Dolutegravir Plus Lamivudine as a Switch Strategy

Discussion

In our multicenter cohort of virologically suppressed PLWHIV switched to DTG + 3TC, we were able to assess the efficacy, safety, and overall tolerability of this 2DR in the long period. It has been been over 5 years that DTG + 3TC has been introduced in clinical practice as a feasible switch strategy, and results from this study appear in line with the results from clinical trials^[10] and other observational studies, including previous results from our cohort.^[8,9] Compared with patients enrolled in the TANGO study, our cohort is composed of older patients, with a longer history of HIV and ARV, and over one-fifth of the analyzed patients have experienced at least 1 VF; these differences further reinforces the strength of this combination in the real-life setting.

In this work, we observed a low VF rate (0.9 VF per 100 PYFU), with no patient experiencing the emergence of resistance mutation at failure, reflecting the safety and high genetic barrier of dolutegravir. Moreover, confirming previous findings,^[13] we did not observe an overall increase in the VF rate in patients with the M184V resistance mutation, but those with a reduced time of virological suppression at baseline showed an increased risk of VF in the presence of M184V.

In patients discontinuing study regimen, toxicity remained the leading cause of treatment interruption,^[8] with most events being of neuropsychological nature. The previously observed correlation between neuropsychiatric disorders and HCV coinfections was confirmed.^[8,14]

Our study has some limitations, such as its retrospective nature, the lack of a control group, and the lack of recording of data on patients' compliance or minor adverse events not leading to TD. Other limitations are the low number of patients with available information regarding previous M184V mutation and the wide confidence intervals for some of the findings. However, the study also presents several strengths, including its long follow-up time, its sample size, and the real-life setting.

In conclusion, DTG+3TC confirmed its efficacy in maintaining virological suppression in a large proportion of PLWHIV in a real-life setting; clinicians should always consider patients' clinical and viro-immunological history when considering the switch to a dual regimen.

Table 1. Patients' Characteristics at Baseline (N 785)
Variables
Age (yr), median (IQR)	52.3 (44.9–58.2)
Female, n (%)	231 (29.4)
Risk factor for HIV infection, n (%):
Heterosexual	319 (40.6)
MSM	305 (38.9)
IDU	119 (15.2)
Others	42 (5.3)
Anti-HCV antibodies positive, n (%)	64 (8.2)
Time from HIV diagnosis (yr), median (IQR)	14.9 (8.0–22.0)
CDC stage C, n (%)	132 (16.8)
Time on antiretroviral therapy (yr), median (IQR)	11.5 (5.9–18.6)
Nadir of CD4⁺ (cell/μL), median (IQR)	225 (96–331)
Zenith HIV-RNA (log copies/mL), median (IQR)	4.94 (4.39–5.45)
Zenith HIV-RNA > 500.000 copies/mL, n (%)	110 (14.0)
Previous virological failure, n (%)	175 (22.3)
CD4⁺ count (cell/μL), median (IQR)	680 (500–889)
Time of virological suppression (mo), median (IQR)	29.1 (14.6–49.5)
M184V resistance mutation, n (%)
Present	33 (4.2)
Absent	214 (27.3)
Unknown	538 (68.5)
Previous HAART regimen, n (%):
2NRTIs + NNRTI	180 (22.9)
2NRTIs + PI or b/PI	92 (11.7)
2NRTIs + INI	216 (27.5)
Dual therapy	268 (34.1)
Other	29 (3.7)
HIV subtype B, n (%)	91 (11.6)
FTC/TDF in previous regimen, n (%)	253 (32.3)
DTG in previous regimen, n (%)	147 (18.7)
3TC + PI in previous regime, n (%)	216 (27.5)
Reasons for switch, n (%):
Simplification	302 (38.5)
Dyslipidemia	96 (12.2)
Gastrointestinal or liver toxicity	49 (6.2)
Renal toxicity	32 (4.1)
Osteoporosis	27 (3.4)
Neurological toxicity	6 (0.8)
Other toxicities	28 (3.6)
Drug–drug interactions	50 (6.4)
Cardiovascular risk	21 (2.7)
Other/unknown reasons	174 (22.2)

Table 1. Patients' Characteristics at Baseline (N 785)

Variables

Age (yr), median (IQR)

52.3 (44.9–58.2)

Female, n (%)

231 (29.4)

Risk factor for HIV infection, n (%):

Heterosexual

319 (40.6)

MSM

305 (38.9)

IDU

119 (15.2)

Others

42 (5.3)

Anti-HCV antibodies positive, n (%)

64 (8.2)

Time from HIV diagnosis (yr), median (IQR)

