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Objectives We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine. Methods We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. Results We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P  = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P  = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P  = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P  = 0.014). Conclusions Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of dolutegravir plus lamivudine dual therapy (DT) with that of dolutegravir plus two NRTIs triple therapy (TT) as switch strategies.Methods: A multicentre cohort of HIV-positive, HBsAg-negative patients with viral suppression (HIV-RNA ≤50 copies/mL) switching to DT or TT was retrospectively selected from the ARCA database. The effect of DT versus TT on virological failure (VF; defined as two consecutive HIV-RNA values >50 copies/mL or one HIV-RNA value ≥200 copies/mL) was evaluated by multivariable Cox regression models, overall and after stratifying for the presence of NRTI resistance-associated mutations (RAMs).Results: From December 2014 to June 2020, 628 patients were eligible: 118 (18.8%) started tenofovir/emtricitabine/dolutegravir, 306 (48.7%) abacavir/lamivudine/dolutegravir and 204 (32.5%) lamivudine/dolutegravir. The DT group had significantly higher nadir and baseline CD4 counts, a higher duration of viral suppression and a lower prevalence of RAMs at historical genotype. Overall, 41 VF occurred after a median of 1.7 years of follow-up, with a lower, but not statistically significant, rate for DT [versus TT, adjusted HR (aHR) = 0.58, 95% CI = 0.25-1.34]. However, DT was associated with less VF in the absence of RAMs when compared with tenofovir-based TT (aHR = 0.20, 95% CI = 0.06-0.67), but not with abacavir-based TT (aHR = 0.43, 95% CI = 0.17-1.11). Conversely, in the setting of pre-existing M184V/I, DT showed a trend to increased risk of VF (versus tenofovir-based TT, aHR = 137.50, 95% CI = 4.24-4464.06; versus abacavir-based TT, aHR = 33.88, 95% CI = 1.75-656.47).Conclusions: Lamivudine/dolutegravir maintenance DT showed similar efficacy to dolutegravir-based TT; however, past M184V/I may favour VF. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs.Methods: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for SLC22A2 808 C → A polymorphism and dolutegravir Ctrough. The Symptom Checklist-90-R [investigating 10 psychiatric dimensions and reporting a general severity index (GSI)], a self-reported questionnaire and the Mini-International Neuropsychiatric Interview were offered to investigate current NPs. The effects of dolutegravir Ctrough and the SLC22A2 gene variant on NPs were explored by multivariable logistic regression.Results: A cohort of 203 patients was analysed: 71.4% were male, with median age 51 years and 11 years of ART exposure. Median time on dolutegravir was 18 months. Dolutegravir was associated with different antiretroviral combinations (mainly lamivudine, 38.9%, and abacavir/lamivudine, 35.5%). SLC22A2 CA genotype was independently associated with an abnormal GSI [adjusted OR (aOR) 2.43; P = 0.072], anxiety (aOR 2.61; P = 0.044), hostility (aOR 3.76; P = 0.012) and with moderate to severe headache (aOR 5.55; P = 0.037), and dolutegravir Ctrough was associated with hostility (fourth versus first quartile aOR 6.70; P = 0.007) and psychoticism (fourth versus first quartile aOR 19.01; P = 0.008). Other NPs were not associated with SLC22A2 polymorphism or dolutegravir Ctrough.Conclusions: A variant of the OCT2-encoding gene, in addition to or in synergy with higher dolutegravir Ctrough, is associated with a set of NPs observed during dolutegravir therapy. [ABSTRACT FROM AUTHOR]

Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups.Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models.Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI -1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had <50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI -2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT.Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI. [ABSTRACT FROM AUTHOR]