Dolutegravir (DTG) is a potent INSTI with high genetic barrier. The once-daily (QD) DTG-3TC combination is attractive, both drugs being safe, highly efficient and convenient.
ANRS 167 LAMIDOL trial is an ongoing open-label, single-arm, multicenter trial assessing the efficacy and tolerance of DTG (50mgQD) – 3TC (300mgQD) in HIV-1 virologically suppressed patients (Pts) on first line cART with 2 NRTIs and either a PI, a NNRTI, or an INSTI. Inclusion criteria were age ≥18yrs, CD4 nadir >200/mm3, normal standard biological parameters, plasma HIV-RNA (pVL)≤50 cps/mL for at least 2 yrs, and wild-type HIV genotype prior to cART initiation (including for INSTI when tested). History of cART modification for intolerance or simplification was allowed. From Wk0 to Wk8 (Phase 1), third agent was switched to DTG, the 2 NRTIs being unchanged. From Wk8 to Wk56 (Phase 2), Pts received QD combination of DTG 50mg-3TC 300mg except if intolerance or pVL>50cps/mL during Phase 1. Virologic failure was defined as pVL>50cps/mL on 2 consecutive samples during Phase 2.
110 Pts were enrolled in Phase 1 in 19 HIV clinics in France from 10/1/2015 to 02/29/2016. Six Pts were not included in Phase 2 (intolerance to DTG in 3 Pts, pVL>50cps/mL in 3 Pts). 104 Pts initiated DTG-3TC combination with following characteristics at inclusion: 86% male, 72% MSM, median age 45yrs (min-max 24-70), 87% stage A, median CD4 nadir 339/mm3 (min-max 203-1155), median time since HIV diagnosis 6.3 yrs (min-max 2.3-24.5), median time on actual cART 4.0 yrs (min-max 0.5-11.3), median CD4 743/mm3 (min-max 373-1115). The baseline regimen contained PI, NNRTI and INSTI in 22%, 58% and 20% Pts, respectively. On 9/26/2016, 103 Pts reached Wk32 corresponding to 24 Wks DTG-3TC combination. No Pt withdrew from study treatment. One protocol-defined virologic failure occurred (pVL=77cps/mL at Wk16) despite adequate plasma C12h of 3TC (299ng/mL) and DTG (2,401ng/mL). Three SAEs occurred in 3 Pts: 2 biological including one 10-fold ALT elevation related to an acute hepatitis C infection and one > 10-fold elevation in creatinine kinase concomitantly with fitness activity, and one depression leading to hospitalization in a Pt with previous psychiatric disorders. DTG-3TC combination was maintained in these 3 Pts with improvement of abnormalities.
When used as 2-drug maintenance therapy, DTG-3TC combination was efficient and well tolerated after 24 Wks of follow-up in highly selected, virologically suppressed Pts.