This was a retrospective study on the efficacy and drug resistance mutations selected at virological failure (VF) in prospectively-followed HIV-infected patients switched to dolutegravir plus rilpivirine (DTG+RPV) or lamivudine (DTG+3TC) while virologically suppressed (HIV-RNA <50 copies/mL). VF was defined as HIV-RNA >50 copies/mL in two consecutive determinations or in a single determination if followed by treatment modification, or >1000 copies/mL in a single determination. Totally, 374 patients were analysed (307 switched to DTG+3TC and 67 to DTG+RPV); 220 had documented historical resistance. The median (IQR) time with HIV-RNA <50 copies/mL before switch was 4.52 (1.93–8.14) years. VF occurred in 17 patients after a median of 1.74 (0.90–2.46) years of follow-up in the 3TC group [incidence rate (95% CI) 3.34 (2.08–5.37) per 100-PYFU] and in 2 patients after a median of 1.78 (1.10–2.99) years of follow-up in the RPV group [incidence rate (95% CI) 1.57 (0.4–6.28) per 100-PYFU]. The 48-week estimated probabilities to maintain virological suppression during treatment with a two-drug regimen were 97.8% (95% CI 95.1–99.0%) vs. 98.3% (95% CI 88.6–99.8%) in the 3TC versus RPV group (P = 0.311). At switch, patients with VF had undetectable HIV-RNA since 0.71 (0.23–1.07) years versus 1.49 (0.64–2.2) years in those without VF (P = 0.001). In the 3TC group, VF was not associated with the presence of historical resistance to nucleoside analogues, and DTG-resistant variants were not selected at VF. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. VF was infrequent with these regimens and was negatively associated with duration of viral undetectability. Drug resistance mutations selected at failure of these regimens were those expected in case of failure of any regimen including DTG, 3TC or RPV, but the impact of resistance to NRTIs on efficacy of DTG+3TC seems lower than expected.

Retrospective study on the outcome of two-drug regimens based on dolutegravir plus one reverse transcriptase inhibitor in virologically-suppressed HIV-infected patients / Galizzi, N.; Poli, A.; Galli, L.; Muccini, C.; Mastrangelo, A.; Dell'Acqua, R.; Maillard, M.; Bossolasco, S.; Cinque, P.; Lazzarin, A.; Castagna, A.; Gianotti, N.. - In: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS. - ISSN 0924-8579. - 55:3(2020), p. 105893. [Epub ahead of print] [10.1016/j.ijantimicag.2020.105893]

Retrospective study on the outcome of two-drug regimens based on dolutegravir plus one reverse transcriptase inhibitor in virologically-suppressed HIV-infected patients

Muccini C.;Mastrangelo A.;Lazzarin A.;Castagna A.;
2020-01-01

Abstract

This was a retrospective study on the efficacy and drug resistance mutations selected at virological failure (VF) in prospectively-followed HIV-infected patients switched to dolutegravir plus rilpivirine (DTG+RPV) or lamivudine (DTG+3TC) while virologically suppressed (HIV-RNA <50 copies/mL). VF was defined as HIV-RNA >50 copies/mL in two consecutive determinations or in a single determination if followed by treatment modification, or >1000 copies/mL in a single determination. Totally, 374 patients were analysed (307 switched to DTG+3TC and 67 to DTG+RPV); 220 had documented historical resistance. The median (IQR) time with HIV-RNA <50 copies/mL before switch was 4.52 (1.93–8.14) years. VF occurred in 17 patients after a median of 1.74 (0.90–2.46) years of follow-up in the 3TC group [incidence rate (95% CI) 3.34 (2.08–5.37) per 100-PYFU] and in 2 patients after a median of 1.78 (1.10–2.99) years of follow-up in the RPV group [incidence rate (95% CI) 1.57 (0.4–6.28) per 100-PYFU]. The 48-week estimated probabilities to maintain virological suppression during treatment with a two-drug regimen were 97.8% (95% CI 95.1–99.0%) vs. 98.3% (95% CI 88.6–99.8%) in the 3TC versus RPV group (P = 0.311). At switch, patients with VF had undetectable HIV-RNA since 0.71 (0.23–1.07) years versus 1.49 (0.64–2.2) years in those without VF (P = 0.001). In the 3TC group, VF was not associated with the presence of historical resistance to nucleoside analogues, and DTG-resistant variants were not selected at VF. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. VF was infrequent with these regimens and was negatively associated with duration of viral undetectability. Drug resistance mutations selected at failure of these regimens were those expected in case of failure of any regimen including DTG, 3TC or RPV, but the impact of resistance to NRTIs on efficacy of DTG+3TC seems lower than expected.
2020
Dolutegravir
HIV
Integrase strand transfer inhibitor
Lamivudine
Rilpivirine
Two-drug regimen
Anti-HIV Agents
Drug Resistance, Viral
HIV Infections
Heterocyclic Compounds, 3-Ring
Humans
Lamivudine
Oxazines
Piperazines
Pyridones
Retrospective Studies
Reverse Transcriptase Inhibitors
Rilpivirine
Treatment Outcome
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/107456
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