Objectives
Despite the importance of neuropsychiatric comorbidities (NPCs) in people with HIV, the degree of physician compliance with recommendations for diagnosis and management is unknown. This ...study assessed the perceptions, knowledge, skills, and attitudes of physicians regarding the diagnosis and management of NPCs in people with HIV in hospital settings in Spain.
Methods
This was a cross‐sectional study including non‐psychiatrist HIV specialist physicians responsible for antiretroviral therapy (ART) prescription and clinical care of ≥50 people with HIV/month, who completed an online survey of 34 questions.
Results
The 115 physicians who completed the survey (totally) agreed that assessing mental health was relevant (97.4%) and that NPCs were underdiagnosed (76.6%) and were very/fairly sensitized (67.8%). However, they reported receiving little/no training on the detection of NPCs (64.3%). Physicians considered that patients underreported NPCs (53.9%) and that alcohol (94.8%), recreational substances (97.4%), and tobacco consumption (95.6%) were (very) relevant. Physicians agreed that NPCs were difficult to identify (52.2%) and that few tools were available (53.0%) and failed to use questionnaires (79.1%) and follow guidelines (77.4%) for the detection of NPCs. The main reasons precluding appropriate diagnosis and evaluation were lack of proactive attitudes and specific training and limited visit time. Upon detection of NPCs, physicians referred patients to the in‐house psychiatry/psychology centre (61.7%), adjusted ART to minimize interactions (96.5%), and managed NPCs in conjunction with mental health professionals (71.3%).
Conclusions
Physicians in hospital settings in Spain were aware of the relevance of NPC diagnosis and their underdiagnosis. However, they still failed to routinely evaluate NPCs, follow guideline recommendations, and use questionnaires, highlighting opportunities for improved NPC detection and management in people with HIV.
Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown.
A prospective cohort of human immunodeficiency virus (HIV)-infected participants with ...suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF.
A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides of whom 69 were receiving abacavir, 25 were receiving a nucleostide reverse transcriptase inhibitor N{t}RTI-sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside.
In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.
Background & objective
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people living with HIV (PLWH) and the expression of some microRNAs could be useful as biomarkers for the ...diagnosis of NAFLD. The aim of this study was to identify patterns of differential expression of microRNAs in PLWH and assess their diagnostic value for NALFD.
Methods
A discovery case-control study with PLWH was carried out. The expression of miRNAs was determined using HTG EdgeSeq technology. Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, BMI, CD4+ lymphocyte count, active HCV infection, and ART regimen.
Results
Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study.
Conclusion
Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.
Persons with substance use disorder are at increased risk for hepatitis B virus (HBV) infection. Although most of them are attached to social health centers, the vaccination rate in this group is ...low. In this context, we designed a study to evaluate the prevalence of users of drug addiction centers (DAC) not immunized against hepatitis B and to compare the rate of vaccination against hepatitis B with the rate of immunization against SARS-Cov-2 in 2 years of follow-up.
Retrospective study that included individuals attended at DAC. Patients were screened at baseline (June 2020-January 2021) for HBV immunization. Individuals with HBsAb < 10 IU/mL were recommended to receive hepatitis B vaccine, during follow-up (January 2021-October 2022). At the end of follow-up, the HBV vaccination rate among candidates was determined and compared with the vaccination rate against SARS-Cov-2 in this population in the same period.
A total of 325 subjects were surveyed and tested. At baseline, the 65% (211/325) of were candidates to initiate vaccination and were advisor to HBV vaccination. During the follow-up 15 individuals received at least one dose of HBV vaccine, supposing a vaccination rate of 7.2%. In the same period, 186 individuals received at least one dose against SARS-Cov-2, representing a vaccination rate of 83%. The comparison between vaccination rates reached statistically significant (
< 0.001).
Our study manifests a low rate of immunization against HBV in DAC users, despite a high level of immunization for SARS-Cov-2 during the same period in the same population. Consequently, the lack of immunization against HVB in this population might be related with health policy issue more than to individuals linked to care and awareness. A similar approach for vaccination intended for SARS-CoV2 should be applied in high-risk population to warrant the success of immunization program against other preventable diseases such as HBV.
The burden hepatitis C infection in people with history or current drug use suppose a high risk of hepatic complications and transmission infectious disease. This population is poor linked to heath ...system and is difficult to achieve them and support treatment because they have high rates of lost follow-up. Our aim was to evaluate an intervention for the diagnosis and treatment of chronic hepatitis C and HIV in this population.
