Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters.

OBJECTIVES: The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. METHODS: The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. RESULTS: We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG + TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). CONCLUSION: Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.

Rat hepatitis E virus (Rocahepevirus ratti) in people living with HIV.

Rat hepatitis E virus (ratHEV; species Rocahepevirus ratti) 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 Paslahepevirus balayani), 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.

Lack of associations of microRNAs with severe NAFLD in people living with HIV: discovery case-control study.

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.

Brief transdiagnostic group intervention for people living with HIV and emotional disorders: feasibility and clinical utility.

Emotional regulation-based transdiagnostic interventions provide positive but limited evidence regarding efficacy with people living with human immunodeficiency virus (HIV). In the present study, 10 participants living with HIV with emotional disorders completed a five-session transdiagnostic group intervention to improve their emotional regulation skills (Unified Protocol). Changes at pre-treatment, post-treatment and three-month follow-up were explored at the population (mean-rank) and the individual level (reliable change index). Compared to pre-treatment, participants improved significantly in anxiety, depression, negative affect and quality of life. Changes were maintained at the three-month follow-up. Emotion regulation, particularly the confusion factor, improved when comparing pre-treatment with the three-month follow-up. At the three-month follow-up, the percentage of normalized scores was the largest in maladjustment (70%), followed by depression, negative affect, and lack of control (50%). All participants indicated high treatment satisfaction and perceived benefits. These promising results suggest that brief emotion regulation interventions might be feasible and effective in the public health settings for people living with HIV suffering emotional disorders.

Real-world discontinuations due to neuropsychiatric symptoms in people living with HIV treated with second-generation integrase inhibitors: a systematic review.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

Efficacy of a comprehensive strategy for the detection and treatment of hepatitis C infection in a population attending addiction centers.

Background and aims: 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. Methods: 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. Results: 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. Conclusions: Our study suggests that the implementation of strategies based on personalized intervention models can contribute to the control of HCV infection in DAC users.

Comparison of hepatitis B and SARS-CoV2 vaccination rates in people who attended Drugs and Addiction Centres.

Background and aims: 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. Design: 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. Findings: 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 (p < 0.001). Conclusion: 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.

Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418.

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.

Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Perception of HIV physicians in Spain towards diagnosis and management of neuropsychiatric comorbidities in people with HIV.

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.

Acute hepatitis B among HIV positive persons: A two-decade review of cases from a Spanish cohort.

PURPOSE: To review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades. METHODS: Retrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc. RESULTS: Out of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01-0.04) per 100 patient-year in the entire population and 0.06 (0.01-0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (ß=-0.006; p=0.047). All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis. CONCLUSION: The incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.

Acute hepatitis B among HIV positive persons: A two-decade review of cases from a Spanish cohort / Hepatitis B aguda en pacientes infectados por VIH en las dos últimas décadas en una cohorte española

ObjetivoRevisar la incidencia y las características de la hepatitis B aguda (HAB), en pacientes infectados por VIH en seguimiento durante las dos últimas décadas.MétodosRevisión retrospectiva de los casos de HAB en la cohorte de pacientes infectados por VIH y seguimiento en el Hospital Universitario La Paz, entre los años 2000 y 2018. La HAB se definió como la reciente aparición del AgS frente al virus de la hepatitis B (VHB) y anticuerpos anti-HBc+ de tipo IGM.ResultadosSe siguieron 5.443 pacientes VIH+, de ellos, 3.098 sin contacto previo con el VHB (anti-HBc negativo). Diagnosticamos 18 casos de HAB, lo que supone una incidencia de 0,02 (0,01-0,04) por 100 pacientes-año en toda la población y 0,06 (0,01-0,1) por 100 pacientes-año en aquellos anti-HBc negativo. Observamos una disminución significativa en la incidencia a lo largo de los años (β = -0,006; p = 0,047).Los 18 pacientes eran hombres y la mayoría (16) tenían sexo con hombres. En cuatro casos, la HAB se produjo en pacientes vacunados sin respuesta. Quince pacientes estaban sin tratamiento frente al VIH (TAR), dos recibían TAR sin drogas frente al VHB y uno tenía TAR con lamivudina, pero no tenofovir. No observamos ninguna hepatitis B grave, pero dos pacientes (11%) desarrollaron una hepatitis crónica B.ConclusiónLa incidencia de la HAB en pacientes VIH+ en nuestro hospital es baja y ha disminuido en los últimos 20 años. Aun así, seguimos viendo casos en pacientes sin protección para el VHB: sin vacunar o vacunados sin respuesta, que no reciben tenofovir.

PurposeTo review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades.MethodsRetrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc.ResultsOut of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01–0.04) per 100 patient-year in the entire population and 0.06 (0.01–0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (β=−0.006; p=0.047).All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis.ConclusionThe incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.

Seroreversion of IgG anti-HEV in HIV cirrhotic patients: A long-term multi-sampling longitudinal study.

