{"id":594,"date":"2008-08-30T18:19:53","date_gmt":"2008-08-30T17:19:53","guid":{"rendered":"http:\/\/localhost\/new\/htb\/?p=594"},"modified":"2013-08-27T16:02:58","modified_gmt":"2013-08-27T16:02:58","slug":"nnrti-resistance-in-infants-prophylaxed-with-single-dose-nevirapine-varies-by-the-timing-of-infection","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/594","title":{"rendered":"NNRTI resistance in infants prophylaxed with single-dose nevirapine varies by the timing of infection"},"content":{"rendered":"<p><strong>Polly Clayden, HIV i-Base<\/strong><\/p>\n<p><strong>Ana Blanco and co-workers from the Mozambique Ministry of Health, Health Alliance International, Seattle, University of Washington, Seattle and Seattle Children&#8217;s Hospital Research Institute showed findings from an evaluation of infants infected with HIV despite receiving single dose nevirapine (sdNVP) prophylaxis.<\/strong><\/p>\n<p>The investigators hypothesised that the timing of nevirapine selective pressure relative to when the HIV first infects infants, effects the selection and persistence of NVP resistant virus. They suggest that:<\/p>\n<ul>\n<li>NVP pressure during &#8220;acute&#8221; (peri-partum) infection will result in transmission or significant selection of mutations that will populate long-lived viral reservoirs and mutations will persist over time.<\/li>\n<li>NVP pressure during &#8220;established&#8221; (in utero) infection will select mutations, however, as HIV-1 reservoirs are already established, fewer will be archived so mutant population will fade over time.<\/li>\n<\/ul>\n<p>This report was from a prospective observational cohort study of 741 infants of whom 100% received single dose NVP (73% mothers). The investigators estimated the timing of infection using nested PCR for HIV-1 pol in dried blood spots, collected by heel stick, at birth and every 2 weeks for the first 2 months of life, and then every 4-8 weeks until one year of age.<\/p>\n<p>Concentrations of resistant virus were determined using quantitative PCR oligonucleotide ligation assays (OLA) for K103N, V106M, Y181C and G190A.<\/p>\n<p>HIV infection was detected by PCR in 53 infants followed between 0-8 weeks of age. 29 were infected in utero (HIV detected at birth), all had wild type virus and 23 had high and stable viral load at birth ie &#8220;established&#8221; infection, and 6 had low viral loads that later increased, suggesting &#8220;acute&#8221; infection at the time of birth.<\/p>\n<p>The investigators reported that the selection and decay of NVP-resistant HIV-1 varied by timing of infection.<\/p>\n<p>Infants with &#8220;established&#8221; infection had frequent selection of NVP-resistant HIV-1 (87%, 95%CI 66-97%).<\/p>\n<p>Postpartum infant AZT+sdNVP vs. NVP decreased NVP-resistant HIV-1 (3\/6 vs. 0\/17, p=0.013). NVP-resistant viruses decayed rapidly compared to infants with peri-partum infection.<\/p>\n<p>Compared to &#8220;established&#8221;, infants with &#8220;acute&#8221; in utero infection (ie low viral load at birth) had infrequent (33%) selection of NVP-resistant HIV-1, p=0.01. In this group of infants NVP-resistant HIV-1 appeared to decay more slowly.<\/p>\n<p>Among infants with peripartum infection (n=24) there was infrequent selection of NVP-resistant HIV-1; (38%, 95%CI 19-59% ) compared to &#8220;established&#8221;, p=0.001. Few infants with NVP-resistance, initially had exclusively wild-type viruses vs. &#8220;established&#8221; (2\/9; 22%, 95%CI 3-60% vs. 21\/21\u00a0; 100%, 95%CI 84-100%), p&lt; 0.001. Also, most infants had 100% NVP-resistant HIV-1 in the first sample with detectable resistance vs. &#8220;established&#8221;, (6\/9; 67%, 95%CI 30-93% vs. 0\/22\u00a0; \u00a00%, 95%CI 0-15%), p&lt; 0.001.<\/p>\n<p>The investigators noted a non-significant trend for less NVP-resistance when mothers did not take sdNVP (0\/5 vs. 9\/19, p= 0.12).<\/p>\n<p>They summarised:<\/p>\n<ul>\n<li>With &#8220;established&#8221; in utero infection, viral replication in utero generates mutations that are selected by sdNVP. AZT appears to reduce the selection of NVP mutations, &#8220;theoretically by increasing the genetic barrier and decreasing viral replication&#8221;. Rapid decay of NVP-resistant virus suggests that after an (undefined) interval, NVP-based HAART may be effective.<\/li>\n<li>With &#8220;acute&#8221; in utero infection there is frequently too little viral replication in utero to generate mutations, so there are no NVP-resistant mutations to select. But if selected NVP-resistant HIV-1 decays slowly suggesting that it populates long-lived reservoirs.<\/li>\n<li>With peri-partum infection, infections with 100% resistant virus suggests transmission of NVP-resistant HIV-1. Persistence of mutations at high concentrations suggests it populates reservoirs. Persistence of mutations suggests that NVP-containing HAART may fail.<\/li>\n<\/ul>\n<p>The investigators noted a low rate of mother-to-child transmission among infants whose mothers received pre-partum AZT in addition to sdNVP. But this was only a minority of women and access needs to be improved.<\/p>\n<p class=\"ref\">Reference:<\/p>\n<p class=\"ref\">Miceck MA, Blanco AJ, Beck IA et al. The selection, transmission and persistence of drug-resistant HIV-1 in infants prophylaxed with single dose nevirapine varies by the timing of infection. XVII IHDRW 2008, Sitges. Abstract 71.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Ana Blanco and co-workers from the Mozambique Ministry of Health, Health Alliance International, Seattle, University of Washington, Seattle and Seattle Children&#8217;s Hospital Research Institute showed findings from an evaluation of infants infected with HIV despite receiving &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,36],"tags":[114],"class_list":["post-594","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-drug-resistance","tag-ihdrw-17th-2008"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/594","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=594"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/594\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=594"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=594"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=594"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}