Search

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.

Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients., Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated., Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles., Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available., Competing Interests: JRS, AA, AO, and JP have received research funding, consultancy fees and lecture sponsorships from, and have served on advisory boards for Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare. JP and JS have received research funding and consultancy fees from, and have served on advisory boards for Gilead Sciences, Merck Sharp & Dohme and ViiV Healthcare. PD has received honoraria for speaking or participating in advisory boards and/or research grants from the following pharmaceutical companies: Glaxo SmithKline GSK, Abbvie, Boehringer-Ingelheim, Bristol-Myers Squibb, Jansen & Cilag, Merck & Dohme, Gilead Sciences, Pfizer Inc, Thera technologies, ViiV Healthcare, Roche, and Ferrer International. MM has received research funding, consultancy fees and lecture sponsorships from, and has served on advisory boards for Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare. MM-A has received consultancy fees and lecture sponsorships from and has served on advisory boards for Gilead Sciences, Janssen-Cilag, ViiV Healthcare and Merck Sharp & Dohme. JN has received fees for educational activities and/or consultancies and/or financial support for attending conferences from Abbvie, Gilead Science, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare out of the submitted work. MV has received research funding, consultancy fees and lecture sponsorships from, and has served on advisory boards for Gilead and ViiV Healthcare. AI has received research funding, consultancy fees, and lecture sponsorships from, or has served on advisory boards for Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, Thera Technologies and ViiV Healthcare. PB has received consultancy fees from, and has served on advisory boards for Gilead Sciences, Merck Sharp & Dohme, Janssen-Cilag and ViiV Healthcare. RP has received research funding and consultancy fees and/or has served on advisory boards for Boehringer-Ingelheim, Gilead Sciences, Glaxo Smith-Kline, Merck Sharp & Dohme, Pfizer, and ViiV Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Santos, Casadellà, Noguera-Julian, Micán-Rivera, Domingo, Antela, Portilla, Sanz, Montero-Alonso, Navarro, Masiá, Valcarce-Pardeiro, Ocampo, Pérez-Martínez, García-Vallecillos, Vivancos, Imaz, Iribarren, Hernández-Quero, Villar-García, Barrufet, Paredes and INSTINCT study group.)

Two-drug regimens (2DRs) are emerging in clinical practice guidelines as treatment option for both naive and treatment-experienced people living with HIV (PLHIV). Objectives: To determine the real-life effectiveness of 2DR with 25 mg RPV plus 50 mg DTG in a single-tablet regimen (RPV/DTG STR ) and its impact on viral and immune status, lipid profile, and inflammatory markers. Methods: This observational study included 291 treatment-experienced PLHIV, starting 2DR with RPV/DTG STR between 29 January 2019 and 2 February 2022, who were followed up for at least six months. Participants gave verbal informed consent for the switch in antiretroviral therapy (ART) to RPV/DTG STR . Results: The mean age of the 291 participants was 51.3 years; 77.7% were male; and 42.9% were in the AIDS stage with a CD4 nadir of 283.5 ± 204.6 cells/uL. The median time since HIV diagnosis was 19.7 years (IQR: 10.6-27). Before 2DR, patients received a median of five ART lines (IQR: 3-7) for 22.2 years (IQR: 14-26), with 34.4% ( n = 100) receiving a three-drug regimen (3DR), 31.3% ( n = 91) receiving monotherapy, and 34.4% ( n = 100) receiving 2DR. The median time on RPV/DTG STR was 14 months (IQR: 9.5-21); 1.4% were lost to the follow-up. Effectiveness was 96.2% by intention-to-treat (ITT) analysis, 97.5% by modified ITT, and 99.3% by per-protocol analysis. Virological failure was observed in 0.69%, blips in 3.5%, and switch to another ART in 1.4%. The mean lipid profile improved, with reductions in TC/HDLc ratio (3.9 ± 0.9 vs. 3.6 ± 0.9; p = 0.0001), LDLc (118.3 ± 32.2 mg/dL vs. 106.2 ± 29.8 mg/dL, p = 0.0001), TG (130.9 ± 73.9 mg/dL vs. 115.9 ± 68.5 mg/dL, p = 0.0001), and CD4/CD8 ratio increase (0.99 ± 0.58 vs. 1.01 ± 0.54; p = 0.0001). The cost-effectiveness of 2DR with RPV/DTG STR was similar to that of DTG/3TC and superior to those of BIC/TAF/FTC and DRV/c/TAF/FTC, with higher virological suppression and lower annual costs. Conclusions: The switch to RPV plus DTG in STR is a cost-effective, long-lasting, and robust strategy for PLHIV, with a very long experience of treatment, which improves the lipid profile without affecting inflammatory markers.

The current morbimortality of serious infections is unacceptable and there is a need to promote the increase in the efficacy of empirical and targeted antibiotherapy. This could be achieved by initiatives coming from ASP teams aimed at promoting increased efficacy of antibiotic therapy .In the optimization of the antibiotic therapy there are several critical points in which an adequate timing could achieve benefits in the survival of patients with severe infections: prompt initiation of empirical treatment; de-escalation performance, appropriate targeted treatment; and finally, curtail antibiotic duration., (©The Author 2022. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)