Lamivudine-based two-drug regimens with dolutegravir or protease inhibitor: Virological suppression in spite of previous therapy failure or renal dysfunction

Braz J Infect Dis. 2023 May-Jun;27(3):102757. doi: 10.1016/j.bjid.2023.102757. Epub 2023 Feb 19.

Abstract

Background: Two-Drug Regimens (2DR) have proven effective in clinical trials but real-world data, especially in resource-limited settings, is limited.

Objectives: To evaluate viral suppression of lamivudine-based 2DR, with dolutegravir or ritonavir-boosted protease inhibitor (lopinavir/r, atazanavir/r or darunavir/r), among all cases regardless of selection criteria.

Patients and methods: A retrospective study, conducted in an HIV clinic in the metropolitan area of São Paulo, Brazil. Per-protocol failure was defined as viremia above 200 copies/mL at outcome. Intention-To-Treat-Exposed (ITT-E) failure was considered for those who initiated 2DR but subsequently had either (i) Delay over 30 days in Antiretroviral Treatment (ART) dispensation, (ii) ART changed or (iii) Viremia > 200 copies/mL in the last observation using 2DR.

Results: Out of 278 patients initiating 2DR, 99.6% had viremia below 200 copies/mL at last observation, 97.8% below 50 copies/mL. Lamivudine resistance, either documented (M184V) or presumed (viremia > 200 copies/mL over a month using 3TC) was present in 11% of cases that showed lower suppression rates (97%), but with no significant hazard ratio to fail per ITT-E (1.24, p = 0.78). Decreased kidney function, present in 18 cases, showed of 4.69 hazard ratio (p = 0.02) per ITT-E for failure (3/18). As per protocol analysis, three failures occurred, none with renal dysfunction.

Conclusions: The 2DR is feasible, with robust suppression rates, even when 3TC resistance or renal dysfunction is present, and close monitoring of these cases may guarantee long-term suppression.

Keywords: 2DR; 3TC resistance; CKD-EPI; Dual therapy; HIV-1.

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • Anti-Infective Agents* / pharmacology
  • Brazil
  • Drug Therapy, Combination
  • HIV Infections* / drug therapy
  • HIV Protease Inhibitors* / therapeutic use
  • Humans
  • Kidney Diseases* / drug therapy
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use
  • Retrospective Studies
  • Viral Load
  • Viremia / drug therapy

Substances

  • Lamivudine
  • dolutegravir
  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Anti-Infective Agents