Six-hundred and eighty-three people attended in Drugs and Addictions Centers (DAC) were asked to participate in health counseling and provide blood sample for test HCV, HIV, and syphilis from April 2019 to June 2020. Totally 556 subjects were surveyed and tested. All of them were assigned to a patient navigation program to improve health education and linking to the sanitary system. Hepatitis C infection patients were evaluated in an ampliated medical consult to evaluate hepatic stage with transient liver elastography and initiated Direct Acting Antivirals to achieve Sustained Viral Response.
Of the 556 patients who agreed to participate in the study, 33 (5.9%) had active HCV infection. Of the 33 patients infected with HCV, three were lost to follow-up once the diagnosis of HCV infection was made. Twenty-eight patients (93.3%) completed treatment and 26 achieved Sustained Viral Response (78.8%). Of the 30 patients, seven (23.3%) had advanced fibrosis, and of these, four (16.6%) had liver cirrhosis. One of the cirrhotic patients had hepatic space-occupying lesions at the baseline evaluation and was diagnosed with hepatocarcinoma.
Our study suggests that the implementation of strategies based on personalized intervention models can contribute to the control of HCV infection in DAC users.
In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease ...inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.
In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.
Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15).
Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.
Tenofovir alafenamide is a prodrug that reduces tenofovir plasma concentrations by 90% compared with tenofovir disoproxil fumarate, thereby decreasing bone and renal risks. The coformulation of ...rilpivirine, emtricitabine, and tenofovir alafenamide has recently been approved, and we aimed to investigate the efficacy, safety, and tolerability of switching to this regimen compared with remaining on coformulated efavirenz, emtricitabine, and tenofovir disoproxil fumarate.
In this randomised, double-blind, placebo-controlled, non-inferiority trial, HIV-1-infected adults were enrolled at 120 hospitals and outpatient clinics in eight countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA <50 copies per mL) on efavirenz, emtricitabine, and tenofovir disoproxil fumarate for at least 6 months before enrolment and had creatinine clearance of at least 50 mL/min. Participants were randomly assigned (1:1) to receive a single-tablet regimen of rilpivirine (25 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) or to continue a single-tablet regimen of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), with matching placebo. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (assessed by the US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 8%. This study was registered with ClinicalTrials.gov, number NCT02345226.
Between Jan 26, 2015, and Aug 27, 2015, 875 participants were randomly assigned and treated (438 with rilpivirine, emtricitabine, and tenofovir alafenamide and 437 with efavirenz, emtricitabine, tenofovir disoproxil fumarate). Viral suppression at week 48 was maintained in 394 (90%) of 438 participants assigned to the tenofovir alafenamide regimen and 402 (92%) of 437 assigned to the tenofovir disoproxil fumarate regimen (difference -2·0%, 95·001% CI -5·9 to 1·8), demonstrating non-inferiority. 56 (13%) of 438 in participants in the rilpivirine, emtricitabine, and tenofovir alafenamide group experienced treatment-related adverse events compared with 45 (10%) of 437 in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group.
Switching to rilpivirine, emtricitabine, and tenofovir alafenamide from efavirenz, emtricitabine, and tenofovir disoproxil fumarate was non-inferior in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection.
Gilead Sciences.
Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living with HIV (PLHIV). However, their ...use has been associated with neuropsychiatric symptoms (NPSs) that may lead to treatment discontinuation. We aim to describe and synthesize information on safety and discontinuation rates and to summarize potential risk factors associated with the development of NPSs in PLHIV treated with these regimens.
A systematic review of the literature was carried out in the international databases PubMed/Medline, Web of Science (WoS), Scopus, Embase, and Cochrane Library from 2013 to June 2022. Ninety observational studies reporting data on treatment discontinuation due to drug-related adverse events and NPSs were identified.
Discontinuation rates due to NPSs increase with treatment time and, in light of the reviewed studies, are higher in PLHIV treated with DTG-based regimens compared with those treated with BIC/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF). This information could be useful for clinicians during treatment decision-making, reducing discontinuation rates and thereby promoting treatment success and durability. Additionally, the identification of potential risk factors in PLHIV prior to starting therapy could also help make the best therapy choices based on the characteristics of each individual.
