{"id":50971,"date":"2025-04-21T15:09:51","date_gmt":"2025-04-21T15:09:51","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=50971"},"modified":"2025-06-01T22:42:33","modified_gmt":"2025-06-01T22:42:33","slug":"the-rio-study-qa-about-controlling-hiv-with-bnabs","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/50971","title":{"rendered":"The RIO study: Q&#038;A about controlling HIV with bNAbs"},"content":{"rendered":"<p><a href=\"https:\/\/i-base.info\/htb\/wp-content\/uploads\/2025\/03\/RIO-for-website-Ash-sized.png\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-50562 size-full\" src=\"https:\/\/i-base.info\/htb\/wp-content\/uploads\/2025\/03\/RIO-for-website-Ash-sized.png\" alt=\"\" width=\"1206\" height=\"467\" srcset=\"https:\/\/i-base.info\/htb\/wp-content\/uploads\/2025\/03\/RIO-for-website-Ash-sized.png 1206w, https:\/\/i-base.info\/htb\/wp-content\/uploads\/2025\/03\/RIO-for-website-Ash-sized-300x116.png 300w, https:\/\/i-base.info\/htb\/wp-content\/uploads\/2025\/03\/RIO-for-website-Ash-sized-1024x397.png 1024w, https:\/\/i-base.info\/htb\/wp-content\/uploads\/2025\/03\/RIO-for-website-Ash-sized-768x297.png 768w\" sizes=\"auto, (max-width: 1206px) 100vw, 1206px\" \/><\/a><\/p>\n<p><strong>Simon Collins, HIV i-Base<\/strong><\/p>\n<p><strong>This Q&amp;A is about the RIO study and using immune-based treatments as part of HIV cure-related research.<\/strong><\/p>\n<h2>Background<\/h2>\n<p><strong>In March 2025, the first results from the RIO study were presented at CROI. [1-4]<\/strong><\/p>\n<p>The results showed that immune-based treatments called bNAbs could keep viral load undetectable without HIV meds (ART).<\/p>\n<p>RIO also showed that in some people bNAbs can also work like an HIV vaccine. Some people responded so well that they have not needed ART for over a year. These early results are exciting, but we need to see how long this response lasts.<\/p>\n<p>We also need to understand why the bNAbs only worked for some people and not others.<\/p>\n<p>Similar results were also reported in South African women in a study called FRESH. [5, 6]<\/p>\n<h2>What is the RIO study?<\/h2>\n<p><strong>RIO is an HIV study using immune-based treatments. These immune treatments are called bNAbs (pronounced bee-nabs).<\/strong><\/p>\n<p>The two bNAbs are long-acting 10-1074 and 3BNC117, also called zinlirvimab (ZAB) and teropavimab (TAB).<\/p>\n<p>RIO involved stopping HIV meds after being given the bNAbs. The time off-ART is called an ATI which stands for analytic treatment interruption.<\/p>\n<p>The ATI showed that the bNAbs worked very well for some people but not for others.<\/p>\n<p>The results were one of the most important studies presented at a leading HIV conference called CROI, held in March 2025.<\/p>\n<h2>Who took part in RIO?<\/h2>\n<p><strong>RIO enrolled 68 men who had been diagnosed in early HIV infection and who started early ART. This included:<\/strong><\/p>\n<ul>\n<li>Being diagnosed within about six months of becoming HIV positive.<\/li>\n<li>Having started ART during very early infection.<\/li>\n<li>Having an undetectable viral load on ART for at least six months.<\/li>\n<li>Being sensitive to the bNAbs.<\/li>\n<li>Not having active hepatitis B.<\/li>\n<li>Agreeing to take part in the ATI.<\/li>\n<\/ul>\n<h2>Why were no women included?<\/h2>\n<p><strong>RIO was also open to women, but in the UK women tend to be diagnosed later in infection.<\/strong><\/p>\n<p>The FRESH study enrolled 20 women from Southern Africa. [5]<\/p>\n<p>See below for more information.<\/p>\n<h2>What did the RIO study involve?<\/h2>\n<p><strong>Study participants were also tested to check that the bNAbs were likely to work.<\/strong><\/p>\n<ul>\n<li>They were then randomised to one of two groups. One group received active bNAbs. The other group received a non-active placebo infusion.<\/li>\n<li>ART was also stopped.<\/li>\n<li>Close monitoring included viral load tests every week.<\/li>\n<li>ART was then restarted after viral load reached a certain level. This was after either being above 1,000 copies\/mL for more than 6 weeks or confirmed at above 100,000 copies\/mL.<\/li>\n<li>People in the placebo group then had the chance to use the active bNAbs after their viral load rebounded. They stayed on ART for another six months and then took a second ATI.<\/li>\n<\/ul>\n<h2>What were the main results from RIO?<\/h2>\n<p><strong>Several important results were presented at CROI.<\/strong><\/p>\n<ul>\n<li>Most people in the placebo group had viral load rebound within a few weeks. Only 3 out of 34 people were still undetectable off-ART at week 20.<\/li>\n<li>Most people in the active group stayed undetectable for over five months. In this group 25 out of 34 people were still off-ART.<\/li>\n<li>Access to bNAbs reduced the chance of viral load rebounding by more than 90%. The difference between the two groups was extremely significant, (p &lt;0.0001).<\/li>\n<li>About 1 in 3 people in the active group (13 out of 34) continued to stay off-ART for 48 weeks and 7 of these 13 were still off-ART after 18 months. By this time there would be no active bNAbs left in their body to reduce viral load. This is important.<\/li>\n<li>Some people in the active group continued to have undetectable viral load for much longer than a year. This is also important.<\/li>\n<li>There were three main responses to bNAbs during the ATI:<br \/>\n<span>(1) Rapid viral rebound &#8211; within a few weeks.<br \/>\n<\/span><span>(2) Slow viral rebound &#8211; roughly 16 to 48 weeks.<br \/>\n<\/span><span>(3) Viral load remained undetectable throughout.<\/span><\/li>\n<li>People who had the longest responses to the bNAbs developed stronger immune responses against HIV.<\/li>\n<li>One person in the active group, had viral rebound after the ATI, but they then became undetectable again without needing ART. This person showed a potential vaccine-like response to the bNAbs. They have now been off-ART for more than 18 months.<\/li>\n<li>Two people in the placebo group also stayed undetectable for more than a year. This type of response has been reported in earlier studies too. It shows why the study needed to have a control group.<\/li>\n<\/ul>\n<h2>Who had the strongest vaccine-like response?<\/h2>\n<p><strong>The person with the vaccine-like response was a 38-year-old man who was diagnosed in 2017 with viral load of 55,000 copies\/mL. He started ART within three weeks.<\/strong><\/p>\n<p>Several years later he joined the RIO study where he was randomised to the placebo group.<\/p>\n<p>After four weeks into the first ATI his viral load rebounded to 6225 copies\/mL. He then received dual bNAbs and restarted ART for 6 months before a second ATI. This time viral load rebounded after five weeks and remained detectable for 20 weeks but only at low levels (peak 1893 copies\/mL).<\/p>\n<p>Viral load then became undetectable to &lt;20 copies\/mL and remained this low for 80 weeks. During this time, levels of both bNAbs were too low to be active and HIV couldn&#8217;t be detected.<\/p>\n<p>Technically, if this person remains undetectable and researchers cannot find HIV in his body, could this be a cure?<\/p>\n<h2>Has this person been cured?<\/h2>\n<p><strong>Researchers are generally careful and cautious. Even after such a strong immune response it is important to see how long this person stays undetectable.<\/strong><\/p>\n<p>HIV might still be hiding somewhere in this person. If these cells wake after the vaccine-like response has stopped, then viral load might still rebound.<\/p>\n<p>Other types of cure studies, including stem cell transplants, have waited for several years before calling the results a cure. Even then, some researchers prefer to use the word remission.<\/p>\n<p>Stem cell transplants are extremely dangerous though and are only used with untreatable cancer.