Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other ...nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce.
Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50 copies/ml was analyzed at 48 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs.
Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9 years, respectively. At baseline, viral load was less than 50 copies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50 copies/ml 82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively ( P = 0.2). In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50 copies/ml 94.4% (359/380) vs. 93.8% (61/65); P = 0.2. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died).
Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination.
To evaluate the in vivo relevance of the inhibitory effect of tenofovir on telomerase activity observed in vitro.
Cross-sectional study of HIV-infected patients with suppressed virological ...replication (HIV RNA <50 copies/mL for more than 1 year).
Telomere length in whole blood was measured by quantitative real-time polymerase chain reaction. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders.
200 patients included, 72% men, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing antiretroviral treatment (ART) regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis, significant predictors of shorter telomere length were older age (P = 0.008), parental age at birth (P = 0.038), white race (P = 0.048), and longer time of known HIV infection (10-20 and ≥20 years compared with <10 years, P = 0.003 and P = 0.056, respectively). There was no association between TDF exposure and telomere length after adjusting for possible confounding factors (age, parental age at birth, race, and time of HIV infection). Total time receiving ART and duration of treatment with nucleoside reverse transcriptase inhibitors were associated with shorter telomere length, but these associations were explained by time of known HIV infection.
Our data do not suggest that telomerase activity inhibition caused by TDF in vitro leads to telomere shortening in peripheral blood of HIV-infected patients.
Rat hepatitis E virus (ratHEV; species
) is considered a newly emerging cause of acute hepatitis of zoonotic origin. ratHEV infection of people living with HIV (PLWH) might portend a worse, as with ...hepatitis E virus (HEV; species
), and consequently this group may constitute a high-risk population. We aimed to evaluate the prevalence of ratHEV by measuring viral RNA and specific IgG antibodies in a large Spanish cohort of PLWH. Multicentre study conducted in Spain evaluating PLWHIV included in the Spanish AIDS Research Network (CoRIS). Patients were evaluated for ratHEV infection using PCR at baseline and anti-ratHEV IgG by dot blot analysis to evaluate exposure to ratHEV strains. Patients with detectable ratHEV RNA were followed-up to evaluate persistence of viremia and IgG seroconversion. Eight-hundred and forty-two individuals were tested. A total of 9 individuals showed specific IgG antibodies against ratHEV, supposing a prevalence of 1.1 (95% CI; 0.5%-2.1%). Of these, only one was reactive to HEV IgG antibodies by ELISA. One sample was positive for ratHEV RNA (prevalence of infection: 0.1%; 95% CI: 0.08%-0.7%). The case was a man who had sex with men exhibiting a slightly increased alanine transaminase level (49 IU/L) as only biochemical alteration. In the follow-up, the patients showed undetectable ratHEV RNA and seroconversion to specific ratHEV IgG antibodies. Our study shows that ratHEV is geographical broadly distributed in Spain, representing a potential zoonotic threat.
Background. The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. Methods. We prospectively included ...aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. Results. Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was −0.04 (95% confidence interval, −.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, −0.09 95% confidence interval, −.16 to −.01 vs −0.08 −.14 to −.02, after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 22.2%; triple therapy, 4 of 19 21.1%; P = .91) and vice versa (monotherapy, 5 of 44 10.2% and triple therapy, 3 of 45 6.3%; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. Conclusions. The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.
Objective
To analyze the results of cardiac valve replacement in a multicenter cohort of patients with antiphospholipid syndrome (APS) and to identify prognostic factors of poor outcome.
Methods
We ...performed a retrospective analysis of clinical manifestations (cardiac involvement and APS characteristics), operative and early postoperative courses, and long‐term followup. All of the patients fulfilled the Sapporo criteria for APS. Logistic regression analyses were performed to identify those variables associated with adverse outcomes.
Results
Between 1981 and 2008, 33 valvular replacements were carried out in 32 patients with APS. The mean ± SD age at the time of surgery was 43.09 ± 14.08 years. Thirty patients were women. Primary APS was present in 21 patients. The median followup time after surgery was 33.5 months (range 0–192 months). The mitral valve was the most frequently replaced (22 of 33). Mechanical valve replacement was performed in 23 patients (71.9%). The mortality rate was 12.5% (1 cardiogenic shock, 1 septic shock, 1 following renal transplantation, and 1 hemorrhagic stroke). Fourteen patients experienced 20 complications (8 major bleeding, 5 thrombotic events, 2 valvular deteriorations, 2 third‐degree atrioventricular block, 1 endocarditis, 1 cardiac tamponade, and 1 cardiac failure). Fifty percent of the patients had an uneventful outcome.