Introduction
Penetration of protease inhibitors (PI) in the central nervous system (CNS) is limited. Therefore, there are concerns about the capacity of PI monotherapy (MT) to control HIV in CNS and ...preserve brain integrity.
Methods
Exploratory case‐control study designed to compare neuronal integrity and brain inflammation in HIV‐suppressed patients (>2 years) with and without neurocognitive impairment (NI), treated with MT or triple therapy (TT), 3‐Tesla cerebral magnetic resonance image (MRI) and spectroscopy (MRS) were used to evaluate neuronal integrity (volume of cerebral structures and MRS levels of N‐acetyl‐aspartate (NAA)) and brain inflammation (MRS levels of myo‐inositol (MI) and choline (CHO)). MRS biomarkers were measured in 4 voxels located in basal ganglia, frontal (2) and parietal lobes. A comprehensive battery of tests (14 tests ‐ 7 domains) was used to diagnose neurocognitive impairment 1.
Results
We included 18 neurocognitively impaired patients (MT: 10, TT: 8) and 21 without NI (MT: 9; TT: 12, Table 1). Subset of patients with NI: cerebral volumes and MRS biomarkers were mostly similar between MT and TT with exception of the right cingulate nucleolus volume (MT: 8854±1851 vs TT: 10482±1107 mm3; p<0.04), CHO levels in basal ganglia (MT: 0.44±0.05 vs TT: 0.37±0.03 MMOL/L; p<0.01) and the NAA levels in parietal lobe (MT: 1.49±0.12 vs 1.70±0.13 MMOL/L; p<0.01). Subset of patients without NI: cerebral volumes and MRS biomarkers were mostly similar between MT and TT with exception of MI levels in frontal lobe (MT: 1.20±0.36 vs 0.81±0.25 MMOL/L; p=0.01).
Conclusions
We did not find significant differences in cerebral volumes or MRS biomarkers in most areas of the brain. However, we found higher levels of inflammation and neuronal damage in some brain areas of patients who received MT. This observation has to be taken into caution while we could not adjust our results by potential confounders. Further investigation is needed to confirm these preliminary results.
Introduction
Due to their low CNS penetrance, there are concerns about the capacity of non‐conventional PI‐based ART (monotherapy and dual therapies) to preserve neurocognitive performance (NP).
...Methods
We evaluated the NP change of aviremic participants of the SALT clinical trial 1 switching therapy to dual therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform an NP assessment (NPZ‐5) at baseline and W48. Neurocognitive impairment and NP were assessed using AAN‐2007 criteria 2 and global deficit scores (GDS) 3. Neurocognitive change (GDS change: W48 – baseline) and the effect of DT on NP evolution crude and adjusted by significant confounders were determined using ANCOVA.
Results
A total of 158 patients were included (Table 1). They had shorter times because HIV diagnosis, ART initiation and HIV‐suppression and their virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared to the 128 patients not included in the sub‐study. By AAN‐2007 criteria, 51 patients in each ART group (68% vs 63%) were neurocognitively impaired at baseline (p=0.61). Forty‐seven patients were not reassessed at W48: 30 lost of follow‐up (16 DT‐14 TT) and 17 had non‐evaluable data (6 DT‐11 TT). Patients retested were more likely to be men (78.9% vs 61.4%) and had neurological cofounders (9.6% vs 0%) than patients non‐retested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of 21 (10.5%) on TT who were non‐impaired at baseline became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%) on TT who were neurocognitively impaired at baseline became non‐impaired (p=0.44). Mean GDS changes (95% CI) were: Overall −0.2 (−0.3 to −0.04): DT −0.26 (−0.4 to −0.07) and TT −0.08 (−0.2 to 0.07). NP was similar between DT and TT (0.15). This absence of differences was also observed in all cognitive tests. Effect of DT: −0.16 −0.38 to 0.06) (r2=0.16) on NP evolution was similar to TT (reference), even after adjusting (DT: −0.11 −0.33 to 0.1, TT: reference) by significant confounders (geographical origin, previous ATV use and CD4 cell count) (r2=0.25).
Conclusions
NP stability was observed after 48 weeks of follow up in the majority of patients whether DT or TT was used to maintain HIV‐suppression. Incidence rates of NP impairment or NP impairment recovery were also similar between DT and TT.
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