{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:53:41Z","timestamp":1792785221303,"version":"4.5.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"51","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"crossref","award":["B11-A-14"],"award-info":[{"award-number":["B11-A-14"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"crossref","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Leidos Biomedical, Inc","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}]},{"name":"Leidos Biomedical, Inc","award":["l3XS110"],"award-info":[{"award-number":["l3XS110"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,12,17]]},"abstract":"<jats:p>Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration. We applied this method to lymph node and peripheral blood mononuclear cells from 5 ART-treated donors to determine whether groups of identical subgenomic sequences in the 2 compartments are the result of clonal expansion of infected cells or a viral genetic bottleneck. We found that identical proviral sequences can result from both cellular expansion and viral genetic bottlenecks occurring prior to ART initiation and following ART failure. We identified an expanded T cell clone carrying an intact provirus that matched a variant previously detected by viral outgrowth assays and expanded clones with wild-type and drug-resistant defective proviruses. We also found 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from which we could infer the sequence of the intact parental virus. Thus, MDA-SGS can be used for \u201cviral reconstruction\u201d to better understand intrapatient HIV-1 evolution and to determine the clonality and structure of proviruses within expanded clones, including those with drug-resistant mutations. Importantly, we demonstrate that identical sequences observed by standard SGS are not always sufficient to establish proviral clonality.<\/jats:p>","DOI":"10.1073\/pnas.1910334116","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T18:05:14Z","timestamp":1574877914000},"page":"25891-25899","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors"],"prefix":"10.1073","volume":"116","author":[{"given":"Sean C.","family":"Patro","sequence":"first","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah D.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Bale","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias K.","family":"Halvas","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shao","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wu","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Guo","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Murrell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 65 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Wiegand","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Spindler","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Castle","family":"Raley","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hautman","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Sobolewski","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Fennessey","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shau","family":"Hu","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Luke","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna M.","family":"Hasson","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Niyongabo","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam A.","family":"Capoferri","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2381-1151","authenticated-orcid":false,"given":"Brandon F.","family":"Keele","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Milush","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hoh","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Maldarelli","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Hughes","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Coffin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason W.","family":"Rausch","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Mellors","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F.","family":"Kearney","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1126\/science.1254194","article-title":"HIV latency. 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PLoS Pathog. 13, e1006283 (2017).","journal-title":"PLoS Pathog."},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.cell.2016.06.039","article-title":"Multiple origins of virus persistence during natural control of HIV infection","volume":"166","author":"Boritz E. A.","year":"2016","unstructured":"E. A. Boritz ., Multiple origins of virus persistence during natural control of HIV infection. Cell 166, 1004\u20131015 (2016).","journal-title":"Cell"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/s41591-018-0017-7","article-title":"Clonal CD4+ T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation","volume":"24","author":"Cohn L. B.","year":"2018","unstructured":"L. B. Cohn ., Clonal CD4+ T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation. Nat. Med. 24, 604\u2013609 (2018).","journal-title":"Nat. Med."},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1172\/JCI124291","article-title":"Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy","volume":"129","author":"Einkauf K. B.","year":"2019","unstructured":"K. B. Einkauf ., Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy. J. Clin. Invest. 