Conclusion
Morbidity and mortality were high in APS patients undergoing valve replacement surgery. Most complications were related to thrombosis and bleeding. Anticoagulation must be carefully monitored to prevent hemorrhagic and thrombotic complications.
In vitro, tenofovir and abacavir induced a significant dose-dependent inhibition of telomerase activity at therapeutic concentrations in peripheral blood mononuclear cells of healthy subjects. Median ...inhibition of telomerase activity by tenofovir at 0.5 and 1 μM was 29% Interquartile range (IQR) 29%-34%, P = 0.042 and 28% (IQR 28%-41%, P = 0.042), respectively. Abacavir inhibition was 12% (IQR 9%-13%, P = 0.043) at 3 μM and 14% (IQR 10%-29%, P = 0.043) at 10 μM. Tenofovir and abacavir did not change human telomerase reverse transcriptase (hTERT) levels or mRNA levels of other telomerase complex genes. Exposure to emtricitabine or darunavir did not affect telomerase activity, hTERT protein levels, or mRNA levels of telomerase/shelterin genes.
Abstract
Background
Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon ...evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality.
Methods
This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives.
Results
We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS.
Conclusions
In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.
This trial explores the subclinical neurotoxicity of DTG/3TC/ABC and its reversibility after switching to DRV/COBI/FTC/TAF in virologically suppressed HIV-infected individuals, a regimen known for its safety neuropsychiatric profile. Results will help to understand the neurotoxicity profile of dolutegravir-based therapies.
In a cross-sectional study of aviremic neurocognitively impaired patients receiving protease inhibitors as triple-drug therapy (n = 30) or as monotherapy (n = 22), we found no statistically ...significant differences in the types of cognitive domains involved or severity of cognitive deficit. Cerebrospinal fluid concentrations of total proteins, total tau, myelin basic protein, neuron-specific enolase, β2 microglobulin, S100B protein, or prevalence of cerebrospinal fluid HIV-RNA detection by standard (6.3% vs 7.1% P = 1) or ultrasensitive assays (50% vs 71.4%, P = 0.28) were similar in both groups. These results do not suggest important differences in the pattern of neurocognitive impairment between groups receiving very different antiretroviral strategies.
Objectives Data are scarce on the long-term efficacy of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression. Four years of results of patients randomized to monotherapy in the Only ...Kaletra (OK) pilot clinical trial are presented. Patients and methods Twenty-one HIV-infected patients with suppressed HIV replication (<50 copies/mL) for at least 6 months and without previous failure while receiving a protease inhibitor-based regimen started lopinavir/ritonavir monotherapy. Follow-up was performed within the OK pilot clinical trial during the first 2 years and according to routine clinical practice during the 3rd and 4th years. Results Fourteen patients (67%) remain on monotherapy and with RNA <50 copies/mL (intention-to-treat analysis, with missing patients scored as failures). Five patients (24%) had virological rebound and all of them were successfully re-suppressed by adding two nucleosides. No major protease inhibitor mutations were found. Conclusions Our data support the long-term efficacy and safety of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression, a finding that must be confirmed in larger studies.
Risk factors for loss of virological response in patients receiving lopinavir/ritonavir (LPV/r) monotherapy as maintenance treatment have not been determined.
In 121 patients enrolled in the OK and ...OK04 clinical trials assigned to receive monotherapy with LPV/r, we attempted to identify factors associated with loss of virological suppression at 48 weeks, defined as confirmed serum HIV type-1 RNA>50 copies/ml, with missing data or changes caused by toxicity censored. Univariate and multivariate Cox proportional hazard models were used to calculate hazard ratios for the risk of loss of virological suppression.
At week 48, 15 patients experienced loss of virological suppression. Probability of loss of virological suppression was 12.7%. Less than 9 months of maintenance of virological suppression prior to monotherapy, a lower baseline haemoglobin and low adherence measured by self-reported total missed doses in the week prior to study visit were associated with loss of virological suppression in the univariate analyses. Independent factors associated with loss of virological suppression by multivariate analyses were > or =2 visits with self-reported missed doses in the week prior to the study visit, a lower baseline haemoglobin and a nadir CD4(+) T-cell count <100 cells/microl.
Suboptimal adherence, lower baseline haemoglobin and a nadir CD4(+) T-cell count <100 cells/microl were the main risk factors for losing virological suppression in patients randomized to monotherapy with LPV/r.
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