{"id":27434,"date":"2014-10-01T12:07:20","date_gmt":"2014-10-01T12:07:20","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=27434"},"modified":"2014-10-06T10:43:30","modified_gmt":"2014-10-06T10:43:30","slug":"case-report-stem-cell-transplantation-from-ccr5-delta-32-homozygous-donor-selects-for-x4-tropic-hiv","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/27434","title":{"rendered":"Case report: Stem cell transplantation from CCR5 delta-32 homozygous donor selects for X4-tropic HIV"},"content":{"rendered":"<p><strong>Richard Jefferys, TAG<\/strong><\/p>\n<p><strong>A letter published yesterday in the New England Journal of Medicine describes the outcome of a recent attempt to repeat the HIV cure achieved in Timothy Brown.<\/strong> [1]<\/p>\n<p>An HIV positive individual requiring stem cell transplantation for the treatment of cancer (anaplastic large-cell lymphoma) was matched with a donor homozygous for the CCR5 delta-32 mutation, which renders cells resistant to CCR5-tropic HIV. Pre-transplant analyses indicated that the majority of HIV in the individual was CCR5-tropic, but there was also evidence of HIV strains capable of entering cells via the CXCR4 (X4) receptor.<\/p>\n<p>Antiretroviral therapy (ART) was interrupted during the transplantation procedure, but restarted afterward due to a viral load rebound to 93,390 copies. Analysis of the rebounding virus revealed the selection of mutations associated with X4-tropism, consistent with this virus gaining a selective advantage after the transplantation of cells resistant to CCR5-tropic HIV. Viral load was successfully re-suppressed by ART for nearly a year until the individual experienced a relapse of the lymphoma.<\/p>\n<p>The relapse necessitated a second ART interruption, leading to a viral load increase to 7,582,496 copies, and the individual died from the cancer shortly afterward. The researchers note the case illustrates that the presence of X4-tropic has the potential to undermine strategies that aim to cure HIV infection by knocking out the CCR5 receptor.<\/p>\n<p>The case report also underscores the importance of monitoring HIV tropism in other research studies looking to provide stem cells from CCR5 delta-32 homozygous donors to HIV positive people requiring transplants for the treatment of cancers.<\/p>\n<p>Two such studies are ongoing in the US: BMT CTN 0903 and IMPAACT P1107.<\/p>\n<p>Source:<br \/>\nTAG basic science blog (28 Aug 2014).<\/p>\n<p>References:<\/p>\n<ol>\n<li>Kordelas L et al. Shift of HIV tropism in stem-cell transplantation with CCR5 delta32 mutation. N Engl J Med 2014; 371:880-882. August 28, 2014. DOI: 10.1056\/NEJMc1405805.<br \/>\n<a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMc1405805\">http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMc1405805<\/a><\/li>\n<li>Allogeneic Transplant in HIV Patients (BMT CTN 0903).<br \/>\n<a href=\"http:\/\/clinicaltrials.gov\/show\/NCT01410344\">http:\/\/clinicaltrials.gov\/show\/NCT01410344<\/a><\/li>\n<li>IMPAACT P1107: Effects of Cord Blood Transplantation With CCR5\u039432 Donor Cells on HIV Persistence<br \/>\n<a href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT02140944\">http:\/\/clinicaltrials.gov\/ct2\/show\/NCT02140944<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Richard Jefferys, TAG A letter published yesterday in the New England Journal of Medicine describes the outcome of a recent attempt to repeat the HIV cure achieved in Timothy Brown. [1] An HIV positive individual requiring stem cell transplantation for &hellip;<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"class_list":["post-27434","post","type-post","status-publish","format-standard","hentry","category-cure-research"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27434","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=27434"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27434\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=27434"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=27434"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=27434"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}