Real world effectiveness of standard of care triple therapy versus two-drug combinations for treatment of people living with HIV

Abstract

Background Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients. Methods A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA<50 copies/mL at baseline, irrespective of the regimen used. The following endpoints were assessed: time to discontinuation for any reason, time to switch due to virologic failure, and time to switch due to toxicity (reasons for discontinuation according to clinician report in the database). Time-to-event analyses were conducted using Kaplan–Meier survival curves and Cox regression models. Results Overall 7,481 patients were included in the analysis, contributing to 9,243 patient-regimens. Patient characteristics at baseline differed among groups, with the 2DC group being significantly older and having a higher proportion of women, a longer time on ART and a higher number of previous virologic failures. Median (95% Confidence Interval [C.I.]) time to switch was 2.5 years (2.3, 2.7) in 2DC group versus 2.9 years (2.7, 3.0) in TT. Adjusted hazard ratios (95% C.I.) for discontinuation due to any reason, virologic failure and toxicity in the 2DC vs TT group were 1.29 (1.15; 1.44), 2.06 (1.54; 2.77) and 1.18 (0.94; 1.48), respectively. Results were consistent in the two sub-analyses. Conclusion In this analysis, time to discontinuation and probability of remaining free of virologic failure were significantly higher in patients on INSTI-based TT compared to DTG- and/or bPI-containing 2DC, with no differences in toxicity.

Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos

“…At present, DTG-containing regimens account for 40-50% of the antiretroviral therapy of patients with HIV infection [2], since DTG is considered one of the safest antiretroviral drugs against HIV. However, reports from clinical practice about the high rate of neuropsychiatric adverse events (including sleep disorders, depression, anxiety, and suicidal behaviors) in patients treated with DTG that can lead to treatment discontinuation have raised questions on the tolerability of DTG-based regimens [1,3].…”

Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centred approach. Consensus Guidance Using a Delphi Process

“…Moreover, new ART strategies with new drugs have been recently introduced in clinical practice and are becoming widely used worldwide [3][4][5][6][7][8], outlining a scenario where therapies can be increasingly tailored to combine efficacy and tolerability with long-term durability [1,2,9]. The new drug class of integrase inhibitors (INSTIs) has allowed to expand strategies for initiating and simplifying antiretroviral therapy (ART) [3,4,8], but literature data, mainly derived from the clinical practice, highlight how INSTIs cannot yet be considered therapies for every patient [10][11][12][13][14]. Indeed, clinical and virological characteristics of each single subject should be considered before choosing drugs either for ART-naïve or -experienced PLWH.…”