Switching to lamivudine plus darunavir/r dual therapy in a cohort of treatment-experienced HIV-positive patients: the experience of an Italian centre.
BACKGROUND
According to recent evidence about boosted protease inhibitors (PIs/r)-simplified regimens, the combination of 3TC and DRV/r 800/100 mg could represent a feasible option for optimizing antiretroviral therapy (ART) in treatment-experienced HIV+ patients.


METHODS
We retrospectively evaluated patients switching to 3TC+DRV/r, with at least six months of viral suppression, no resistance mutation to DRV or 3TC and not HBV-coinfected: incidence of ART discontinuation and of virological failure (VF: 2 consecutive HIV-RNA determinations>49 cps/mL or a single one≥1000 cps/mL) and the probability of remaining discontinuation-free during one-year follow-up (FU), as well as changes in laboratory parameters at 1, 3, 6 and 12 months were estimated.


RESULTS
We included 94 patients: 74 males, mostly MSM (39.4%), with 49 years old, 9 years of HIV disease, 8 years of ART (median values). Median nadir CD4 count and zenith viral load (log10) were 194 cells/µL and 4.90, respectively. Ten patients were HCV-coinfected and 38 had at least a previous VF. Seventy-four patients were on an NRTIs-based triple regimen (mainly TDF/FTC or 3TC/ABC) whereas 14 on another PI-based dual therapy (mainly LPV/r). Incidence of treatment discontinuation was 12.4 per 100 patients-year follow-up (PYFU), but only 2 patients experienced a VF (3.5 per 100 PYFU). Mean time free from discontinuation was 5 years (95% CI 4-6), with a cumulative one-year estimated probability of staying on 3TC+DRV/r of 85.9%. At three months, a trend of increased CD4 cells count (+42 cells/µL, p 0.059) was observed, but not confirmed at later time point; an increase of total cholesterol (TC, +17mg/dL, p 0.008) and LDL (+19 mg/dL, p 0.002), and a decreased level of AST and ALT (-2 UI/L, p 0.045; -5 UI/L, p 0.009, respectively) were also detected. Total bilirubin was reduced (-0.71 mg/dL, p 0.038). At 6 and 12 months, alteration of lipid profile was similar, with also an increased TC/HDL ratio (+0.48, p=0.030, at six months) and HDL/LDL ratio (-0.04, p=0.035, at 12 months). A significant decrease in ALT levels (-6 UI/L, 0.013) and a diminishing trend for AST and total bilirubin, as well as a significant increase in renal function (GFR +4mL/min, p 0.048) were observed at 12 months.


CONCLUSIONS
These observations on 3TC+DRV/r-based dual therapy simplification in virologically suppressed patients show a good profile of efficacy and safety. An extended FU time is needed in order to establish the real impact of this promising therapeutic choice.
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Alberto
A
Borghetti
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Annalisa
A
Mondi
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Benedetta
B
Piccoli
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Roberta
R
Gagliardini
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Silvia
S
Lamonica
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Nicoletta
N
Ciccarelli
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Alessandro
A
D'Avino
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Federico
F
Pallavicini
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Roberto
R
Cauda
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Andrea
A
De Luca
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Massimiliano
M
Fabbiani
Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy.
Simona
S
Di Giambenedetto