{"id":49872,"date":"2025-01-01T12:00:45","date_gmt":"2025-01-01T12:00:45","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=49872"},"modified":"2025-01-15T21:07:35","modified_gmt":"2025-01-15T21:07:35","slug":"49872","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/49872","title":{"rendered":"Transient impact of lenacapavir against MDR HIV-2 without other active ART"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

The rapid development of drug resistance to lenacapavir when used as the only active drug as part of rescue therapy against multidrug resistant HIV-2 was reported in a brief case review in CID.<\/strong><\/p>\n

Thomas Montrouge and colleagues reported on eight people enrolled in the French ANRS-MIE CO5 HIV-2 cohort who had received lenacapavir on named patient access.<\/p>\n

Participant characteristics included 4 men and 4 women with a median age 57 (range: 36 to 66) years. All 8\/8 had extensive drug resistance and were already on an individualised optimised background regimen (OBR).<\/p>\n

The median genotypic susceptibility score (GSS) to the OBR was 1.25 (range: 0 to 2.5), with 5\/8 having \u22641 fully active drug; 3\/8 used ibalizumab, 2\/8 maraviroc, 1\/8 foscarnet.<\/p>\n

Viral load at day 0 was detectable in 6\/8 (median: 3,830 c\/mL, range: 665 to 60,450) and became undetectable within 3 months in 4\/6 after adding lenacapavir with 2\/8 reaching <200 c\/mL at month 6.<\/p>\n

Although median viral load at month 6 was 757 c\/mL (range: 117 to 3,000), by month 12 viral rebound to baseline levels was reported in all participants (to approximately 500 to >10,000 c\/mL).<\/p>\n

Median trough concentrations at month 6 after the first injection (IQR: 157 to 182 days) was 89 ng\/mL (IQR: 27 to 181). Although in-vitro efficacy has been reported for lenacapavir against HIV-2, with an EC50 that is a log higher than against HIV-1, at 1 nM vs 0.1 nM, respectively, both concentrations remain significantly below the lenacapavir trough levels reported.<\/p>\n

Lenacapavir drug resistance was reported in the 5\/8 participants with the highest drug concentrations. For details on resistance mutations please see the full paper.<\/p>\n

CD4 responses were highly heterogeneous from 135 cells\/mm3<\/sup> (range: 0 to 360) at baseline to 185 cells\/mm3<\/sup> (range: 90 to 290) at month 6, with a median change of +3 cells\/mm3<\/sup> but a range of \u2013110 to +130.<\/p>\n

Importantly, the authors emphasised that the low immunological and virological responses in this study “should not preclude the use of lenacapavir in other populations with MDR HIV-2, especially if they have a higher GSS >2.0”.<\/p>\n

comment<\/h3>\n

These results are disappointing and they show the vulnerability of lenacapavir against HIV-2 if not supported by other active HIV drugs. Even when trough levels suggested continued drug sensitivity, achieving undetectable viral load <50 c\/mL was only transient.<\/strong><\/p>\n

Although not discussed in the paper, the limitations of predicting genotypic sensitivity also needs to be considered as lenacapavir responses did not closely correlate with the GSS.<\/strong><\/p>\n

Although the potency of lenacapavir might be supported in this setting by using a shorter experimental 4-monthly dosing schedule, 6\/8 viral failures were reported earlier in the dosing cycle.<\/strong><\/p>\n

Reference<\/p>\n

Montrouge T et al. Rapid selection of HIV-2 capsid mutations in salvage therapy with lenacapavir-containing regimen. Clinical Infectious Diseases, 2024; ciae650. (31 December 2024).
\ndoi.org\/10.1093\/cid\/ciae650<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base The rapid development of drug resistance to lenacapavir when used as the only active drug as part of rescue therapy against multidrug resistant HIV-2 was reported in a brief case review in CID. Thomas Montrouge and …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,41,43,36],"tags":[],"class_list":["post-49872","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals","category-treatment-strategies","category-virology","category-drug-resistance"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/49872","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=49872"}],"version-history":[{"count":25,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/49872\/revisions"}],"predecessor-version":[{"id":50054,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/49872\/revisions\/50054"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=49872"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=49872"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=49872"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}