Dolutegravir as monotherapy in HIV-1-infected individuals with suppressed HIV viraemia.
Reducing drug burden is a key challenge for achieving lifelong suppressive HIV therapy. Dolutegravir, with a high potency, long half-life and high genetic barrier, offers potential for monotherapy.



This observational single-centre study enrolled all patients with HIV RNA (viral load) <50 copies/mL for at least 12 months, with CD4 >350 cells/mm(3) and with no failure under integrase inhibitor therapy who had switched from suppressive ART to dolutegravir monotherapy (50 mg/day). Primary outcome was proportion of patients with viral load <50 copies/mL at week 24.



Twenty-eight patients treated for a median ART duration of 17 years (IQR 11-20), virally suppressed for a median of 79 months (IQR 42-95) and with a median CD4 count of 624 cells/mm(3) (IQR 524-761), were enrolled. Baseline ART consisted of a three-drug (n = 10), two-drug (n = 10) or single-drug (n = 8) regimen with integrase inhibitor exposure in 13 patients. The proportion of patients maintaining viral load <50 copies/mL was 96% (95% CI 79%-100%) at week 4, 100% (95% CI = 85%-100%) at week 8, 93% (95% CI 76%-99%) at week 12 and 92% (75-99) at week 24. Three patients (3.70%; 95% CI 3.4%-10.8%) with prior integrase inhibitor experience had HIV RNA rebound with the presence of resistance mutations. Genotyping of HIV DNA using the Sanger method or ultradeep sequencing showed no integrase inhibitor resistance-associated mutations (RAMs) except for the mutation 74I in a patient on a suppressive elvitegravir regimen. The median within- and between-subject variability of dolutegravir C24 was 25% and 34%, respectively. Nine patients with a year of follow-up remained virally suppressed.



Dolutegravir has the potency to be further investigated as a single ART in randomized studies, particularly in patients with no prior exposure to integrase inhibitors.
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France christine.katlama@aphp.fr.
C
C
Katlama
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France Hôpital Pitié-Salpêtrière, Department of Virology, Paris, France.
C
C
Soulié
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France.
F
F
Caby
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France.
A
A
Denis
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France.
C
C
Blanc
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France.
L
L
Schneider
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France.
M-A
MA
Valantin
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France.
R
R
Tubiana
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France.
M
M
Kirstetter
Hôpital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France.
E
E
Valdenassi
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France Hôpital Pitié-Salpêtrière, Department of Virology, Paris, France.
Thuy
T
Nguyen
Pharmaco-Toxicology Department, APHP, Bichat-Claude Bernard Hospital, Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France.
G
G
Peytavin
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France Hôpital Pitié-Salpêtrière, Department of Virology, Paris, France.
V
V
Calvez
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France Hôpital Pitié-Salpêtrière, Department of Virology, Paris, France.
A-G
AG
Marcelin
D000328:Adult; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D019562:Viral Load; D000099226:Dolutegravir
D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099226:Dolutegravir