129, 988\u2013998 (2019).","journal-title":"J. Clin. Invest."},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1084\/jem.20170193","article-title":"Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics","volume":"214","author":"Hosmane N. N.","year":"2017","unstructured":"N. N. Hosmane ., Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics. J. Exp. Med. 214, 959\u2013972 (2017).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1128\/JVI.02139-15","article-title":"Origin of rebound plasma HIV includes cells with identical proviruses that are transcriptionally active before stopping of antiretroviral therapy","volume":"90","author":"Kearney M. F.","year":"2015","unstructured":"M. F. Kearney ., Origin of rebound plasma HIV includes cells with identical proviruses that are transcriptionally active before stopping of antiretroviral therapy. J. Virol. 90, 1369\u20131376 (2015).","journal-title":"J. Virol."},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1172\/JCI120194","article-title":"HIV-1 latent reservoir size and diversity are stable following brief treatment interruption","volume":"128","author":"Salantes D. B.","year":"2018","unstructured":"D. B. Salantes ., HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. J. Clin. Invest. 128, 3102\u20133115 (2018).","journal-title":"J. Clin. Invest."},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1126\/science.1256304","article-title":"HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection","volume":"345","author":"Wagner T. A.","year":"2014","unstructured":"T. A. Wagner ., HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science 345, 570\u2013573 (2014).","journal-title":"Science"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1073\/pnas.1522675113","article-title":"Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo","volume":"113","author":"Simonetti F. R.","year":"2016","unstructured":"F. R. Simonetti ., Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo. Proc. Natl. Acad. Sci. U.S.A. 113, 1883\u20131888 (2016).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"e1006230","DOI":"10.1371\/journal.ppat.1006230","article-title":"Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells","volume":"13","author":"Bui J. K.","year":"2017","unstructured":"J. K. Bui ., Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells. PLoS Pathog. 13, e1006230 (2017).","journal-title":"PLoS Pathog."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"e1004010","DOI":"10.1371\/journal.ppat.1004010","article-title":"Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy","volume":"10","author":"Kearney M. F.","year":"2014","unstructured":"M. F. Kearney ., Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy. PLoS Pathog. 10, e1004010 (2014).","journal-title":"PLoS Pathog."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"6441","DOI":"10.1128\/JVI.00591-06","article-title":"Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells","volume":"80","author":"Bailey J. R.","year":"2006","unstructured":"J. R. Bailey ., Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells. J. Virol. 80, 6441\u20136457 (2006).","journal-title":"J. Virol."},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1073\/pnas.0802203105","article-title":"Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection","volume":"105","author":"Keele B. F.","year":"2008","unstructured":"B. F. Keele ., Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl. Acad. Sci. U.S.A. 105, 7552\u20137557 (2008).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"10627","DOI":"10.1128\/JVI.79.16.10627-10637.2005","article-title":"Effect of a protease inhibitor-induced genetic bottleneck on human immunodeficiency virus type 1 env gene populations","volume":"79","author":"Kitrinos K. M.","year":"2005","unstructured":"K. M. Kitrinos, J. A. Nelson, W. Resch, R. Swanstrom, Effect of a protease inhibitor-induced genetic bottleneck on human immunodeficiency virus type 1 env gene populations. J. Virol. 79, 10627\u201310637 (2005).","journal-title":"J. Virol."},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12977-018-0395-4","article-title":"HIV evolution and diversity in ART-treated patients","volume":"15","author":"van Zyl G.","year":"2018","unstructured":"G. van Zyl, M. J. Bale, M. F. Kearney, HIV evolution and diversity in ART-treated patients. Retrovirology 15, 14 (2018).","journal-title":"Retrovirology"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature14053","article-title":"Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations","volume":"517","author":"Deng K.","year":"2015","unstructured":"K. Deng ., Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517, 381\u2013385 (2015).","journal-title":"Nature"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nm0297-205","article-title":"Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus","volume":"3","author":"Borrow P.","year":"1997","unstructured":"P. Borrow ., Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat. Med. 3, 205\u2013211 (1997).","journal-title":"Nat. Med."