Fundamentals of Cellular and Molecular Biology

Molecular Mechanisms of Human Immunodeficiency Virus Resistance to Antiretroviral

Author(s): Saima Pervaiz* and Shehryar Awan

Pp: 225-241 (17)

DOI: 10.2174/9789815238037124010020

* (Excluding Mailing and Handling)

Abstract

Antiretroviral therapy (ART) has transformed the treatment of human immunodeficiency virus (HIV) infection, improving life expectancy and quality of life for millions worldwide. However, the emergence of drug-resistant HIV strains poses a significant challenge to the effectiveness of ART. The molecular mechanisms underlying HIV resistance to antiretroviral drugs involve multiple genetic changes in the viral genome that reduce drug susceptibility, often through alterations in the viral enzymes targeted by the drugs. The primary targets of ART are the viral reverse transcriptase (RT), protease (PR), and integrase (IN) enzymes, which are essential for HIV replication. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) results from mutations in the viral RT enzyme that reduce drug incorporation into the viral DNA chain. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to a hydrophobic pocket near the RT active site, and resistance to these drugs arises from mutations that alter the binding pocket conformation. Protease inhibitors (PIs) bind to the viral PR enzyme, and resistance results from mutations that alter the enzyme's conformation, reducing drug binding affinity. Integrase strand transfer inhibitors (INSTIs) bind to the viral IN enzyme, and resistance arises from mutations that affect drug binding or alter the IN active site. The emergence of drug-resistant HIV strains can also result from poor adherence to ART, leading to the selection of pre-existing resistant viruses or the development of new resistance mutations. In addition, the genetic diversity of HIV and the high viral replication and mutation rate contribute to the rapid evolution and emergence of drug-resistant strains.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873346344 and j.to_ip >=873346344 )) and ((j.from_date <= 1740516105 and j.to_date >= 1740516105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 22298) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873346344 and j.to_ip >=873346344 )) and ((j.from_date <= 1740516105 and j.to_date >= 1740516105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 22298) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873346344 and j.to_ip >=873346344 )) and ((j.from_date <= 1740516105 and j.to_date >= 1740516105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 22298)
      750μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3705 and `b`.`banner_from_date` <= 1740516105 and `b`.`banner_to_date` >= 1740516105 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3705
      • 3: 1740516105
      • 4: 1740516105
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='e41d8284c37fab12e73ca20f9a3b50f5'
      210μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        7CiZIMWXbQHTUZTRp05B20z49KrJQ7L3Jb3qhwdv
        uc_cart_id
        e41d8284c37fab12e73ca20f9a3b50f5
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/22298" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/22298
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImRjTm5hc3BZcWhwUTV4TnN4UWRGN1E9PSIsInZhbHVlIjoiS0ppL29jTnk3Z3VSazc5eEdySHBGclIvQ3pPTzdoSGlOMDA2ZGZ5ckNDOD0iLCJtYWMiOiI2MDQ2NjdjOTIyMjhmYzZhZmMyOTg4YTk4MTVkMDExODE4YTVmZTRkOTIxNjE1ZGEwZGU1YWFmMTk4NDUwYzljIiwidGFnIjoiIn0%3D; XSRF-TOKEN=eyJpdiI6ImRIL0RpS3lTMkNGSGo3eHNQeDByY1E9PSIsInZhbHVlIjoiczIwOWhIU3MzZlh3SXpLcUZFQTNoVDArdVhKN2ZJNVJEM3cwUzErdWl0cnhaYkg0SENRdWVvdllvSzhyc1RRRUlId2RORXVtZ2xoeFRwclZqNXdpZWpZWHRLL050TWNqZk5kN055em5vSVFkT1oyRnFtSndhQUswVUFEcVdmQXgiLCJtYWMiOiJiNDhhMzVkZDJlNGM5NzA3NDAyNDVjNjlmY2Y2YzMyMTQ2MGExZTY0OTQ4Mzg1OTBhM2I5MzdjMTg5MmNlY2Y2IiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6IjZwSHhFY1EzNjdidDMwQmhNVERCMGc9PSIsInZhbHVlIjoiUFNEVXNoRTNLSFVrbmptZk1iRTR2MHdtMkJhSVd5M2VGT0sxQ0owU1ZIWFZSaWQ4cDRTQ0g4YkpYL1FLZWxOSXorMGdJeEZ6Z2toZ2pvaTcvMUFmVEtQandPdkhOZFM0SU9IVlJBVldDNDFuNU1OSkUrN1hZSWowa3hPbXV5OUsiLCJtYWMiOiJkMjE0MWE3YTUxZjk1N2JiNTMwY2QwNDAyYmU3NTU3YjdhNWYxNWZlYmZlYjYzMmYzNzJhMjg4ODg3YzhhNTM5IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImRjTm5hc3BZcWhwUTV4TnN4UWRGN1E9PSIsInZhbHVlIjoiS0ppL29jTnk3Z3VSazc5eEdySHBGclIvQ3pPTzdoSGlOMDA2ZGZ5ckNDOD0iLCJtYWMiOiI2MDQ2NjdjOTIyMjhm" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        session_attributes
        0 of 0
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:41:45GET/chapter/22298112192