The aim of our study was to evaluate HEV antibody kinetics in HIV/HCV-coinfected patients with cirrhosis. A longitudinal retrospective study was designed. Patients were followed up every 6 months; anti-HEV IgG and IgM antibodies levels and HEV-RNA by qPCR were analysed. The prevalence and incidence of every HEV infection marker were calculated. The kinetics of anti-HEV IgG and IgM during the follow-up were evaluated. Seventy-five patients comprised the study population. The seroprevalence observed was 17.3%. None showed IgM antibodies or HEV-RNA at baseline. None showed detectable HEV viral load during the study period. After a median follow-up of 5.1 years, two of 62 seronegative patients (3.2%) seroconverted to IgG antibody. The incidence for IgM was 2.7%. Of the 13 patients with IgG seropositivity at baseline, five (38.5%) seroreverted. Meanwhile, of the two patients who exhibited IgM positivity during the study, one (50%) showed intermittent positivity. We found that HEV seropositivity is common in HIV/HCV-coinfected cirrhotic patients. A remarkable rate of IgG seroreversions and IgM intermittence was found, limiting the use of antibodies for the diagnosis of HEV infection in this population.

Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation.

BACKGROUND: The ability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to maintain virologic suppression in participants with M184V and/or M184I resistance mutations from historical genotypic reports when switching from a tenofovir disoproxil fumarate-based or abacavir (ABC)-based regimen was investigated. SETTING: Phase IIIb, 48-week, open-label, single-arm, multicenter, clinical trial (NCT02616029). METHODS: Virologically suppressed adults with HIV and documented M184V/I on historical genotypic records switched to E/C/F/TAF from a tenofovir disoproxil fumarate-based or ABC-based regimen. The primary end point was HIV-1 RNA of <50 copies per milliliter at week 12 using pure virologic response (PVR). Secondary end points included HIV-1 RNA of <50 copies per milliliter at weeks 24/48 (PVR) and at weeks 12, 24, and 48 (Food and Drug Administration snapshot algorithm), and change in CD4+ count at weeks 12, 24, and 48. RESULTS: M184V alone was reported in 82.8% of 64 participants; 9.4% and 7.8% had M184I and M184V/I, respectively, and 43.8% had archived M184V/I (baseline DNA). All (62/62 with available data, 100%, 95% confidence interval 94.2% to 100%) participants maintained PVR at weeks 12, 24, and 48. By Food and Drug Administration snapshot algorithm, one participant had HIV-1 RNA of ≥50 copies per milliliter (week 12); confirmatory HIV-1 RNA was <50 copies per milliliter. No significant changes were observed in CD4+ cell count. Drug-related adverse events (AEs) were reported by 10 (15.6%) participants. Six (9.4%) and 5 (7.8%) participants had grade 3-4 AEs or serious AEs, respectively (none drug related). CONCLUSIONS: The presence of the resistance mutations M184V/I did not jeopardize the efficacy of switching to E/C/F/TAF in virologically suppressed adults. High rates of virologic suppression were maintained throughout 48 weeks of therapy and treatment was well tolerated.

Acute hepatitis B among HIV positive persons: A two-decade review of cases from a Spanish cohort.

PURPOSE: To review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades. METHODS: Retrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc. RESULTS: Out of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01-0.04) per 100 patient-year in the entire population and 0.06 (0.01-0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (ß=-0.006; p=0.047). All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis. CONCLUSION: The incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.

Randomized Trial Evaluating the Neurotoxicity of Dolutegravir/Abacavir/Lamivudine and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: GESIDA 9016.

BACKGROUND: Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. METHODS: We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. RESULTS: Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. CONCLUSIONS: Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.

Cerebrospinal fluid viral escape in aviremic HIV-infected patients receiving antiretroviral therapy: prevalence, risk factors and neurocognitive effects.

BACKGROUND: During antiretroviral therapy, HIV RNA can be detected in cerebrospinal fluid (CSF) when it is undetectable in plasma, a condition termed 'CSF viral escape'. The aim of the current study was to determine the prevalence and risk factors for CSF viral escape in two large cohorts in the USA. METHODS: A total of 1264 HIV-infected volunteers enrolled in two US cohorts at their most recent visit between 2003 and 2011 were included in this cross-sectional analysis if their HIV RNA level in plasma was less than 50 copies/ml while receiving stable antiretroviral therapy (ART) (>6 months) and if they had HIV RNA measured in CSF at their most recent visit between 2003 and 2011. Potential risk factors were identified using univariable and multivariable regression. RESULTS: CSF viral escape was detected in 55 adults (4.4%; 95% CI: 3.4-5.6), who had a median CSF HIV RNA of 155 copies/ml [interquartile range (IQR: 80-283)]. Patients with or without CSF viral escape had similar rates of neurocognitive impairment (38.2 vs. 37.7%; P = 0.91). CSF viral escape was independently associated with the use of ritonavir-boosted protease inhibitors [odds ratio (OR): 2.0; 95% CI: 1.1-3.8] or unboosted atazanavir (OR: 5.1; 95% CI: 1.3-16.1), CSF pleocytosis (OR: 7.6; 95% CI: 4.2-13.7) and abnormal CSF total protein (OR: 2.1; 95% CI: 1.1-3.7). CONCLUSIONS: In this large study of aviremic patients receiving ART, CSF viral escape was uncommon and was linked to evidence of central nervous system inflammation and the use of protease inhibitors, but not with worse neurocognitive performance.

Impact of Nucleos(t)ide Reverse Transcriptase Inhibitors on Blood Telomere Length Changes in a Prospective Cohort of Aviremic HIV-Infected Adults.

Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. Methods: 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. Results: 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 nucleos[t]ide 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. Discussion: 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.

Neurocognitive safety after 96 weeks on dual therapy with atazanavir/ritonavir plus lamivudine: results of the neurocognitive substudy of the SALT randomized clinical trial.

Background: Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment. Methods: We present the 96 week results of a neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96. Results: The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS [week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471] were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90). Conclusions: Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed.