Doravirine/islatravir was found to be non-inferior to continuing bictegravir/F/TAF in maintaining viral suppression. Simplification to F/TDF following induction with INSTI + 2 NRTIs resulted in similar virologic suppression rates, CD4 gains, and changes in body weight compared to dolutegravir/3TC. Low-level viremia was associated with subsequent virologic failure in a dose-dependent manner. Causes of death in people with HIV have shifted from HIV/AIDS-related to non-AIDS cancers as treatment has improved and patients live longer.

1. Independent Coverage from the
2023 European AIDS Clinical Society (EACS) Conference
Copyrighted 2023 by Practice Point Communications, unless otherwise noted. All rights reserved.

2. Faculty
• Nothing to disclose
William Powderly, MD
J. William Campbell Professor of Medicine
Larry J. Shapiro Director of Institute of Public Health
Washington University in St. Louis
St. Louis, MO

3. Upon completion of this activity, participants should be better able to:
• Review the latest advances in the prevention and treatment of HIV and related
comorbidities
Learning Objective (AMA/ANCC/ACPE)

4. Study 018:
Switch to Doravirine/Islatravir From Bictegravir/F/TAF
Phase 3, noninferiority
HIV RNA <50 copies/mL for ≥3 months
with bictegravir/F/TAF
No history of treatment failure
No known resistance to doravirine
No active HBV infection
Bictegravir/F/TAF
(n=319)
Doravirine/Islatravir 100/0.75 mg qd
(n=322)
Week 0 48 96
Primary Endpoint
Virologic Failure
(HIV RNA ≥50 copies/mL)
Non-inferiority margin (4%).
Baseline characteristics:
Age (median): 48 years.
Male: 72%.
BMI: 26 kg/m2.
Prior ART duration: 14-15 months.
CD4: 645-704 cells/µL. Paredes R, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS1.01.
Current
Analysis

5. Study 018:
Outcomes at Week 96
• HIV RNA ≥50 copies/mL
(FDA snapshot)
– Doravirine/islatravir was non-inferior to
continuing bictegravir/F/TAF
– No doravirine or islatravir resistance observed
• Generally well tolerated
• Decreased CD4 count and/or total
lymphocytes with doravirine/islatravir
compared with continuing
bictegravir/F/TAF
Patients
(%)
Virologic Outcomes at
Week 96 (FDA Snapshot)
0
20
40
60
80
100
HIV RNA
≥50 Copies/mL
<1% <1%
85%
91%
HIV RNA
<50 Copies/mL
Switch to DOR/ISL
(n=322)
Continue bictegravir/F/TAF
(n=319)
Difference:
0.3 (-1.2 to -2.0)
Difference:
-6.1 (-11.3 to -1.1)
Paredes R, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS1.01.

6. ANRS ALTER Study:
Drug Reduce From 3-Drug ART to Dual NRTI Regimen
Phase 2, noninferiority
Open-label
Treatment-naïve
HIV RNA <50K copies/mL
CD4 >300 cells/μL
INSTI + TDF/XTC
(n=23)
Dolutegravir/3TC
(n=22)
Week 0 24 48
Primary
Endpoint
XTC: emtricitabine or lamivudine.
Primary endpoint: HIV RNA <50 copies/mL at week 48 (ITT, FDA snapshot).
Non-inferiority margin (10%).
Baseline characteristics:
Age (median): 32 years.
Male: 84%.
HIV RNA: 4.1 log10 copies/mL.
CD4: 520 cells/µL.
BMI: 22 kg/m2. Katlama C, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS1.03.
F/TDF
Current
Analysis

7. ANRS ALTER Study:
Outcomes at Week 24
• Simplification to F/TDF following induction
with INSTI + 2 NRTIs compared with
dolutegravir/3TC in this patient population
resulted in
– Similar virologic suppression rates
– Similar CD4 gains
– Similar changes in body weight and BMI
Patients
(%)
Virologic Outcomes at
Week 24 (ITT, FDA Snapshot)
0
20
40
60
80
100
HIV RNA
<50 Copies/mL
5% 4%
86% 87%
HIV RNA
≥50 Copies/mL
Dolutegravir/3TC (n=22)
Delayed dual NRTI (n=23)
Adverse
Events
0% 0%
XTC: emtricitabine or lamivudine. Katlama C, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS1.03.

