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Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.

Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population-based, prospective, multicentre cohort study was carried out. Treatment-naive subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. Results A total of 4165 subjects (37% treatment-naive) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

Objective The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study. Methods This was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay. Total cholesterol (total-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined using standard methods. Results Fifty-four patients were included in the study [34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm]. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P?=?0.026), and MCP-1, which was higher in the TC arm (P?=?0.039). MCP-1 and sVCAM-1 were increased relative to baseline at the three study time-points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P?=?0.02). t-PA was increased in both arms at the three time-points. Total-c, HDL-c and low-density lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time-points, with no changes in the total-c/HDL-c ratio. HIV viral load positively correlated with MCP-1 at months 12 and 24. Regression analysis showed a significant negative association of HDL-c with MCP-1 and sVCAM-1. Conclusions A significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.

Objective The aim of the study was to evaluate the efficacy of fosamprenavir/ritonavir (FPV/r) monotherapy in plasma and reservoirs in virologically suppressed patients. Methods A 48-week, prospective, single-arm pilot trial was carried out (trial registration: ISRCTN78584791). Patients receiving triple therapy [FPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) for at least the previous month], with viral load (VL) 40 copies/mL in three consecutive samples or >500 copies/mL in two samples. Results Enrolment was prematurely stopped because of a high percentage of VF. Twenty patients (45% men; median age 43.5 years) were included in the trial. Nine patients (45%) presented therapeutic failure [seven (35%) had VF, and two discontinued therapy]. Resistance testing was available in five patients. One patient presented major PI mutations (54L, 32I and 47V) in addition to one minor mutation (13V), whereas two patients had minor PI mutations (10V + 136I and 71T, respectively). The patient with major PI mutations switched from FPV/r to darunavir/r and VL was re-suppressed. In the other six patients with VF, VL was re-suppressed after the reintroduction of NRTIs. VL was