Real Life Experience of Dolutegravir and Lamivudine Dual Therapy As a Switching Regimen in HIVTR Cohort

Transcription

1 Real Life Experience of Dolutegravir and Lamivudine Dual Therapy As a Switching Regimen in HIVTR Cohort Yagci-Caglayik D 1, Gokengin D 2, Inan A 3, Ozkan-Ozdemir H 4, Inan D 5, Akbulut A 6, Korten V 1, HIVTR Cohort 1 Marmara University, Pendik Training and Research Hospital, Infectious Diseases and Clinical Microbiology, İstanbul, Turkey, 2 Ege University, Infectious Diseases and Clinical Microbiology, İzmir, Turkey, 3 Saglik Bilimleri University, Haydarpasa Training and Research Hospital, Infectious Diseases and Clinical Microbiology, İstanbul, Turkey, 4 Bozyaka Training and Research Hospital, Infectious Diseases and Clinical Microbiology, İzmir, Turkey, 5 Akdeniz University, Infectious Diseases and Clinical Microbiology, Antalya, Turkey, 6 Firat University, Infectious Diseases and Clinical Microbiology, Elazig, Turkey

2 Objectives Several studies suggested dolutegravir (DTG) monotherapy or once daily DTG lamivudine (3TC) combination might be an attractive switch regimen in virologically suppressed patients, but data are still limited. This study reports our experience on DTG-3TC as a dual therapy switch regimen in a real life setting.

3 Methods HIV1 infected patients receiving DTG-3TC for at least 3 months were systematically identified in the HIVTR Cohort. Antiretroviral therapy (ART) naïve patients were excluded. Virologic and immunologic parameters, reasons for switch, duration of HIV infection, available drug resistance results, ART regimens used and duration of suppression before switch were recorded.

4 Methods-2 The primary outcome was the proportion of patients who maintained virologic suppression (HIVRNA < 50 copies/ml) at the last follow-up visit. Adverse events after switch were recorded. Proximal Renal Tubule Dysfunction (PRTD) was defined as the presence of > 2 of the following: proteinuria, glycosuria, phosphaturia or uricosuria with or without renal impairment. Baseline Chronic Kidney Disease (CKD) was defined as 2 consecutive estimated glomerular filtration rate (egfr) <60 ml/min/1.73 m 2 with at least 3 months interval.

5 Results-1 Twenty-nine out of 32 patients from 6 centers were virologically suppressed before switch and none of them had experienced virologic failure with prior regimens. Table 1 shows baseline characteristics of the patients.

6 Table 1. Results-1 Baseline characteristics of 32 patients before switch. Age, median (IQR), years 54 ( 41-64) Male, n (%) 27 (84) Median (IQR) duration of HIV infection (years) 4,5 (3,0-9,0) CD4 count nadir (cells/mm3), median (IQR) 272 ( ) Hepatitis coinfection (n) Duration of plasma viral load (PVL) < 50 copies/ml before switch (months), median (IQR) n:29 Chronic hepatitis B (n=4), Chronic hepatitis C (n=1) 24 (7-67) Prior ART regimens number, median (IQR) 2 (2-3) Patients number, GFR (CKDEPI)< 60 ml/min/1.73 m², n(%) Prior genotypic drug resistance mutations (n:3 /10 available tests) 13 (40) 1. M41L+K65R+K70T 2. K65R+K70S 3. M41L Prior antiretroviral drugs before switch, n(%) PI=16 (50) (DRV/r=3, LPV/r=13); NNRTI=4 (13)(EFV=4); INSTI=17 (53) (RAL=7, DTG=7,EVG=3); TDF/FTC=21 (66) 3TC=8 (25)(AZT-3TC=6) INSTI: integrase strand transfer inhibitor, NNRTI: Nonnucleoside reverse transcriptase inhibitor, PI: Protease inhibitor, 3TC: lamivudine, AZT: zidovudine, DRV/r: darunavir/ritonavir, DTG: dolutegravir, EFV: efavirenz, EVG: elvitegravir, LPV/r: lopinavir/ritonavir, RAL: raltegravir, TDF/FTC: tenofovir disoproxil fumerate /Emtricitabine

7 Results-2 Duration of suppression was > 6 months for 27 patients and 2 patients were suppressed for only 3 months. Median duration of suppression (range) was 24 months (3-110 months). Three patients had HIV-RNA levels 21503, 656 and 59 copies/ml before switch. CD4 T cell counts before switch were > 200 cells/mm 3 in all patients except one (90 cells/mm³). Reasons for switch to DTG-3TC were; documented renal toxicity or impaired renal function (21), hyperlipidemia (6), osteoporosis (6), prevention of potential toxicities (n=2), regimen simplification (n=4), and adverse events (diarrhea=1, lipodystrophy=1), as presented in Table-2a, 2b.

8 Main reasons for switch Number of patients (n=32) All reasons for switch (n=41) (a patient may have more than one reason) Documented renal toxicity or impaired renal function Regimen simplification 4 4 Hyperlipidemia 3 6 Osteoporosis 2 6 Prevention of lipodystrophy 1 2 Lipodystrophy 1 1 Diarrhea 0 1 Table-2a Reasons for switching to DTG-3TC

9 Documented renal toxicity or impaired renal function type Number (n=21) egfr (CKD-EPI) change, ml/min (before and after switch) PRTD with renal dysfunction 2 +2, +9 without renal dysfunction 6-17,-11,-5, 0, +1, +8 CKD drug related 3 +1,+10,+12 not drug related 10-4,-4, -3, 0,0,+3,+3, +6, +15, +25 Table-2b Types of renal diseases leading to switch and improvement of renal function after switch.

10 Three patients had a prior resistance test with NRTI drug resistance mutations before switch Prior NRTI resistance mutations M41L, K65R, K70T (HBV co-infected) K65R, K70S M41L Prior ART regimens Duration of supression (months) LPV/r+RAL 30 Reasons for switch Duration of 3TC+DTG (wks.) Hyperlipidemia +CKD 40 AZT-3TC+LPV/r 12 Lipodystrophy 80 TDF-FTC+DTG 6 Osteoporosis 16 Table-3-Characteristics and follow-up of patients with prior NRTI resistance

11 Results-3 Baseline egfr values of 13 patients were <60mL/min before switch, 3 of these patients reached egfr levels >60 ml/min after switch. Seven patients with egfr < 50 ml/min were given 3TC doses adjusted for creatinine clearance (150mg/day) during follow-up. One patient had elevation of creatinine levels up to 1,3 mg/dl with a normal cystatin-c level (0,9 mg/dl), suggesting a reduction of tubular secretion of creatinine due to DTG.

12 Results-4 There was a modest reduction in cholesterol, triglyceride and LDL levels and an increase in HDL levels after switch, not reaching statistically significant levels. No patient experienced a serious adverse event, AIDS related events, or died during the follow-up period. Moderate elevation of liver enzymes was observed in a patient with chronic hepatitis B, not leading to discontinuation of the regimen.

13 Conclusion When used as dual therapy, DTG-3TC combination was efficient and well tolerated after a median duration of 30 weeks of follow up in virologically suppressed patients. Longer follow up of a higher number of patients is needed for comparison of DTG-3TC with other switch regimens for long term virologic suppression and adverse event rates.