<\/p>\n<p>RIO used immune-based treatments that are very safe and that could be used by everyone. We still need to see how long the response will last.<\/p>\n<h2>What do the RIO results mean?<\/h2>\n<p><strong>The results showed two main things.<\/strong><\/p>\n<ol>\n<li>bNAbs can work as long-acting HIV drugs that only need to be given every six months.<\/li>\n<li>bNAbs enabled some people to stay off-ART for longer than a year. This involved close viral load monitoring though as part of the study. This was essential to detect early viral load rebound in some people.<\/li>\n<\/ol>\n<h2>How similar was the FRESH study?<\/h2>\n<p><strong>The FRESH study was similar to RIO because it involved stopping ART after giving two bNAbs to people who started ART in early infection.<\/strong><\/p>\n<p>FRESH also reported that some people were able to stay off-ART for more than a year.<\/p>\n<p>The main differences include:<\/p>\n<ul>\n<li>The FRESH study was run in South Africa and enrolled 20 women.<\/li>\n<li>These women had been diagnosed much earlier than the men in RIO. They also started ART earlier.<\/li>\n<li>FRESH was a single group study without a placebo or other control group.<\/li>\n<li>FRESH used two different bNAbs.<\/li>\n<li>Both studies reported that some participants stayed off-ART after the bNAbs had stopped being active against HIV, suggesting a vaccine-like effect.<\/li>\n<\/ul>\n<h2>Future questions<\/h2>\n<p><strong>These were exciting results but there are still lots of questions.<\/strong><\/p>\n<ul>\n<li>How long will the vaccine effect last?<\/li>\n<li>Has the person with the longest response been cured?<\/li>\n<li>What happens if people have a third bNAb infusion?<\/li>\n<li>Can bNAbs be used in different ways.<\/li>\n<li>Why did the bNAbs work for some people and not others?<\/li>\n<li>Is there a way to predict who will respond?<\/li>\n<li>Will bNAbs work for people who were diagnosed later and who started ART later?<\/li>\n<li>Can the bNAbs test become more accurate?<\/li>\n<li>Will newer bNAbs be more effective?<\/li>\n<\/ul>\n<h2>What are bNAbs?<\/h2>\n<p><strong>Some people have very strong immune responses to HIV. They develop antibodies that are so strong that they can control HIV without treatment.<\/strong><\/p>\n<p>These antibodies can disable &#8211; or neutralise &#8211; a broad range of different types of HIV. This is why they are called broadly neutralising antibodies &#8211; or bNAbs for short.<\/p>\n<p>Scientists have also found out how to develop some bNAbs into a new type of HIV treatment.<\/p>\n<p>bNAbs are usually given as an infusion at a research clinic. They are currently being studied as HIV treatment, as prevention like PrEP and in cure-related research (like RIO).<\/p>\n<p>Dozens of different HIV bNAbs have already been developed and many more will be discovered in the future.<\/p>\n<h2>How do bNAbs work?<\/h2>\n<p><strong>RIO showed that bNAbs can work in two different ways.<\/strong><\/p>\n<ol>\n<li>The first way is to directly reduce viral load. This is by working a bit like regular HIV drugs. This was already known.<\/li>\n<li>The second way is that they might also act like a vaccine. The RIO study was the first study to show this vaccine-like effect. This is very exciting.<\/li>\n<\/ol>\n<p><span>There are already dozens of different HIV bNAbs. Some bNAbs are stronger than others. \u00a0<\/span><\/p>\n<p>Many bNAbs are already available in long-acting formulations. So they only need to be taken every 1 to 6 months.<\/p>\n<p>Each bNAb only works for some people. This means taking a test before using them to check they are likely to work. These tests are not yet perfect though, but they are getting better.<\/p>\n<p>Just like antiviral HIV drugs, most studies now use combinations of two or more bNAbs. This reduces the chance of developing resistance.<\/p>\n<p>bNAbs have a very good safety profile.