Dolutegravir Plus Lamivudine as First-Line Regimen in a Multicenter Cohort of HIV-1-Infected Patients: Preliminary Data from Clinical Practice

Abstract

Editor: The results from the ACTG 5353 trial¹ and GEMINI trials² have demonstrated the efficacy of a dual therapy with dolutegravir plus lamivudine as first-line regimen in treatment-naive HIV-positive patients. This regimen, already closely evaluated as a switch option in treatment-experienced patients, for whom it has shown a good tolerability profile and a high virological efficacy in the long term,^3,4 is increasingly becoming a promising option for the treatment of a large portion of HIV-infected patients.

We would like to present the preliminary data from a multicenter study on antiretroviral therapy (ART)-naive patients starting lamivudine plus dolutegravir in clinical practice. At baseline and at each follow-up visit viroimmunological markers of HIV infection, including plasma HIV-RNA level, were collected (quantitative assay, detection limit of 37 copies/mL). We evaluated the proportion of patients reaching virological suppression (defined as HIV-RNA <50 copies/mL) during follow-up time. The study was approved by each local ethics committee (promoting center protocol number: 5284/15) and all patients signed an informed consent.

We enrolled 10 patients: 6 (60%) men, with a median age of 50 years (interquartile range [IQR] 30–55). At baseline, median HIV-RNA was 4.84 log₁₀ copies/mL (IQR 4.64–4.96), whereas median CD4+ cell count was 342 cell/mm³ (IQR 301–419). Two patients presented a peak HIV-RNA >100,000 copies/mL.

One patient, with a peak HIV-RNA of 55,833 copies/mL, after 3 weeks from ART initiation, achieved a HIV-RNA of 104 copies/mL, but no following virological determinations are at the moment available. The other nine patients reached 8 weeks of follow-up; among them, eight reached the virological suppression, whereas one patient, who started with a peak HIV-RNA of 102.657 copies/mL, had a HIV-RNA determination of 55 copies/mL. The seven patients who reached 24 weeks of follow-up had a HIV-RNA quantification <50 copies/mL; of them, five reached 48 weeks of follow-up and all of them had an undetectable viral load (Table 1).

Table 1.

Virological and Immunological Determinations in Detail

	Baseline, HIV-RNA (copies/mL)	Baseline, CD4+ cell count (cell/mm³)	8 Weeks, HIV-RNA (copies/mL)	8 Weeks, CD4+ cell count (cell/mm³)	24 Weeks, HIV-RNA (copies/mL)	24 Weeks, CD4+ cell count (cell/mm³)	48 Weeks, HIV-RNA (copies/mL)	48 Weeks, CD4+ cell count (cell/mm³)	Notes
Patient 1	73,451	356	<37	NA	UND	392	UND	420
Patient 2	94,033	299	48	NA	<37	345	UND	404
Patient 3	102,657	307	55	NA	<37	371	UND	439
Patient 4	38,975	201	<37	NA	UND	278	UND	388
Patient 5	66,003	413	<37	NA	UND	486	UND	532
Patient 6	34,571	421	<37	NA	UND	510
Patient 7	85,772	496	39	NA	UND	566
Patient 8	40,665	251	<37	353
Patient 9	114,866	328	<37	577
Patient 10	55,833	463							HIV-RNA at 3 weeks: 104 copies/mL

NA, not available; UND, undetectable.

During a cumulative observation time of 86.4 patient-months of follow-up, we did not observe any adverse event or treatment discontinuation in our cohort. Genotypic resistance testing was performed for all patients at baseline: nine of them had no resistance mutations, whereas one patient presented Y188C and D232N mutations that may result in resistances to non-nucleoside reverse transcriptase inhibitors drugs and to first-generation INSTI elvitegravir and raltegravir. Nonetheless, this patient resulted virologically suppressed after 8 weeks from treatment introduction, with a HIV-RNA quantification of 38 copies/mL.

These preliminary results are in line with the clinical trials regarding the efficacy of a first-line regimen with lamivudine and dolutegravir, and may prompt physicians to consider this strategy in selected patients.

To the best of our knowledge, these are the first data from clinical practice evaluating the efficacy and safety of a dual regimen of dolutegravir plus lamivudine in naive HIV-positive patients. Our results are limited by the small sample size and the short follow-up period; nonetheless, our study is another evidence that, even in a real-life scenario, dolutegravir plus lamivudine may be a safe and effective option for treatment-naive HIV-infected patients.

Footnotes

Author Disclosure Statement

A.B. reports grants from Bristol-Myers Squibb and Gilead Sciences, and nonfinancial support from Bristol-Myers Squibb, ViiV Healthcare and Janssen-Cilag. A.Ca. has received a personal grant from Abbott., Gilead and ViiV. 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 other authors disclose no conflicts of interest.

Funding Information

No funding was received for this article.

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