"No evidence of HIV replication in children on antiretroviral therapy","volume":"127","author":"Katusiime","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"jvi.01519-19","DOI":"10.1128\/JVI.01519-19","article-title":"Intact HIV Proviruses Persist in Children Seven to Nine Years after Initiation of Antiretroviral Therapy in the First Year of Life","volume":"94","author":"Katusiime","year":"2020","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.4156","article-title":"Defective proviruses rapidly accumulate during acute HIV-1 infection","volume":"22","author":"Bruner","year":"2016","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.celrep.2017.09.081","article-title":"Identification of Genetically Intact HIV-1 Proviruses in Specific CD(4+) T Cells from Effectively Treated Participants","volume":"21","author":"Hiener","year":"2017","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","article-title":"Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure","volume":"155","author":"Ho","year":"2013","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00568-21","DOI":"10.1128\/mBio.00568-21","article-title":"Early Emergence and Long-Term Persistence of HIV-Infected T-Cell Clones in Children","volume":"12","author":"Bale","year":"2021","journal-title":"mBio"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Botha, J.C., Demirov, D., Gordijn, C., Katusiime, M.G., Bale, M.J., Wu, X., Wells, D., Hughes, S.H., Cotton, M.F., and Mellors, J.W. (2023). The largest HIV-1-infected T cell clones in children on long-term combination antiretroviral therapy contain solo LTRs. mBio, 14.","DOI":"10.1128\/mbio.01116-23"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaax7350","DOI":"10.1126\/scitranslmed.aax7350","article-title":"Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile","volume":"11","author":"Maddali","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_39","unstructured":"National Cancer Institute (2024, May 10). Proviral Sequence Annotation and Intactness Tool, Available online: https:\/\/psd.cancer.gov\/tools\/pvs_annot.php."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","article-title":"A quantitative approach for measuring the reservoir of latent HIV-1 proviruses","volume":"566","author":"Bruner","year":"2019","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/infdis\/jiaa532","article-title":"Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy","volume":"223","author":"Gandhi","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e132997","DOI":"10.1172\/jci.insight.132997","article-title":"Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy","volume":"5","author":"Peluso","year":"2020","journal-title":"JCI Insight"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e0201121","DOI":"10.1128\/jvi.02011-21","article-title":"Plasma-Derived HIV-1 Virions Contain Considerable Levels of Defective Genomes","volume":"96","author":"Fisher","year":"2022","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11892","DOI":"10.1128\/JVI.00932-06","article-title":"Entire genome of a strain of human immunodeficiency virus type 1 with a deletion of nef that was recovered 20 years after primary infection: Large pool of proviruses with deletions of env","volume":"80","author":"Calugi","year":"2006","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e01684-17","DOI":"10.1128\/JVI.01684-17","article-title":"Genetically Intact but Functionally Impaired HIV-1 Env Glycoproteins in the T-Cell Reservoir","volume":"92","author":"Migraine","year":"2018","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Anderson, E.M., Simonetti, F.R., Gorelick, R.J., Hill, S., Gouzoulis, M.A., Bell, J., Rehm, C., P\u00e9rez, L., Boritz, E., and Wu, X. (2020). Dynamic Shifts in the HIV Proviral Landscape During Long Term Combination Antiretroviral Therapy: Implications for Persistence and Control of HIV Infections. Viruses, 12.","DOI":"10.3390\/v12020136"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13100-018-0142-3","article-title":"Variation in proviral content among human genomes mediated by LTR recombination","volume":"9","author":"Thomas","year":"2018","journal-title":"Mob. DNA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1146\/annurev.genet.42.110807.091501","article-title":"Effects of retroviruses on host genome function","volume":"42","author":"Jern","year":"2008","journal-title":"Annu. Rev. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Grandi, N., and Tramontano, E. (2018). Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02039"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8783","DOI":"10.1073\/pnas.1609057113","article-title":"Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy","volume":"113","author":"Imamichi","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.chom.2017.03.008","article-title":"Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, Which Shape the Proviral Landscape","volume":"21","author":"Pollack","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1073\/pnas.1917876117","article-title":"Defective HIV-1 proviruses produce viral proteins","volume":"117","author":"Imamichi","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1146\/annurev.micro.52.1.491","article-title":"The HIV-1 Rev protein","volume":"52","author":"Pollard","year":"1998","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Jayaraman, B., Fernandes, J.D., Yang, S., Smith, C., and Frankel, A.D. (2019). Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-41582-7"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1089\/aid.2024.0029","article-title":"Genetic Characterization of HIV-1 tat Gene from Virologically Controlled Aging Individuals with HIV on Long-Term Antiretroviral Therapy","volume":"41","author":"Kummet","year":"2025","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9506","DOI":"10.1128\/JVI.00650-11","article-title":"The HIV-1 Tat protein has a versatile role in activating viral transcription","volume":"85","author":"Das","year":"2011","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/emboj\/16.6.1224","article-title":"Tat is required for efficient HIV-1 reverse transcription","volume":"16","author":"Harrich","year":"1997","journal-title":"EMBO J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0300-9084(91)90068-C","article-title":"RNA binding by the tat and rev proteins of HIV-1","volume":"73","author":"Karn","year":"1991","journal-title":"Biochimie"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1128\/JVI.02683-10","article-title":"Single-nucleotide changes in the HIV Rev-response element mediate resistance to compounds that inhibit Rev function","volume":"85","author":"Chang","year":"2011","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1073\/pnas.0630530100","article-title":"Rapid evolution of the neutralizing antibody response to HIV type 1 infection","volume":"100","author":"Richman","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/QAD.0b013e328328f76e","article-title":"HIV-1 evolution in gag and env is highly correlated but exhibits different relationships with viral load and the immune response","volume":"23","author":"Piantadosi","year":"2009","journal-title":"Aids"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Troyer, R.M., McNevin, J., Liu, Y., Zhang, S.C., Krizan, R.W., Abraha, A., Tebit, D.M., Zhao, H., Avila, S., and Lobritz, M.A. (2009). Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000365"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.meegid.2007.07.008","article-title":"Selective pressures of human immunodeficiency virus type 1 (HIV-1) during pediatric infection","volume":"7","author":"Leal","year":"2007","journal-title":"Infect. Genet. Evol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1128\/JVI.03608-14","article-title":"HIV-1 fitness cost associated with escape from the VRC01 class of CD4 binding site neutralizing antibodies","volume":"89","author":"Lynch","year":"2015","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bar, K.J., Tsao, C.Y., Iyer, S.S., Decker, J.M., Yang, Y., Bonsignori, M., Chen, X., Hwang, K.K., Montefiori, D.C., and Liao, H.X. (2012). Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002721"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"103615","DOI":"10.1016\/j.isci.2021.103615","article-title":"HIV reservoir quantification using cross-subtype multiplex ddPCR","volume":"25","author":"Cassidy","year":"2022","journal-title":"iScience"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1084\/jem.20190896","article-title":"Combination of quadruplex qPCR and next-generation sequencing for qualitative and quantitative analysis of the HIV-1 latent reservoir","volume":"216","author":"Gaebler","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/clinchem\/hvae192","article-title":"Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay","volume":"71","author":"Delporte","year":"2025","journal-title":"Clin. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e25725","DOI":"10.1002\/jia2.25725","article-title":"HIV-1 proviral landscape characterization varies by pipeline analysis","volume":"24","author":"Ferreira","year":"2021","journal-title":"J. Int. AIDS Soc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/QAD.0000000000001739","article-title":"Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge","volume":"32","author":"Veldsman","year":"2018","journal-title":"Aids"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"White, J.A., Kufera, J.T., Bachmann, N., Dai, W., Simonetti, F.R., Armstrong, C., Lai, J., Beg, S., Siliciano, J.D., and Siliciano, R.F. (2022). Measuring the latent reservoir for HIV-1: Quantification bias in near full-length genome sequencing methods. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010845"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.3390\/v7062760","article-title":"HIV Rev Assembly on the Rev Response Element (RRE): A Structural Perspective","volume":"7","author":"Rausch","year":"2015","journal-title":"Viruses"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/aid.2019.0214","article-title":"HIV Proviral Sequence Database: A New Public Database for Near Full-Length HIV Proviral Sequences and Their Meta-Analyses","volume":"36","author":"Shao","year":"2020","journal-title":"AIDS Res. Hum Retroviruses"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:04Z","timestamp":1760033224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":74,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["v17070961"],"URL":"https:\/\/doi.org\/10.3390\/v17070961","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.05.23.655786","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]}}}