External Comparison of Ibalizumab in Trials vs. Other Regimens in OPERA

Study Overview
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Brief Summary
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Among heavily treatment experienced people living with HIV, the virologic effectiveness of ibalizumab + optimized background regimen from two clinical trials will be compared to non-ibalizumab-containing regimens in routine clinical care in the OPERA cohort.

Detailed Description
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The US Department of Health and Human Services (DHHS) HIV treatment guideline suggest that ibalizumab may be considered in the context of multidrug resistance without fully active ART options. However, clinical trials assessing ibalizumab efficacy did not include an active comparison arm in which participants did not receive ibalizumab. The use of external controls can provide valuable information and context to interpret the results of clinical trials when randomization to a control arm cannot be performed. The OPERA (Observational Pharmaco-Epidemiology Research & Analysis) cohort, a large US electronic health record database, is well suited for this as the OPERA and trials populations arose from the same geographic location (i.e., US). An external comparison of ibalizumab + optimized background regimen from trials vs. non-ibalizumab containing regimens in routine clinical care in the OPERA cohort may confirm results from prior studies suggesting viral control benefits of ibalizumab.

Official Title
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External Comparison of Effectiveness of Ibalizumab in Clinical Trials vs. Other HTE Regimens in OPERA

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Ibalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Trial IBA+OBR group): Participant in TMB-202 or TMB-301/311 Received 800 mg IBA every 2 weeks, with or without a loading dose Inclusion Criteria (OPERA non-IBA OBR group): HIV-1 infection 18 years or older Heavily treatment experienced (i.e., ever on a regimen containing either DTG BID or DRV BID) Documented resistance to ≥1 ARV from each of three ARV classes Genotype information available for all the relevant gene regions (see Table 2) Viral load > 200 copies/mL at index regimen initiation Not pregnant at index No new AIDS defining event within 3 months before/on index (except cutaneous Kaposi's sarcoma or HIVAW) No new cancer diagnosis within 12 weeks before/on index No IBA prescribed prior to/with the index regimen Index regimen does not include cabotegravir, fostemsavir, investigational drugs Viral sensitivity/susceptibility to at least one ARV in the index regimen Baseline VL available (within 6 months before/at index) Baseline CD4 available (within 6 months before/at index) ≥1 VL measurement at any time after index

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IBA+OBR (trials)<br>Participants in TMB-202 or TMB-301/311 trials who received 800 mg ibalizumab every 2 weeks, with or without a loading dose | Drug: Ibalizumab<br>* Participation in clinical trials vs. routine care in OPERA<br>* Other names: Regimens not containing ibalizumab;|
| Non-IBA+OBR (OPERA)<br>Heavily treatment experienced adults living with HIV in care in OPERA, with documented resistance to ≥1 ARV from each of three ARV classes switching to a new regimen that does not include ibalizumab | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral suppression | Viral load <200 copies/mL | Week 24 | 
| Viral suppression | Viral load <200 copies/mL | Week 48 | 
| Viral suppression | Viral load <200 copies/mL | Week 60 | 
| Viral suppression | Viral load <200 copies/mL | Week 96 | 
| Viral undetectability | Viral load <50 copies/mL | Week 24 | 
| Viral undetectability | Viral load <50 copies/mL | Week 48 | 
| Viral undetectability | Viral load <50 copies/mL | Week 60 | 
| Viral undetectability | Viral load <50 copies/mL | Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heavily treatment experienced, External comparison, Ibalizumab, Virologic effectiveness