<\/p>\n<p>However, they are currently very expensive to develop and manufacture. If effective though, they should become much less expensive.<\/p>\n<h2>Further information<\/h2>\n<p><strong>It is easy to access reports or to go directly to the presentations at CROI. [1-4]<\/strong><\/p>\n<p>The RIO study website includes more details about the study and videos of interviews with some of the study participants. [7]<\/p>\n<p>More details are included in the listing on clinicaltrials.gov. [8]<\/p>\n<p>References<\/p>\n<ol>\n<li>RIO study: Dual-bNABs keep viral load undetectable off-ART \u2013 plus a potential first case of vaccine-like HIV remission. HTB (21 March 2025).<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/50530\">https:\/\/i-base.info\/htb\/50530<\/a><\/li>\n<li>Fidler S et al for the RIO Trial Investigators. RIO: A Randomised Placebo-Controlled Study of 2 LS-bNAbs in People Treated in Early HIV. CROI 2025. Late-breaking oral abstract 107.<br \/>\n<a href=\"https:\/\/www.croiconference.org\/abstract\/3760-2025\/\">https:\/\/www.croiconference.org\/abstract\/3760-2025\/ (abstract)<\/a><br \/>\n<a href=\"https:\/\/watch.croiwebcasts.org\/2025croi\/ap\/54102\">watch.croiwebcasts.org\/2025croi\/ap\/54102<\/a> (webcast)<\/li>\n<li>Frater J et al for the RIO Trial Investigators. Sustained Post-Rebound HIV Remission With Enhanced T-Cell Immunity After LS-bNAbs: A Case Report. CROI 2025. Poster abstract 505.<br \/>\n<a href=\"https:\/\/www.croiconference.org\/abstract\/2238-2025\/\">https:\/\/www.croiconference.org\/abstract\/2238-2025\/<\/a><\/li>\n<li>Altaf M et al for the RIO Trial Investigators. Sustained T Cell\u2013Mediated Immunity After LS-bNAbs in the RIO Trial: A Vaccinal Effect. CROI 2025. Poster abstract 506.<br \/>\n<a href=\"https:\/\/www.croiconference.org\/abstract\/3809-2025\/\">https:\/\/www.croiconference.org\/abstract\/3809-2025\/<\/a><\/li>\n<li>Two bNAbs enable viral suppression off-ART in African women in the FRESH cohort. HTB (1 April 2025).<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/50674\">https:\/\/i-base.info\/htb\/50674<\/a><\/li>\n<li>Ndung\u2019u T et al for the FRESH study. Evaluation of 2 bNAbs Plus Vesatolimod in Early-Treated South African Women With HIV-1 During ATI. CROI 2025. Oral abstract 105.<br \/>\n<a href=\"https:\/\/www.croiconference.org\/abstract\/2240-2025\">www.croiconference.org\/abstract\/2240-2025<\/a> (abstract)<br \/>\n<a href=\"https:\/\/watch.croiwebcasts.org\/2025croi\/ap\/54100\">watch.croiwebcasts.org\/2025croi\/ap\/54100<\/a> (webcast)<\/li>\n<li>RIO website.<br \/>\nwww.riotrial.org<\/li>\n<li><span>Clinicaltrials.gov. A Randomised Placebo Controlled Trial of ART Plus Dual Long-acting HIV-specific Broadly Neutralising Antibodies (bNAbs). (RIO)<br \/>\n<a href=\"https:\/\/clinicaltrials.gov\/study\/NCT04319367\">clinicaltrials.gov\/study\/NCT04319367<\/a><br \/>\n<\/span><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Simon Collins, HIV i-Base This Q&amp;A is about the RIO study and using immune-based treatments as part of HIV cure-related research. Background In March 2025, the first results from the RIO study were presented at CROI. [1-4] The results showed &hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,20],"tags":[339],"class_list":["post-50971","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-cure-research","tag-croi-2025"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/50971","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=50971"}],"version-history":[{"count":21,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/50971\/revisions"}],"predecessor-version":[{"id":50996,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/50971\/revisions\/50996"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=50971"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=50971"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=50971"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}