Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

Abstract

Background: Two-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.

Methods: Virologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA^® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.

Results: A total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).

Conclusions: Among virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Keywords: 2-drug regimen; 3-drug regimen; Antiretroviral therapy; Bictegravir/emtricitabine/tenofovir alafenamide; Cohort; Dolutegravir; Dolutegravir/lamivudine; Effectiveness; HIV.

Fig. 1

Incidence rates of confirmed virologic failure and association between ART regimen and confirmed virologic failure, by ART regimen (DTG/3TC, BIC/FTC/TAF, DTG 3DR) 3DR, 3-drug regimen; 3TC, lamivudine; ART, antiretroviral therapy; BIC, bictegravir; CI, confidence interval; DTG, dolutegravir; FTC, emtricitabine; HR, hazard ratio; IR, incidence rate; py, person-years; TAF, tenofovir alafenamide. ^a Marginal structural Cox proportional hazards models with stabilized inverse probability of treatment weights controlling for baseline age (linear & quadratic), number of ART classes (linear & quadratic), female, Black race, Hispanic ethnicity, Southern US, core agent class of prior regimen, CD4 cell count (linear & quadratic)

Fig. 2

Reasons for ART regimen discontinuation identified from healthcare provider notes, lab results, and diagnoses, by ART regimen (DTG/3TC, BIC/FTC/TAF, DTG 3DR). 3DR, 3-drug regimen; 3TC, lamivudine; ART, antiretroviral therapy; BIC, bictegravir; DTG, dolutegravir; Dx, diagnosis; FTC, emtricitabine; mL, milliliter; TAF, tenofovir alafenamide; VL, viral load. ^a Last VL > 200 copies/mL, adverse diagnosis/side effect (i.e., new mental health, liver, renal or bone comorbidity diagnosed within 21 days before discontinuation, or as noted), lab abnormality (i.e., alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST] or bilirubin > 3 times the upper limits of normal within 21 days of discontinuation). ^b Simplification; access issues; non-adherence; treatment gap; patient/provider choice; any other reason noted