The clinical efficacy of integrating dolutegravir into the conventional therapeutic regimen for HIV management
Abstract
This study investigates the efficacy of transitioning from TLE (Tenofovir/Lamivudine/Efavirenz) to TLD (Tenofovir/ Lamivudine/ Dolutegravir) as a first-line antiretroviral therapy for the management of HIV. A retrospective analysis was conducted involving 261 individuals in whom 145 patients were initially treated with TLE in 2017 who were transitioned to TLD in 2020 and 116 patients given TLD as first-line therapy from 2020 onwards. Clinical parameters like Viral load (VL), CD4 cell count, and WHO clinical stage were evaluated at baseline to study the effectiveness of the treatment. In addition, the non-clinical variables like age, sex, weight, mode of transmission and body mass index (BMI) were analyzed. The results signified enhancements in CD4 count, viral load and weight across both groups (TLE to TLD transition and TLD initiated as first-line therapy) with a statistical significance of P<0.001***. The median BMI for patients transitioning from TLE to TLD was 21.63 (IQR 19.62-24.37) with a p-value of 0.004**, while the median BMI for patients on TLD as a first-line therapy was 20.83 (IQR 18.95-23.87), exhibiting a p-value of 0.115ns indicating no substantial difference between both groups. The findings showed effective viral suppression, with viral loads categorized as Target Not Detected (TND) and CD4 counts exceeding 500 cells/mm3. Overall, the integration of TLD into ART regimen resulted in improved clinical outcomes and sustained viral suppression among the patients showing the advantage of this therapeutic transition in HIV management.
Keywords:
Dolutegravir, Viral Load, CD4, HIV, TNDDOI
https://doi.org/10.25004/IJPSDR.2024.160603References
Deeks SG, Overbaugh J, Phillips A, Buchbinder S. HIV infection. Nature reviews Disease primers. 2015 Oct 1;1(1):1-22. Available From: https://doi.org/10.1038/nrdp.2015.35
Assembly UG. Political declaration on HIV and AIDS: ending inequalities and getting on track to end AIDS by 2030. In74th Plenary Meeting 2021 Jun 8 (Vol. 8):5-10. Available From: https://www.unaids.org/sites/default/files/media_asset/2021_political-declaration-on-hiv-and-aids_en.pdf
Ray I, Hasan MM, Shah PA, Sahito AM, Sarkar A, Ghosh D, et al. HIV epidemic amidst COVID-19 pandemic in India: a conundrum for the country’s healthcare system. Epidemiology and Infection. 2022;150:e112. Available From: 10.1017/S095026882200098X
Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, Sax PE, Smith DM, Thompson MA, Buchbinder SP, Del Rio C. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society–USA Panel. Jama. 2018 Jul 24;320(4):379-96. Available From: 10.1001/jama.2018.8431
Foka FE, Mufhandu HT. Current ARTs, virologic failure, and implications for AIDS management: a systematic review. Viruses. 2023 Aug 13;15(8):1732. Available From: 10.3390/v15081732
World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines: supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. World Health Organization; 2018 pp.16
Ribera E, Podzamczer D, Mecanismo de acción, farmacología e interacciones de . (2015) dolutegravir. Enfermedadesinfecciosas y microbiologiaclinica. Mar 1;33:2-8. Available From: https://doi.org/10.1016/S0213-005X(15)30002-1
Twimukye A, Laker M, Odongpiny EA, Ajok F, Onen H, Kalule I, Kajubi P, Seden K, Owarwo N, Kiragga A, Armstrong-Hough M.(2021) Patient experiences of switching from Efavirenz-to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda. BMC Infectious Diseases. Dec;21:1-4. Available From: 10.1186/s12879-021-06851-9
World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization; 2016. Available From:[PubMed] PMID: 27466667
Mahale PR, Patel BS, Kasmani N. Treatment outcomes of dolutegravir-versus efavirenz-based highly active antiretroviral therapy regimens among treatment-naive people living with HIV. Cureus. 2023 Jun;15(6). Available From: 10.7759/cureus.40139
Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, Sax PE, Smith DM, Thompson MA, Buchbinder SP, Del Rio C. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society–USA Panel. Jama. 2018 Jul 24;320(4):379-96. Available From: https://doi.org/10.1001/jama.2018.8431
World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. World Health Organization; 2021 Jul 16 pp.23
Patel AK, Patel KK, Pujari S, Patel JK, Kumar A. Virological outcome and frequency of low-level viremia in patients receiving generic dolutegravir-containing regimen at a large tertiary care clinic in Western India. Indian Journal of Sexually Transmitted Diseases and AIDS. 2021 Jan 1;42(1):31-7. Available From: 10.4103/ijstd.IJSTD_34_20
Weinberg JL, Kovarik CL. The WHO clinical staging system for HIV/AIDS. AMA Journal of Ethics. 2010 Mar 1;12(3):202-6. Available From: 10.1001/virtualmentor.2010.12.3.cprl1-1003
Kandel CE, Walmsley SL. Dolutegravir–a review of the pharmacology, efficacy, and safety in the treatment of HIV. Drug design, development and therapy. 2015 Jul 7:3547-55.Available From: 10.2147/DDDT.S84850
Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. Aids. 2001 Jan 5;15(1):71-5. Available From: 10.1097/00002030-200101050-00011
Suárez‐García I, Alejos B, Ruiz‐Algueró M, Yubero CG, Moreno C, Bernal E, Pérez‐Is L, Zubero Z, de Zárraga Fernández MA, Abad GS, Jarrín I. Effectiveness and tolerability of dolutegravir and abacavir/lamivudine administered as two separate pills compared to their equivalent single‐tablet regimen in a multicentre cohort in Spain. African Journal of Reproduction and Gynaecological Endoscopy. 2021 Jul 1;24(7):e25758. Available From: 10.1002/jia2.25758
Govender S, Otwombe K, Essien T, Panchia R, De Bruyn G, Mohapi L, Gray G, Martinson N. CD4 counts and viral loads of newly diagnosed HIV-infected individuals: implications for treatment as prevention. PloS one. 2014 Mar 4;9(3):e90754. Available From: 10.1371/journal.pone.0090754
Phillips AN, Staszewski S, Weber R, Kirk O, Francioli P, Miller V, Vernazza P, Lundgren JD, Ledergerber B. (2001) Swiss HIV Cohort Study. HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. Jama. Nov 28;286(20):2560-7. Available From:10.1001/jama.286.20.2560
Preston SH, Fishman E, Stokes A. Effects of categorization and self-report bias on estimates of the association between obesity and mortality. Annals of Epidemiology. 2015 Dec 1;25(12):907-11. Available From: 10.1016/j.annepidem.2015.07.012
Malamba SS, Morgan D, Clayton T, Mayanja B, Okongo M, Whitworth J. The prognostic value of the World Health Organisation staging system for HIV infection and disease in rural Uganda. Aids. 1999 Dec 24;13(18):2555-62. Available From: 10.1097/00002030-199912240-00009
Weinberg JL, Kovarik CL. The WHO clinical staging system for HIV/AIDS. AMA Journal of Ethics. 2010 Mar 1;12(3):202-6. Avialable From: 10.1001/virtualmentor.2010.12.3.cprl1-1003
World Health Organization. Interim WHO clinical staging of HVI/AIDS and HIV/AIDS case definitions for surveillance: African Region. World Health Organization; 2005. Pp.19-28
McDonagh EM, Lau JL, Alvarellos ML, Altman RB, Klein TE. PharmGKB summary: Efavirenz pathway, pharmacokinetics. Pharmacogenetics and genomics. 2015 Jul 1;25(7):363-76.. Available From: 10.1097/FPC.0000000000000145
Maartens G, Sinxadi P, Venter WD. Weight gain on dolutegravir: Association is not the same as causation. Southern African Journal of HIV Medicine. 2023;24(1):1-2. Available From: 10.4102/sajhivmed.v24i1.1500
Zheng A, Kumarasamy N, Huang M, Paltiel AD, Mayer KH, Rewari BB, Walensky RP, Freedberg KA. The cost‐effectiveness and budgetary impact of a dolutegravir‐based regimen as first‐line treatment of HIV infection in India. African Journal of Reproduction and Gynaecological Endoscopy. 2018 Mar 1;21(3). Available From: 10.1002/jia2.25085
Echefu SN, Udosen JE, Akwiwu EC, Akpotuzor JO, Obeagu EI. Effect of Dolutegravir regimen against other regimens on some hematological parameters, CD4 count and viral load of people living with HIV infection in South Eastern Nigeria. Medicine. 2023 Nov 24;102(47):e35910. Available From: 10.1097/MD.0000000000035910
Di Santo R. Inhibiting the HIV integration process: past, present, and the future. Journal of medicinal chemistry. 2014 Feb 13;57(3):539-66. Available From: 10.1021/jm400674a
Tamrakar R, Tamrakar D. (2022) Virologic Response Following a Switch to Dolutegravir-based Regimen in People Living with HIV/AIDS at a Tertiary Care Center in Nepal. Kathmandu University Medical Journal. Dec 31;20(4):438-42. Pp.441
Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, Brown TT, Rockstroh JK, Wei X, Carter CC, Zhong L. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clinical Infectious Diseases. 2020 Sep 15;71(6):1379-89. Available From: https://doi.org/10.1093/cid/ciz999
Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here?. Science. 2003 Feb 7;299(5608):853-5. Available From: 10.1126/science.1079857
Griesel R, Kawuma AN, Wasmann R, Sokhela S, Akpomiemie G, Venter WF, Wiesner L, Denti P, Sinxadi P, Maartens G. Concentration–response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy. British journal of clinical pharmacology. 2022 Mar;88(3):883-93. Available From: https://doi.org/10.1111/bcp.15177
Esber AL, Chang D, Iroezindu M, Bahemana E, Kibuuka H, Owuoth J, Singoei V, Maswai J, Dear NF, Crowell TA, Polyak CS. Weight gain during the dolutegravir transition in the African Cohort Study. Journal of the International AIDS Society. 2022 Apr;25(4):e25899. Available From: https://doi.org/10.1002/jia2.25899
Semengue EN, Fokam J, Etame NK, Molimbou E, Chenwi CA, Takou D, Mossiang L, Meledie AP, Yagai B, Nka AD, Dambaya B. Dolutegravir-based regimen ensures high virological success despite prior exposure to efavirenz-based first-line ART in Cameroon: an evidence of a successful transition model. Viruses. 2022 Dec 21;15(1):18. Available From: https://doi.org/10.3390/v15010018
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