Still, during clinical trials<\/a> and in in-vitro studies<\/a>, clinicians and researchers noted the emergence of resistance to the drug. \u201cAcross all of those [trials], resistance has been a rare outcome,\u201d says Jared Baeten, senior vice president of clinical development and virology head at Gilead Sciences. Now, in a recent study, Gilead scientists and coauthors found that when resistance occurs, it frequently results in a less fit virus with substantial replication defects<\/a> (Sci. Transl. Med. 2026, DOI: 10.1126\/scitranslmed.aea0947).<\/p>\n While that\u2019s reassuring, \u201cThe most important thing for an individual patient living with HIV is to keep their viral levels undetectable,\u201d Baeten says. But the findings of the study can help scientists develop the next generation of drugs with improved resistance profiles \u201cbecause we always want to stay ahead of the virus,\u201d he adds.<\/p>\n The research team notes that the main risk for developing resistance was nonadherence to antiretrovirals that patients needed to take daily alongside lenacapavir for HIV treatment. In the journal paper, the researchers characterized resistance-associated mutations in the virus\u2019s capsid protein and found that the M66I mutation, for instance, reduced the virus\u2019s replication capacity to 17% in one trial participant. But over time, accumulation of additional mutations, N74D and A105T, restored viral fitness to 34%.<\/p>\n In a commentary accompanying the study<\/a>, virologists Manish Chandra Choudhary and Jonathan Li at Harvard Medical School, who weren\u2019t involved in the research, note that lenacapavir resistance \u201cis not static but a moving target.\u201d They also highlight the importance of using companion active antiretrovirals consistently during HIV treatment and the need for resistance surveillance and testing.<\/p>\n Gilead\u2019s researchers are currently working on developing longer-acting drugs that can be used in combination with lenacapavir. Their hope is to overcome the adherence challenge posed by antiretrovirals that need to be taken daily.<\/p>\n![\"Structure](\"https:\/\/www.europesays.com\/ie\/wp-content\/uploads\/2026\/01\/HIV-can-evolve-to-develop-resistance-to-Lenacapavir--but-often-there-s-a-penalty---325742.jpg\")
\n Structure of lenacapavir.<\/p>\n
![\"Priyanka](\"https:\/\/www.europesays.com\/ie\/wp-content\/uploads\/2026\/01\/2025-priyankacc.jpg\")
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