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This study aims to investigate the prevalence of HIV-1 drug resistance mutations (DRMs) in individuals experiencing immunological failure (IF) while on first-line regimens based on nucleoside reverse transcriptase inhibitors (NRTIs), namely thymidine analogues (TAs) such as AZT and D4T, as well as non-thymidine analogues (NTAs) like TDF. The objective is to assess the viral drug susceptibility in order to inform the selection of optimal second-line therapeutic alternatives.
Cross-sectional study comprised 300 people with HIV-1 infection who were on first-line HAART. The HIV-1 pol gene, which spans 20–240 RT codons, was genotyped using IAS-USA 2014 and the Stanford HIV drug resistance database v7.0.
In total 300 Participant receiving first-line therapy was included. Majority of the TDF failures were on EFV based first-line (89% vs 45%) (p <0.0001), level of resistance for TDF and AZT shows, that resistance to TDF was about one-third (37%) of TDF participants and onefourth (23%) of AZT participants; resistance to AZT was 17% among TDF participants and 47% among AZT participants; resistance to both AZT and TDF was significantly high among AZT participants [21% vs. 8%, OR 3.057 (95% CI 1.4-6.8), p < 0.0001].
Acquired drug resistance were induced by delayed diagnosis of treatment failure. Therefore, we must take steps to regularize virological monitoring with integrated resistance testing in LMIC (Low and Middle Income Countries), such as India; this will help to preserve the effectiveness of ARV and assure the success of eradicating AIDS as a public health concern by 2030.
World Health Organization. Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations. World Health Organization; 2021.
UNAIDS. Fast-Track—Ending the AIDS epidemic by 2030. UNAIDS, 2014.
World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: summary of key features and recommendations, June 2013. World Health Organization; 2013.
Saravanan S, Vidya M, Balakrishanan P, Kumarasamy N, Solomon SS, Solomon S, et al. Evaluation of two human immunodeficiency virus-1 genotyping systems: ViroSeq™ 2.0 and an in-house method. J Virological Methods 2009 ;159: 211-16.
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013; 30: 2725-29.
Rhee SY, Varghese V, Holmes SP, Van Zyl GU, Steegen K, Boyd MA, et al. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: an international collaboration. E Bio Medicine. 2017; 18: 225-35.
Rhee SY, Taylor J, Wadhera G, Ben-Hur A, Brutlag DL, Shafer RW. Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proc Natl Acad Sci U S A. 2006; 103: 17355-60.
Miranda LR, Götte M, Kuritzkes DR. The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. Antimicrob Agents Chemother 2005; 49: 2648-56.
Sunpath H, Wu B, Gordon M, Hampton J, Johnson B, Moosa Y, et al. High rate of K65R for ART naïve patients with subtype C HIV infection failing a TDF-containing first-line regimen in South Africa. AIDS. 2012; 26: 1679.
Hamers RL, Sigaloff KC, Wensing AM, Wallis CL, Kityo C, Siwale M, et al. Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. Clin Infect Dis. 2012; 54: 1660-9.
Manasa J, Lessells RJ, Skingsley A, Naidu KK, Newell ML, McGrath N, et al. Southern African Treatment and Resistance Network (SATuRN). High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa. PloS one. 2013; 8: e72152.
Gregson J, Tang M, Ndembi N, Hamers RL, Rhee SY, Marconi VC, Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Lancet Infect Dis. 2016; 16: 565-75.
Gupta RK, Hill A, Sawyer AW, Cozzi-Lepri A, von Wyl V, Yerly S, et al. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis. Lancet Infect Dis 2009; 9: 409-17.
Moore DM, Awor A, Downing R, Kaplan J, Montaner JS, Hancock J, et al. CD4+ T-cell count monitoring does not accurately identify HIV-infected adults with virologic failure receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2008; 49: 477-84.
Hoffmann CJ, Ledwaba J, Li JF, Johnston V, Hunt G, Fielding KL, et al. Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Antivir Ther. 2013; 18: 915-20.
Dinesha TR, Gomathi S, Boobalan J, Sivamalar S, Solomon SS, Pradeep A, et al. Genotypic HIV-1 drug resistance among patients failing tenofovir-based first-line HAART in South India. AIDS Res Hum Retroviruses. 2016; 32: 1234-6.
Karade S, Chaturbhuj DN, Sen S, Joshi RK, Kulkarni SS, Shankar S, et al. HIV drug resistance following a decade of the free antiretroviral therapy programme in India: A review. Int J Infect Dis. 2018; 66: 33-41.
Kityo C, Thompson J, Nankya I, Hoppe A, Ndashimye E, Warambwa C, et al. HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa. J Acquir Immune Defic Syndr. 2017; 75 : e45-e54.
Skhosana L, Steegen K, Bronze M, Lukhwareni A, Letsoalo E, Papathanasopoulos MA, et al. High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. PloS one. 2015; 10: e0118145.
Miller MD, Margot N, Lu B, Zhong L, Chen SS, Cheng A, et al. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. J Infect Dis. 2004; 189: 837-46.
Van Zyl GU, Liu TF, Claassen M, Engelbrecht S, De Oliveira T, Preiser W, et al. Trends in genotypic HIV-1 antiretroviral resistance between 2006 and 2012 in South African patients receiving first-and second-line antiretroviral treatment regimens. PloS one. 2013; 8: e67188.
De Luca A, Dunn D, Zazzi M, Camacho R, Torti C, Fanti I, et al. Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe. The J Infect Dis. 2013; 207: 1216-20.
Wallis CL, Mellors JW, Venter WD, Sanne I, Stevens W. Varied patterns of HIV-1 drug resistance on failing first-line antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr. 2010; 53: 480-4.
Sigaloff KC, Hamers RL, Wallis CL, Kityo C, Siwale M, Ive P, et al. Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa. J Acquir Immune Defic Syndr. 2011; 58: 23-31.
Gupta RK, Hill A, Sawyer AW, Cozzi-Lepri A, von Wyl V, Yerly S, et al. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis. Lancet Infect Dis. 2009; 9: 409-17.
Bunupuradah T, Ananworanich J, Chetchotisakd P, Kantipong P, Jirajariyavej S, Sirivichayakul S, et al. Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens. Antivir Ther. 2011; 16: 1113-21.
Bannister WP, Ruiz L, Cozzi-Lepri A, Mocroft A, Kirk O, Staszewski S, et al. Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA. Aids. 2008; 22: 367-76.
Katlama, Christine, Bonaventura Clotet, Anthony Mills, Benoit Trottier, Jean-Michel Molina, et al. Short communication Efficacy and safety of etravirine at week 96 in treatment-experienced HIV type-1-infected patients in the DUET-1 and DUET-2 trials. Antivir Ther. 2010; 15: 1045–1052.
Madruga JV, Cahn P, Grinsztejn B, Haubrich R, Lalezari J, Mills A, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007; 370: 29-38.
Poveda E, de Mendoza C, Pattery T, del Mar González M, Villacian J, Soriano V. Phenotypic impact of resistance mutations on etravirine susceptibility in HIV patients with prior failure to nonnucleoside analogues. Aids. 2008; 22: 2395-8.