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 that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus.

Methods: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 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%) started 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% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 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; 95% CI: 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; 95% CI: .72-1.19; P = .53).

Conclusions: This is the first large, international cohort to assess 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.

Keywords: 2-drug regimens; HIV; antiretroviral treatment; clinical outcomes; dual therapy.

Figure 1.

Study flow chart. *More than 1 reason can apply. ^†3DRs consisted of 2 nucleoside reverse transcriptase inhibitors plus the third drug listed. 3DRs were chosen so that the third drug included the same ARVs listed in the 2DRs. Abbreviations: 2DR, 2-drug regimen; 3DR, 3-drug regimen; 3TC, lamivudine; ART, antiretroviral therapy; ARV, antiretroviral; ATV, atazanavir; ATV/b, boosted ATV; DRV/b, boosted darunavir; DTG, dolutegravir; ETV, etravirine; INSTI, integrase inhibitor; NVP, nevirapine; RAL, raltegravir; RPV, rilpivirine; VL, viral load.

Figure 2.

Crude incidence rate/1000 person-years of follow-up and 95% confidence interval for 2DRs vs 3DRs. Abbreviations: 2DR, 2-drug regimen; 3DR, 3-drug regimen; CVD, cardiovascular disease; ESLD, end stage liver disease; ESRD, end stage renal disease; NADC, non-AIDS–defining cancer; PYFU, person-years of follow-up.

Figure 3.

IRR comparing events on 2DRs vs 3DRs. All events and validated events—adjusted analyses adjusted for age, gender, ethnicity, body mass index, smoking status, human immunodeficiency virus (HIV) risk group, HIV viral load at regimen start, nadir CD4 count, CD4 cell count at regimen start, viral hepatitis C, viral hepatitis B, prior hypertension, prior diabetes, prior AIDS-defining event (excluding cancer), prior AIDS cancer, prior non-AIDS cancer, prior end stage liver disease, prior cardiovascular disease, prior fracture, prior chronic kidney disease, prior dyslipidemia, and number of drugs previously exposed to. Recommended regimens—adjusted analysis adjusted for age, gender, ethnicity, smoking status,CD4 cell count at regimen start, viral hepatitis C, prior AIDS-defining event (excluding cancer), prior non-AIDS cancer, prior cardiovascular disease, prior chronic kidney disease, number of drugs previously exposed to. Recommended regimens included 2DRs: dolutegravir (DTG) plus rilpivirine (RPV), DTG plus lamivudine (3TC), boosted atazanavir (ATV/b) plus 3TC, darunavir (DRV) plus 3TC, DRV plus RPV; 3DRs: DTG or RPV or ATV/b or DRV plus 2 nucleoside reverse transcriptase inhibitors. Abbreviations: 2DR, 2-drug regimen; 3DR, 3-drug regimen; CI, confidence interval; IRR, incidence rate ratio.