Clinical Outcomes of 2-Drug Regimens vs 3-Drug Regimens in Antiretroviral Treatment–Experienced People Living With Human Immunodeficiency Virus

Abstract

Background Limited data exist comparing clinical outcomes of two-drug regimens (2DRs) and three-drug regimens (3DRs) in people living with HIV. Methods Antiretroviral treatment-experienced individuals in RESPOND switching to a new 2DR or 3DR from 1/1/12-1/10/18 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. Results Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median 52.6 years [interquartile range 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27,159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU [95% CI 20.7-24.5]) on 3DRs, 79 (30.9/1000 PYFU [24.8-38.5]) on 2DRs. The most common events were death (7.5/1000 PYFU [95% CI 6.5-8.6]) and non-AIDS cancer (5.8/1000 PYFU [4.9-6.8]). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio: 0.92 [0.72-1.19]; p=0.53). Conclusions This is the first large, international cohort assessing clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes; further research on resistance barriers and long-term durability of 2DRs is needed.

Changes in Inflammatory and Atherogenesis Biomarkers With the 2-Drug Regimen Dolutegravir Plus Lamivudine in Antiretroviral Therapy–Experienced, Virologically Suppressed People With HIV-1: A Systematic Literature Review

“…The minimal biomarker changes observed are as expected, given similar outcomes in viral replication demonstrated in clinical trials that showed no significant difference in rates of virologic suppression, residual viremia, and viral blips with dolutegravir/lamivudine 2DR vs comparator 3/4DRs [ 17–20 , 22 ]. The clinical significance of these small fluctuations in inflammatory biomarkers is unknown and data have not demonstrated a difference in AIDS-related or non-AIDS-related clinical endpoints between 3/4DRs and 2DRs [ 39 , 40 ]. Changes in CD4 + /CD8 + ratio were similar between dolutegravir/lamivudine vs comparator postswitch in randomized controlled trials.…”

Characteristics of 2-drug regimen users living with HIV-1 in a real-world setting: A large-scale medical claim database analysis in Japan

“…They also found that individuals initiating 2-ART were older and had shorter time-to-discontinuation [ 30 ]. These differences, especially older age and more comorbidities, are also well established in recent real world comparisons [ 31 – 33 ]. The significantly higher proportion of renal disease, hemodialysis and bone disorders in the 2-ART cohort compared with 3-ART cohort might be a reason for the choice of NRTI-sparing regimen.…”

A Step Closer to the “Fourth 90”: A Practical Narrative Review of Diagnosis and Management of Nutritional Issues of People Living with HIV

“…The role of cART in dyslipidemia is still not fully clear but could be partially explained by alteration of triglycerides hepatic synthesis and alterations of retinoic acid and LDLbinding proteins [45,46]. In any case, recently developed antiretroviral drugs, such as raltegravir, dolutegravir, bictegravir, rilpivirine and doravirine have a safer impact on lipid profile compared to older ones (such as zidovudine, stavudine, nevirapine, and partially lamivudine); two-drug combination regimens are also a modern therapeutic option that could permit, importantly, in selected PLWH, decrease of the pharmacological burden without losing efficacy in virological suppression [47,48].…”