14.9 (8.0–22.0)

CDC stage C, n (%)

132 (16.8)

Time on antiretroviral therapy (yr), median (IQR)

11.5 (5.9–18.6)

Nadir of CD4⁺ (cell/μL), median (IQR)

225 (96–331)

Zenith HIV-RNA (log copies/mL), median (IQR)

4.94 (4.39–5.45)

Zenith HIV-RNA > 500.000 copies/mL, n (%)

110 (14.0)

Previous virological failure, n (%)

175 (22.3)

CD4⁺ count (cell/μL), median (IQR)

680 (500–889)

Time of virological suppression (mo), median (IQR)

29.1 (14.6–49.5)

M184V resistance mutation, n (%)

Present

33 (4.2)

Absent

214 (27.3)

Unknown

538 (68.5)

Previous HAART regimen, n (%):

2NRTIs + NNRTI

180 (22.9)

2NRTIs + PI or b/PI

92 (11.7)

2NRTIs + INI

216 (27.5)

Dual therapy

268 (34.1)

Other

29 (3.7)

HIV subtype B, n (%)

91 (11.6)

FTC/TDF in previous regimen, n (%)

253 (32.3)

DTG in previous regimen, n (%)

147 (18.7)

3TC + PI in previous regime, n (%)

216 (27.5)

Reasons for switch, n (%):

Simplification

302 (38.5)

Dyslipidemia

96 (12.2)

Gastrointestinal or liver toxicity

49 (6.2)

Renal toxicity

32 (4.1)

Osteoporosis

27 (3.4)

Neurological toxicity

6 (0.8)

Other toxicities

28 (3.6)

Drug–drug interactions

50 (6.4)

Cardiovascular risk

21 (2.7)

Other/unknown reasons

174 (22.2)

Authors and Disclosures

Arturo Ciccullo, MD^a,b, Vanni Borghi, MD^c, Andrea Giacomelli, MD^d, Maria Vittoria Cossu, MD^e, Gaetana Sterrantino, MD^f, Alessandra Latini, MD^g, Andrea Giacometti, MD^h, Andrea De Vito, MDⁱ, William Gennari, MD^j, Giordano Madeddu, MDⁱ, Amedeo Capetti, MD^e, Gabriella d'Ettorre, MD^k, Cristina Mussini, MD^c, Stefano Rusconi, MD^d, Simona Di Giambenedetto, MD^b,l and Gianmaria Baldin, MD^l,m

^aUOC Malattie Infettive, P.O. San Salvatore, L'Aquila, Italy; ^bCatholic University of the Sacred Heart, Rome, Italy; ^cAzienda Ospedaliero Universitaria di Modena, Clinica Malattie Infettive e Tropicali, Modena, Italy; ^dInfectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, Milan, Italy; ^eDivision of Infectious Diseases, Department of Infectious Diseases, Luigi Sacco University Hospital, Milan, Italy; ^fInfectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy; ^gInfectious Dermatology and Allergology Unit, IFO S. Gallicano Institute (IRCCS), Rome, Italy; ^hClinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona. Italy; ⁱUnit of Infectious Diseases, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy; ^jAzienda Ospedaliero Universitaria di Modena Laboratorio di Microbiologia e Virologia, Modena, Italy; ^kDepartment of Public Health and Infectious Diseases, Azienda Policlinico Umberto I, Rome, Italy; ^lUOC Malattie Infettive, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; and ^mMater Olbia Hospital, Olbia, Italy.

Correspondence to
Arturo. Ciccullo, MD, UOC Malattie Infettive, P.O. San Salvatore, via Lorenzo Natali 1, L'Aquila (AQ) 67100, Italy (e-mail: arturo.ciccullo@gmail.com).

A. Ciccullo received travel grants from ViiV Healthcare. A.G. reports grants and/or personal fees from BMS, Gliead, Janssen, MSD and ViiV Healthcare. A. Capetti has received a personal grant from AB, Gilead, and ViiV. G.S. has received funds for speaking by Gilead, Merck, Janssen, AbbVie, and ViiV. C.M. has participated in advisory boards and received study grants and/or speaker honoraria from AbbVie, Gilead, ViiV, Janssen, Angelini, BMS, and MSD. S.R. received research grants to his institution from ViiV Heathcare, Gilead Sciences, and Janssen, outside the submitted work; he was also a paid consultant for ViiV Heathcare, Gilead Sciences, Merck Sharp & Dohme, Bristol-Myers Squibb, and Janssen. S.D.G. was a paid consultant or member of advisory boards for Gilead, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme, and Bristol-Myers Squibb. The remainig authors have no conflicts of interest to disclose.