Durability of dolutegravir plus boosted darunavir as salvage or simplification of salvage regimens in HIV-1 infected, highly treatment-experienced subjects

Figures & data

Table 1 Baseline demographic, immunologic, virologic and therapeutic characteristics of the population, reasons for switching therapy and clinical outcomes.

Parameters of the population, n = 130
Demographic
Age (years), median ± SD	52.0 ± 21.0
Sex (%), M:F	74.6 : 25.4
Caucasians : non caucasians (%)	91.1 : 8.9
Risk factor (%) Male homosexual : heterosexual : intravenous drug abuse	48.5: 26.9: 29.6
Reasons for the switch (%)
Simplification	44.6
Virologic failure	30.0
Toxicity of current regimen	16.9
Poor adherence	4.6
Persistent low-level viremia	3.1
Drug-drug interaction	0.8
Virology
Zenith plasma HIV-1 RNA, log10 copies/mL, median (IQR)	4.9 (4.6 – 5.3)
Over 5 log10 copies/mL at zenith, n (%)	32 (24.6)
Baseline active replication, n (%)	52 (40)
Baseline plasma HIV-1 RNA, log10 copies/mL, median (IQR)	3.1 (2.1 – 3.9)
Over 5 log10 copies/mL at baseline, n (%)	3 (2.3)
Genotypic drug resistance tested, positive (%):	90.8
Towards 1 class : 2 classes : 3 classes : 4 or more classes	89.2 : 75.4 : 70.0 : 9.2
Not tested for historical or technical reasons	9.2
RAMs detected towards NRTIs : NNRTIs : PIs : INSTIs (%)
Reduced baseline sensitivity to DRV, n (%) : to INSTIs, n (%)	20 (15.4) : 12 (9.2)
Immunity:
Zenith CD4+ T-cell count, cells/mmc, (%), median (IQR)	185 (2.0 – 367.0), 10.5 (1.4 – 24.3)
Baseline CD4+ T-cell count, cells/mmc, (%), median (IQR)	526 (329 – 718), 25.0 (17.7 – 33.5)
Therapy:
DRV 800 mg + RTV 100 mg + DTG 50 mg once daily, n (%)	113 (86.9)
DRV 600 mg + RTV 100 mg twice daily + DTG 50 mg once daily, n (%)^a	3 (2.3)
DRV 600 mg + RTV 100 mg + DTG 50 mg twice daily, n (%)^a	12 (9.2)
Clinical outcomes after week 48
Dropout:	1 (cancer)
AEs leading to temporary treatment interruption:	1 (acute hepatitis A)

AE: adverse event; DRV: darunavir; DTG: dolutegravir; INSTI: INtegrase strand transfer inhibitors; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; PIs: protease inhibitors; RAMs: resistance associated mutations; RTV: ritonavir.

* All the patients who had a twice daily regimen had ongoing viral replication before switching.

Figure 1 Immunologic and virologic data at 96 weeks. (A) viral decay, expressed as number of patients in each of the three viral strata: active replication (≥50 HIV-1 RNA copies/mL), containment <50 copies/mL and no virus detected (NVD); (B) mean ± standard deviation values of viremic patients; (C) median ± interquartile range values for absolute CD4+ T-lymphocyte counts/mmc and (D) for % CD4+ T-lymphocytes. (A) NVD = No Virus Detected; (B), (C) and (D) Median + InterQuartile Range.

Figure 2 Evolution of the main routine metabolic parameters. (A) number of subjects presenting any laboratory abnormality ≥ Grade 1 CTCAE []; (B) median triglyceride values; (C) median values of the other metabolic parameters (D) median Total Cholesterol to HDL ratio. ALT: alanine aminoTransferase; AST: aspartate aminoTransferase; eGFR: estimated glomerular filtration rate; HDL-C: high-density lipoprotein; LDL-C: low-density lipoprotein; TC: total cholesterol; TG: triglycerides.