Viral suppression with antiretroviral therapy after single drug substitution of efavirenz with dolutegravir at an HIV Centre in Karachi, Pakistan

Authors

  • Saima Samad Shaheed Mohtarma Benazir Bhutto Institute of Trauma, Karachi Pakistan
  • Nazish Misbah Shaheed Mohtarma Benazir Bhutto Institute of Trauma, Karachi Pakistan
  • Sughand Memon Mir Shaheed Mohtarma Benazir Bhutto Institute of Trauma, Karachi Pakistan
  • Sadia Ishaque Shaheed Mohtarma Benazir Bhutto Institute of Trauma, Karachi Pakistan
  • Obaidullah Farooqui Pakistan Air Force Karachi Institute of Economics and Technology, Karachi Pakistan
  • Shehla Baqi Bronxcare Health System, New York, United States of America

DOI:

https://doi.org/10.61529/idjp.v33i1.277

Abstract

Background: AIDS was first reported in the 1980s. The HIV prevalence rate among Pakistani adults is 0.2%.  The Sindh Center for AIDS Control Programs (SACP) was established in Karachi in 2006. In 2018, the SACP introduced the integrase chain transfer inhibitor dolutegravir (DTG) and lamivudine (3TC) and tenofovir diproxilfumarate (TDF). Patients who developed virological failure on Efavirenz, 3TC, and TDF were switched to DTG/3TC/TDF. As the two nucleoside reverse transcriptase inhibitors remained the same, EFV and DTG were effectively substituted as single agents. We assessed immunological, virological and clinical responses to DTG.

Material and Methods: A retrospective chart review was conducted at the SACP of adults with virological failure on EFV/3TC/TDF who were switched to DTG/3TC/TDF from April 2019 till November 2023.

Results: The 14 patients were switched after a mean of 28.2 months of prior antiretroviral therapy with mean CD4 of 116 cells/mm3. Mean age was 28.4 years with 7 (50.0%) males.12 were adherent to the DTG regimen; 11 (92 %) achieved viral suppression. The Mean period of suppression was31 months. There was no clinical or immunological failure with upsurge of mean CD4 to 632 cells/mm3.

Conclusion: The patients with virological failure on an efavirenz-based regimen are likely to have viral suppression after switch to a dolutegravir-based routine even if they potentially have NRTI resistance. These results are relevant to HIV programs in resource-poor settings where switches between regimens are often implemented without frequent viral load or resistance testing. 

Keywords: HIV, Dolutegravir, Efavirenz, Tenofovir, Viral suppression, CD4 count

References

www.unaids.org/en/regionscountries/countries/pakistan

https://www.cmu.gov.pk/nacp-national-aids-control-prog ramme/nacp-national-aids-control-programmed-treatmzet/

Pakistan Country Snapshot 2023 | HIV/AIDS Data Hub for theAsia-PacificRegionpak-snapshot-2023.pdf (aidsdatahub.org)

https://www.unaids.org/sites/default/files/country/documents/PAK_2020_countryreport.pdf

Mir F, Nathwani AA, Simms V, Abidi SH, Siddiqui AR, Hotwani A, et al. Factors associated with HIV infection among children in Larkana District, Pakistan: A matched case-control study. Lancet HIV. 2021; 8(6): e342-e52. DOI: https://doi.org/10.1016/S2352-3018(21)00049-7

Baqi S, Abro AG, Salahuddin N, Memon MA, Qamar Abbas S, Baig-Ansari N. Four years of experience with antiretroviral therapy in adult patients in Karachi, Sindh, Pakistan. Int Health. 2012; 4(4): 260-7. DOI: https://doi.org/10.1016/j.inhe.2012.07.002

Batool FMS, Dhiloo AU, Ismail HM, Shaikh SM, Baqi S. Experience with dolutegravir in HIV patients at a public sector hospital in Karachi, Pakistan. Pak Armed Forces Med J. 2021;2021; 71(5): 1661-5. DOI: https://doi.org/10.51253/pafmj.v71i5.6288

McCluskey SM, Siedner MJ, Marconi VC. Management of virologic failure and HIV drug resistance. Infect Dis Clin North Am. 2019; 33(3): 707-42. DOI: https://doi.org/10.1016/j.idc.2019.05.004

World Health Organization. HIV Drug Resistance Report. Geneva: World Health Organization; 2017

World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. 2nd ed. Geneva: World Health Organization; 2016

Update of recommendations on first- and second-line antiretroviral regimens. Geneva: World Health Organization, July 2019 (https://apps.who.int/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-eng.pdf?ua=1.

Kandel CE, Walmsley SL. Dolutegravir - a review of the pharmacology, efficacy, and safety in the treatment of HIV. Drug Des Devel Ther. 2015; 9: 3547-55. DOI: https://doi.org/10.2147/DDDT.S84850

Rusconi S, Adorni F, Tau P, Borghi V, Pecorari M, Maserati R, et al. Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA). J Clin Virol. 2018; 105: 112-7. DOI: https://doi.org/10.1016/j.jcv.2018.06.012

Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, et al. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. Lancet HIV. 2022; 9(6): e381-93. DOI: https://doi.org/10.1016/S2352-3018(22)00092-3

Keene CM, Griesel R, Zhao Y, Gcwabe Z, Sayed K, Hill A, et al. Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen. AIDS. 2021; 35(9): 1423-32. DOI: https://doi.org/10.1097/QAD.0000000000002936

Ross L, Parkin N, Lanier R. Short communication: The number of HIV major NRTI mutations correlates directly with other antiretroviral-associated mutations and indirectly with replicative capacity and reduced drug susceptibility. AIDS Res Human Retroviruses. 2008; 24(4): 617-20. DOI: https://doi.org/10.1089/aid.2007.0188

Rolle CP, Berhe M, Singh T, Ortiz R, Wurapa A, Ramgopal M, et al. Sustained virologic suppression with dolutegravir/ lamivudine in a test-and-treat setting through 48 weeks. Open Forum Infect Dis. 2023; 10(3): ofad101. DOI: https://doi.org/10.1093/ofid/ofad101

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; 15(6): e40139. DOI: https://doi.org/10.7759/cureus.40139

Ayal MA, Berha AB. Comparative safety and changes in immunologic and virologic parameters of dolutegravir versus efavirenz-based antiretroviral therapies among HIV Patients: A retrospective cohort study. HIV AIDS (Auckl). 2023; 15: 173-90. DOI: https://doi.org/10.2147/HIV.S396420

Calmy A, Tovar Sanchez T, Kouanfack C, Mpoudi-Etame M, Leroy S, Perrineau S, et al. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicenter, randomized, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV. 2020;7(10): e677-e87. DOI: https://doi.org/10.1016/S2352-3018(20)30238-1

Brennan AT, Nattey C, Kileel EM, Rosen S, Maskew M, Stokes AC, et al. Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir adults living with HIV: Evidence from routine care in Johannesburg, South Africa. EClinicalMedicine. 2023; 57: 101836. DOI: https://doi.org/10.1016/j.eclinm.2023.101836

Downloads

Published

2024-03-29