{"id":4420,"date":"2009-08-22T13:05:34","date_gmt":"2009-08-22T12:05:34","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=4420"},"modified":"2013-08-16T13:18:18","modified_gmt":"2013-08-16T13:18:18","slug":"transmitted-multidrug-resistant-hiv-persists-in-pbmc-dna-for-years","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/4420","title":{"rendered":"Transmitted multidrug-resistant HIV persists in PBMC DNA for years"},"content":{"rendered":"

Mark Mascolini for natap.org<\/strong><\/p>\n

When acquired during primary infection, HIV resistant to the first 3 antiretroviral classes may persist for years in peripheral blood mononuclear cell (PBMC) DNA, according to results of a 5-person substudy<\/strong> [1] in the French PRIMO cohort<\/strong> [2].<\/p>\n

Viral coreceptor use also remained unchanged after primary infection in these people.<\/p>\n

Jade Ghosn (Universite Paris Descartes) and colleagues genotyped HIV and determined coreceptor use in plasma HIV RNA and in HIV DNA extracted from PBMCs of 5 people infected with triple-class-resistant virus and monitored for at least 18 months. After testing primary infection samples, the investigators repeated the analyses at 6 or 12 months, then every 12 months. They defined triple-class resistance as mutations conferring resistance to at least one drug in the first three antiretroviral classes. Ghosn and colleagues determined viral coreceptor use in cellular DNA by a combination of five genotype-based algorithms.<\/p>\n

Five people infected between 1996 and 2006 had virus with the coreceptor preferences and primary resistance mutations in reverse transcriptase (RT) and protease (PRO) detailed in Table 1.<\/p>\n

Patient A began successful therapy 30 months after infection, yet all resistance mutations persisted in PBMC DNA for 78 months (6.5 years), except for K103N, which reverted to wild-type at month 60. Use of the CXCR4 coreceptor remained unchanged in viral DNA to month 78.<\/p>\n

Table 1: Coreceptor use and resistance mutations in 5 patients<\/strong><\/p>\n\n\n\n\n\n\n\n\n
Patient<\/th>\nCoreceptor<\/th>\nRT mutations<\/th>\nProtease mutations<\/th>\n<\/tr>\n
Pt A<\/td>\nCXCR4<\/td>\n41L, 103N, 118I, 210W, 215Y<\/td>\n63P, 90M<\/td>\n<\/tr>\n
Pt B<\/td>\nCCR5<\/td>\n67N, 69N, 70R, 103N, 108I, 116Y, 151M, 184V, 215V, 219Q<\/td>\n10F, 36I, 46I, 82A<\/td>\n<\/tr>\n
Pt C<\/td>\nCXCR4<\/td>\n41L, 67N, 69D, 74V, 115F, 118I, 179V, 184V, I88L, 210W, 215F<\/td>\n10V, 20R, 32I, 33F, 36L, 46I, 47A, 62I, 63P, 71V, 82A, 90M<\/td>\n<\/tr>\n
Pt D<\/td>\nCXCR4<\/td>\n67N, 69N, 70R, 118I, 181C, 215F, 219Q<\/td>\n10I, 20R, 36I, 54V, 82A, 90M<\/td>\n<\/tr>\n
Pt E<\/td>\nCCR5<\/td>\n67N, 69D, 70R, 103N, 184V, 219Q, 225H<\/td>\n10I, 36I, 46L, 53L, 54V, 63P, 71V, 82A<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Patient B began successful therapy and at month 6 genotyping could not be performed in plasma. This patient\u0092s mutation pattern remained unchanged in PBMC DNA through 2 years of follow-up, and the virus continued using CCR5.<\/p>\n

Patient C began successful therapy but had an essentially unchanged mutation pattern in PBMC DNA for 12 months.<\/p>\n

Patient D began treatment soon after diagnosis, and HIV RNA fell to undetectable levels within 6 months. Resistance mutations persisted in HIV DNA and virus remained X4 through 84 months of follow-up.<\/p>\n

Patient E kept the same mutation pattern in HIV RNA and DNA for 36 months after infection, except for the M184V mutation, which reverted to wild-type in HIV RNA at month 12. But M184V persisted in HIV DNA throughout 36 months of follow-up. Coreceptor use did not change from CCR5 in HIV RNA or DNA through month 36.<\/p>\n

Overall, multidrug-resistant virus persisted in these 5 people for a median of 78 months. Ghosn and colleagues proposed that persistence of coreceptor preference in RNA and DNA indicate early expansion of a monoclonal viral population.<\/p>\n

References:<\/p>\n

    \n
  1. Ghosn J, Galimand J, Meyer L, et al. Long-term persistence of resistance mutational pattern and evolution of HIV-tropism in blood plasma and in infected cells of patients who acquired a multidrug-resistant HIV-1 strain at the time of primary infection. XVIII International Drug Resistance Workshop. 9-13 June 2009, Fort Myers, Florida. Abstract 86.<\/li>\n
  2. Chaix ML, Descamps D, Wirden M, et al. Stable frequency of HIV-1 transmitted drug resistance in patients at the time of primary infection over 1996-2006 in France. AIDS. 2009;23:717-724.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Mark Mascolini for natap.org When acquired during primary infection, HIV resistant to the first 3 antiretroviral classes may persist for years in peripheral blood mononuclear cell (PBMC) DNA, according to results of a 5-person substudy [1] in the French PRIMO …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,36],"tags":[115],"class_list":["post-4420","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-drug-resistance","tag-ihdrw-18th-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/4420","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=4420"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/4420\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=4420"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=4420"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=4420"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}