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1084\/jem.20090365","article-title":"The first T cell response to transmitted\/founder virus contributes to the control of acute viremia in HIV-1 infection","volume":"206","author":"Goonetilleke N.","year":"2009","unstructured":"N. Goonetilleke .; CHAVI Clinical Core B, The first T cell response to transmitted\/founder virus contributes to the control of acute viremia in HIV-1 infection. J. Exp. Med. 206, 1253\u20131272 (2009).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"10303","DOI":"10.1128\/JVI.01876-15","article-title":"Fitness-balanced escape determines resolution of dynamic founder virus escape processes in HIV-1 infection","volume":"89","author":"Sunshine J. E.","year":"2015","unstructured":"J. E. Sunshine ., Fitness-balanced escape determines resolution of dynamic founder virus escape processes in HIV-1 infection. J. Virol. 89, 10303\u201310318 (2015).","journal-title":"J. Virol."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.chom.2016.04.010","article-title":"What integration sites tell us about HIV persistence","volume":"19","author":"Hughes S. H.","year":"2016","unstructured":"S. H. Hughes, J. M. Coffin, What integration sites tell us about HIV persistence. Cell Host Microbe 19, 588\u2013598 (2016).","journal-title":"Cell Host Microbe"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12977-016-0277-6","article-title":"Retrovirus integration database (RID): A public database for retroviral insertion sites into host genomes","volume":"13","author":"Shao W.","year":"2016","unstructured":"W. Shao ., Retrovirus integration database (RID): A public database for retroviral insertion sites into host genomes. Retrovirology 13, 47 (2016).","journal-title":"Retrovirology"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4049\/jimmunol.142.2.431","article-title":"Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone","volume":"142","author":"Clouse K. A.","year":"1989","unstructured":"K. A. Clouse ., Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J. Immunol. 142, 431\u2013438 (1989).","journal-title":"J. Immunol."},{"key":"e_1_3_4_24_2","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 G. J.","year":"2014","unstructured":"G. J. Besson ., HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy. Clin. Infect. Dis. 59, 1312\u20131321 (2014).","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1101\/gr.180501","article-title":"Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification","volume":"11","author":"Dean F. B.","year":"2001","unstructured":"F. B. Dean, J. R. Nelson, T. L. Giesler, R. S. Lasken, Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification. Genome Res. 11, 1095\u20131099 (2001).","journal-title":"Genome Res."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1038\/nprot.2006.326","article-title":"Whole-genome multiple displacement amplification from single cells","volume":"1","author":"Spits C.","year":"2006","unstructured":"C. Spits ., Whole-genome multiple displacement amplification from single cells. Nat. Protoc. 1, 1965\u20131970 (2006).","journal-title":"Nat. Protoc."},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12977-016-0325-2","article-title":"HIV integration sites in latently infected cell lines: Evidence of ongoing replication","volume":"14","author":"Symons J.","year":"2017","unstructured":"J. Symons ., HIV integration sites in latently infected cell lines: Evidence of ongoing replication. Retrovirology 14, 2 (2017).","journal-title":"Retrovirology"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1128\/JVI.01617-15","article-title":"HIV integration site analysis of cellular models of HIV latency with a probe-enriched next-generation sequencing assay","volume":"90","author":"Sunshine S.","year":"2016","unstructured":"S. Sunshine ., HIV integration site analysis of cellular models of HIV latency with a probe-enriched next-generation sequencing assay. J. Virol. 90, 4511\u20134519 (2016).","journal-title":"J. Virol."},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1002\/cpmc.62","article-title":"Quantification of HIV DNA using droplet digital PCR techniques","volume":"51","author":"Anderson E. M.","year":"2018","unstructured":"E. M. Anderson, F. Maldarelli, Quantification of HIV DNA using droplet digital PCR techniques. Curr. Protoc. Microbiol. 51, e62 (2018).","journal-title":"Curr. Protoc. Microbiol."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1182\/blood-2010-06-288035","article-title":"HIV disease progression correlates with the generation of dysfunctional naive CD8low T cells","volume":"117","author":"Favre D.","year":"2011","unstructured":"D. Favre ., HIV disease progression correlates with the generation of dysfunctional naive CD8low T cells. Blood 117, 2189\u20132199 (2011).","journal-title":"Blood"},{"key":"e_1_3_4_31_2","first-page":"3","article-title":"Enhanced culture assay for detection and quantitation of latently infected, resting CD4+ T-cells carrying replication-competent virus in HIV-1-infected individuals","volume":"304","author":"Siliciano J. D.","year":"2005","unstructured":"J. D. Siliciano, R. F. Siliciano, Enhanced culture assay for detection and quantitation of latently infected, resting CD4+ T-cells carrying replication-competent virus in HIV-1-infected individuals. Methods Mol. 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