Clinical outcomes after the introduction of dolutegravir for second-line antiretroviral therapy in South Africa: a retrospective cohort study

  1. Kwabena Asare
  2. Yukteshwar Sookrajh
  3. Johan van der Molen
  4. Thokozani Khubone
  5. Lara Lewis
  6. Richard J Lessells
  7. Kogieleum Naidoo
  8. Phelelani Sosibo
  9. Rosemary van Heerden
  10. Nigel Garrett
  11. Jienchi Dorward

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Abstract

Background

Dolutegravir is now recommended for second-line anti-retroviral therapy (ART) in low- and middle-income countries. We compared outcomes with dolutegravir (DTG) versus the previous lopinavir/ritonavir (LPV/r) regimen in South Africa.

Methods

We used routinely collected, de-identified data from 59 South African clinics. We included people living with HIV aged ≥ 15 years with virologic failure (two consecutive viral loads ≥1000 copies/mL) on first-line tenofovir disoproxil fumarate (TDF)-based ART and switched to second-line ART. We used modified Poisson regression models to compare outcomes of 12-month retention-in-care and viral suppression (<50 copies/ml) after switching to second-line regimens of zidovudine (AZT), emtricitabine/lamivudine (XTC), DTG and TDF/XTC/DTG and AZT/XTC/LPV/r.

Findings

Of 1214 participants, 729 (60.0%) were female, median age was 36 years (interquartile range 30 to 42), 689 (56.8%) were switched to AZT/XTC/LPV/r, 217 (17.9%) to AZT/XTC/DTG and 308 (25.4%) to TDF/XTC/DTG. Retention-in-care was higher with AZT/XTC/DTG (85.7%, adjusted risk ratio (aRR) 1.14, 95% confidence interval (CI) 1.03 to 1.27; adjusted risk difference (aRD) 10.89%, 95%CI 2.01 to 19.78) but not different with TDF/XTC/DTG (76.9%, aRR 1.01, 95%CI 0.94 to 1.10; aRD 1.04%, 95%CI -5.03 to 7.12) compared to AZT/XTC/LPV/r (75.2%). Retention-in-care with TDF/XTC/DTG was not statistically significantly different from AZT/XTC/DTG (aRR 0.89, 95%CI 0.78 to 1.01; aRD - 9.85%, 95%CI -20.33 to 0.63). Of 799 participants who were retained-in-care with a 12-month viral load, viral suppression was higher with AZT/XTC/DTG (59.3%, aRR 1.25, 95%CI 1.06 to 1.47; aRD 11.57%, 95%CI 2.37 to 20.76) and TDF/XTC/DTG (60.7%, aRR 1.30, 95%CI 1.14 to 1.48; aRD 14.16%, 95%CI 7.14 to 21.18) than with the AZT/XTC/LPV/r regimen (46.7%).

Interpretation

DTG-based second-line regimens were associated with similar or better retention-in-care and better viral suppression than the LPV/r-based regimen. TDF/XTC/DTG had similar viral suppression compared to AZT/XTC/DTG.

Funding

Bill & Melinda Gates Foundation, Africa Oxford Initiative.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Thanyawee Puthanakit, Torsak Bunupuradah

    Review 2: "Clinical Outcomes After the Introduction of Dolutegravir for Second-line Antiretroviral Therapy in South Africa: A Retrospective Cohort Study"

    Reviewers deemed the evidence supporting these claims to be “strong”, with sound methodology ultimately backing up other recent studies and recommendations by the World Health Organization.

  2. Rapid Reviews Infectious Diseases

    Theodore Ruel

    Review 1: "Clinical Outcomes After the Introduction of Dolutegravir for Second-line Antiretroviral Therapy in South Africa: A Retrospective Cohort Study"

    Reviewers deemed the evidence supporting these claims to be “strong”, with sound methodology ultimately backing up other recent studies and recommendations by the World Health Organization.

  4. Version published to 10.1101/2023.07.07.23292347v1 on medRxiv