DTG Plus DRV /Cobicistat in Treatment Experienced Resistant HIV-1-Infected Patients
Introduction
In extensively treatment experienced and multidrug resistant HIV-1 patients, maintaining lifelong HIV-1 suppression is crucial thus there is need for simple, effective, and well-tolerated antiretroviral therapy (ART) combinations. Darunavir (DRV) boosted with ritonavir (DRV/r) or cobicistat (DRV/c) and dolutegravir (DTG) have demonstrated efficacy in patients with limited therapeutic options.
Aim
To evaluate efficacy and safety of DTG plus DRV/c as a once-daily maintenance strategy vs continuing the previous ART in patients who were highly treatment experienced with HIV-1 resistant to drugs but not integrase inhibitors (INSTIs) or DRV
Patient profile
- HIV-infected adultswith confirmed HIV-1 RNA <50 copies/mL for >6 months
- Prior treatment with at least 3 antiretroviral drugs
- History of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to DRV and integrase inhibitors
Methods
- Randomized, open label, noninferiority, multicentre study.
- The primary endpoint was the proportion of patients with HIV-1 RNA 50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%
- Virologic failure was defined as confirmed HIV-1 RNA >50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation.
Results
- No significant differences in virologic efficacy in the Time to loss of virologic response (TLOVR) or FDA snapshot analyses
Figure 1 Virological outcomes at week 48 as per TLOVR or FDA snapshot analysis
- In SOC group, 2 virologic failures vs none was observed in the 2D group.
- Three and 5 participants in the 2D and SOC groups experienced blips during the follow-up period (P=.480)
- At 48 weeks, mean ART adherence was similar between groups (100% in the 2D group vs 99.6% in the SOC group, P= .334)
- At week 48, median CD4+ change from baseline in cell/mm3 count was -1.0 cells/mm3 in the 2D arm and 0.4 cells/mm3 in the SOC arm (P=.130)
Table 1: Mean changes in Lipids, Creatinine
|
|
SOC group (Control; n = 44) |
2D group (DRV/c + DTG; n = 45) |
P Value |
|||||
|
Cholesterol, mg/dL |
Baseline |
Week 48 |
P-valuea |
Baseline |
Week 48 |
P-valuea |
Baseline |
Week 48 |
|
Total |
198.0
|
205.8
|
.530 |
194.6
|
200.0
|
.560 |
.510 |
.429 |
|
LDL |
128.0
|
126.3
|
.498 |
119.0
|
119.0
|
.660 |
.323 |
.511 |
|
HDL |
47.0
|
44.4
|
.120 |
47.3
|
48.3
|
.424 |
.826 |
.429 |
|
Triglycerides, mg/dL |
133.0
|
152.0
|
.236 |
125.7
|
136.0
|
.666 |
.743 |
.233 |
|
Creatinine, mg/dL |
0.86
|
0.90
|
.355 |
0.90
|
0.99
|
.003 |
.582 |
.176 |
|
CKD-EPI, mL/min |
80.0
|
74.1
|
.414 |
76.3
|
76.0
|
.012 |
0.370 |
.927 |
- At least 1 adverse event was reported in 91.1% in 2 D group vs 72.7% in SOC group.
- In 2D arm, a total of 111 adverse events were reportedvs 81 in the SOC arm (P= .002)
- No serious adverse events, AIDS-defining events, or deaths were reported during the study.
Conclusion
- In highly treatment experienced patients with resistance to at least 2 antiretroviral classes but fully active DRV and INSTIs, dual therapy with DRV/c plus DTG maintains viral suppression in patients who are well suppressed and adherent to ART.
- DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients.
Reference
Open Forum Infect Dis. 2023 Oct 31;10(11):ofad542