8. HIV Swiss Cohort:
Impact of Low-Level Viremia on ART
• Longitudinal observational cohort study of a heterogenous population of PWH on
ART (2000-2023; n=8132)
– HIV RNA measurements (n=169,352)
– 49,582 person-years of follow-up
– Virologic failure: 8%
– Low-level viremia: 21%
• Key results
– Low-level viremia was associated with subsequent virologic failure: HR 3.5 (95% CI 2.2, 5.7)
– Clear dose dependency of low-level viremia categories
– Sensitivity analyses confirm results as robust
Low-level viremia:
50-200 copies/mL in ≥2 HIV RNA measurements >90 days apart. Kusejko K, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS1.02.

9. HIV Swiss Cohort:
Trends in Causes of Death in PWH
• Longitudinal observational cohort study (2005-2022)
– Number of deaths (n=1630)
– Change in median of age of death: 44 yo 61 years of age
• Key results during 2020-2022 versus 2006-2010
– HIV/AIDS-related deaths declined 5-fold
– Liver-related deaths declined 7-fold
– CVD/heart-related deaths remained stable
– Non-AIDS, non-hepatic cancer deaths increased 2-fold
Weber SR, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract OS1.01.

10. 10
ATHENA National Cohort: Real-World Experience With Long-
Acting Injectable Cabotegravir + Rilpivirine
• Observational study of PWH initiating long-acting injectable cabotegravir + rilpivirine (2018-2023;
n=619)
– Controls (n=1238)
• INSTI 3-drug ART (53%), NNRTI 3 drug ART (27%), 2-drug ART (16%), PI-based ART (5%)
• Virologic failure
– Long-acting injectable cabotegravir + rilpivirine: 0.9%
– Controls: 1.8%
• Switching to long-acting injectable cabotegravir + rilpivirine was not associated with an increased
risk of virological failure versus standard oral ART
Jongen V, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS8.01.
Wensing A, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract PS8.03.

11. 11
DOMINO and DYNAMIC:
HIV Maturation Inhibitor + 2 NRTIs in Treatment-Naïve PWH
• Two, phase 2b studies
– DOMINO: GSK3640254 (100, 150, 200 mg qd) versus dolutegravir (both with either ABC/3TC or F/TAF)
– DYNAMIC: GSK3640254 (100, 150, 200 mg qd) + dolutegravir versus dolutegravir/3TC
• HIV RNA <50 copies/mL at week 24
– DOMINO
• GSK3640254 (100, 150, 200 mg qd) + ABC/3TC or F/TAF: 76%-91%
• Dolutegravir + ABC/3TC or F/TAF: 92%
– DYNAMIC
• GSK3640254 (100, 150, 200 mg qd) + dolutegravir: 77%-95%
• Dolutegravir/3TC: 86%
• Results support investigation of the next maturation inhibitor
– Clinical development of GSK3640254 ended
Joshi SR, et al. 19th European AIDS Conference. Warsaw, 2023. Abstracts RA2.01 and RA2.02.

12. 12
Impact of HBcAb Positivity on Virologic Outcomes After Switch
to Dolutegravir/3TC
Retrospective cohort of PWH
HBsAg negative populations
HBcAb negative/positive
HIV RNA <20 copies/mL on ART for 2 years
HBcAb Negative
(n=191)
HBcAb Positive
(n=76)
Month 0 36
Baseline characteristics:
Age (median): 41 years.
Male: 68%.
Nadir CD4: 306 cells/μL.
ART pre-switch:
PI /NNRTI/INSTI + 2NRTIs: 15%/33%/47%.
Previous HIV viral rebound: 17%. Malagnino V, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract RA2.07.
Current
Analysis
Switch to Dolutegravir/3TC

13. 13
Impact of HBcAb Positivity on Virologic Outcomes After Switch
to Dolutegravir/3TC
• Approximately one third of the HBcAb-positive patients who switched to dolutegravir/3TC were not
completely suppressed (HIV RNA <20 copies/mL) during the 36-month follow-up
• Risk of not maintaining HIV RNA suppression
– HBcAb positivity: 2-fold increase in risk (P<0.005)
• Need for additional prospective studies
– Identify all risk factors associated with suboptimal HIV suppression
Malagnino V, et al. 19th European AIDS Conference. Warsaw, 2023. Abstract RA2.07.

14. 14
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