Cerebrospinal fluid exposure to bictegravir/emtricitabine/tenofovir in HIV-1-infected patients with CNS impairment

2021 ◽  
Author(s):  
Thibaut Gelé ◽  
Antoine Chéret ◽  
Alicia Castro Gordon ◽  
Lionelle Nkam ◽  
Valérie Furlan ◽  
...  
Keyword(s):  
Real Life ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Hiv Cure ◽  
Crucial Component ◽  
Total Plasma Concentration ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Csf Concentration ◽  
Hiv 1

Abstract Objectives The penetration of antiretroviral drugs into deep compartments, such as the CNS, is a crucial component of strategies towards an HIV cure. This study aimed to determine CSF concentrations of bictegravir, emtricitabine and tenofovir in patients with HIV-related CNS impairment (HCI) enrolled in a real-life observational study. Methods Patients with HCI treated by optimized ART, including bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 1 month were enrolled. Plasma and CSF concentrations were measured by quality control-validated assays (LC-MS/MS). The inhibitory quotient (IQARV) was calculated as the ratio of unbound (bictegravir) or total (emtricitabine and tenofovir) concentration to half (or 90%) maximal inhibitory concentration for bictegravir (or emtricitabine and tenofovir). All numerical variables are expressed as median (range). Results Twenty-four patients (nine women) were enrolled. The age was 45 (26–68) years. Unbound bictegravir and total emtricitabine and tenofovir CSF concentrations were 4.4 (1.6–9.6), 84.4 (28.6–337.4) and 1.6 (0.7–4.3) ng/mL, respectively. The unbound bictegravir CSF fraction was 34% (15%–82%) versus 0.33% (0.11%–0.92%) in plasma. Three patients had an IQARV above unity for the three antiretrovirals. Factors positively associated with the CSF concentration (unbound for bictegravir) were age and total plasma concentration for the three antiretrovirals. Patients aged over 51 years had higher CSF concentrations (unbound for bictegravir). Conclusions We observed low CSF exposure to bictegravir, emtricitabine and tenofovir. These results suggest that BIC/FTC/TAF should be used with caution as first-line treatment for people living with HIV with HCI under 51 years of age.

scholarly journals Switching to a Bictegravir Single Tablet Regimen in Elderly People Living with HIV-1: Data Analysis from the BICTEL Cohort

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 76
Author(s):  
Alessandro Lazzaro ◽  
Elio Gentilini Cacciola ◽  
Cristian Borrazzo ◽  
Giuseppe Pietro Innocenti ◽  
Eugenio Nelson Cavallari ◽  
...  
Keyword(s):  
T Cells ◽  
Real Life ◽  
Total Body Weight ◽  
P Value ◽  
People Living With Hiv ◽  
Single Tablet Regimen ◽  
Total Body ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hiv 1

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 (p < 0.033). Among the overall population, we observed an increase in CD4+ T cells count by 30.1% (p-value < 0.001), in CD8+ T cells count by 7.1% (p-value = 0.004) and in CD4+/CD8+ ratio by 21.5% (p-value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% (p-value < 0.001) and LDL by 6.8% (p-value = 0.007). Total body weight increased by 1.8% (p-value = 0.014) and BMI by 4.2% (p-value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55.

scholarly journals Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV–1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58)

2020 ◽  
Author(s):  
Arkaitz Imaz ◽  
Juan M Tiraboschi ◽  
Jordi Niubó ◽  
Javier Martinez-Picado ◽  
Mackenzie L Cottrell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Research Network ◽  
People Living With Hiv ◽  
Limit Of Quantification ◽  
Immunodeficiency Virus ◽  
Liquid Chromatography Tandem Mass ◽  
Half Maximal Effective Concentration ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)–1 RNA in genital fluids and the rectum have not yet been addressed. Methods We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay. Results The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was &gt;40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41–3.79), 4.19 (2.98–4.70), and 2.56 (1.61–3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1–923) ng/mL, 74.1 (6.0–478.5) ng/g, and 61.6 (14.4–1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively. Conclusions BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL). Clinical Trials Registration EudraCT 2018-002310-12.

scholarly journals INCIDENCE AND RISK FACTORS OF RENAL IMPAIRMENT IN HIV-1 INFECTED PATIENTS RECEIVING TENOFOVIR BASED ANTIRETROVIRAL THERAPY IN A SOUTH INDIAN HOSPITAL

2017 ◽  
Vol 9 (5) ◽  
pp. 152
Author(s):  
A. Pramod Kumar ◽  
G. Parthasarathi ◽  
A. P. Sudheer ◽  
S. N. Mothi ◽  
V. H. T. Swamy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Impairment ◽  
Real Life ◽  
Transcriptase Inhibitor ◽  
People Living With Hiv ◽  
South Indian ◽  
Severe Impairment ◽  
Living With Hiv ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Objective: To identify the incidence and risk factors of tenofovir (TDF) induced nephrotoxicity among People Living with HIV/AIDS (PLHA) receiving TDF-based anti-retroviral therapy (ART) in a South Indian Hospital.Methods: A retrospective cohort study was conducted among HIV-infected ART naïve patients taking TDF as part of either a first-line or second-line ART between July 2013 and June 2015 at Asha kirana Hospital Mysore, India.Results: A total of 380 patients have been initiated on TDF-based ART. Out of these, 335 patients were on tenofovir+lamivudine+efavirenz, 30 patients were on the tenofovir+lamivudine+nevirapine regimen and 25 patients were on tenofovir+lamivudine+atazanavir/ritonavir regimen. Renal impairment was documented for 35 patients with 9.21% incidence. 34% of renal impaired patients had a severe impairment with eGFR<30 ml/min. Elderly patients (>61 y) had higher chances of developing TDF toxicity compared to adult patients (P=0.0018). Other possible risk factors for TDF-induced renal impairment was CD4>200 (P=0.003). TDF was withdrawn and substituted with Nucleoside Reverse Transcriptase Inhibitor (NRTI) drug following the diagnosis of renal impairment.Conclusion: TDF-associated renal impairment was not uncommon in real-life practice and considered as a frequent complication during treatment with TDF. Risk factors for developing renal impairment include increasing age and CD4>200 cells.

scholarly journals Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 14
Author(s):  
Barbara Rossetti ◽  
Valentina Borgo ◽  
Arianna Emiliozzi ◽  
Marta Colaneri ◽  
Giacomo Zanelli ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Virus Infection ◽  
Viral Hepatitis ◽  
Hepatitis Virus ◽  
People Living With Hiv ◽  
Non Invasive ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hepatitis Virus Infection ◽  
Hiv 1

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

scholarly journals Insights into the Gene Expression Profiles of Active and Restricted Red/Green-HIV+ Human Astrocytes: Implications for Shock or Lock Therapies in the Brain

2020 ◽  
Vol 94 (6) ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Anuja Ghorpade ◽  
Kathleen Borgmann
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Antiretroviral Drugs ◽  
Gene Expression Patterns ◽  
People Living With Hiv ◽  
Human Astrocytes ◽  
Living With Hiv ◽  
Hiv 1

ABSTRACT A significant number of people living with human immunodeficiency virus type 1 (HIV-1) suffer from HIV-associated neurocognitive disorders (HAND). Many previous studies investigating HIV in astrocytes as a heterogenous population have established the relevance of astrocytes to HIV-associated neuropathogenesis. However, these studies were unable to differentiate the state of infection, i.e., active or latent, or to evaluate how this affects astrocyte biology. In this study, the pseudotyped doubly labeled fluorescent reporter red/green (R/G)-HIV-1 was used to identify and enrich restricted and active populations of HIV+ astrocytes based on the viral promoter activity. Here, we report that the majority of human astrocytes restricted R/G-HIV-1 gene expression early during infection and were resistant to reactivation by vorinostat and interleukin 1β. However, actively infected astrocytes were inducible, leading to increased expression of viral proteins upon reactivation. R/G-HIV-1 infection also significantly decreased the cell proliferation and glutamate clearance ability of astrocytes, which may contribute to excitotoxicity. Moreover, transcriptome analyses to compare gene expression patterns of astrocyte harboring active versus restricted long terminal repeats (LTRs) revealed that the gene expression patterns were similar and that the active population demonstrated more widespread and robust changes. Our data suggest that harboring the HIV genome profoundly alters astrocyte biology and that strategies that keep the virus latent (e.g., block and lock) or those that reactivate the latent virus (e.g., shock and kill) would be detrimental to astrocyte function and possibly augment their contributions to HAND. IMPORTANCE More than 36 million people are living with HIV-1 worldwide, and despite antiretroviral therapy, 30 to 50% of the people living with HIV-1 suffer from mild to moderate neurocognitive disorders. HIV-1 reservoirs in the central nervous system (CNS) are challenging to address due to low penetration of antiretroviral drugs, lack of resident T cells, and permanent integration of provirus into neural cells such as microglia and astrocytes. Several studies have shown astrocyte dysfunction during HIV-1 infection. However, little is known about how HIV-1 latency affects their function. The significance of our research is in identifying that the majority of HIV+ astrocytes restrict HIV expression and were resistant to reactivation. Further, simply harboring the HIV genome profoundly altered astrocyte biology, resulting in a proinflammatory phenotype and functional changes. In this context, therapeutic strategies to reactivate or silence astrocyte HIV reservoirs, without excising proviral DNA, will likely lead to detrimental neuropathological outcomes during HIV CNS infection.

Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial

2021 ◽  
Author(s):  
Thierry Prazuck ◽  
Renaud Verdon ◽  
Gwenaël Le Moal ◽  
Faïza Ajana ◽  
Louis Bernard ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Maintenance Strategy ◽  
Open Label ◽  
Hiv Dna ◽  
Triple Regimen ◽  
Living With Hiv ◽  
And Control ◽  
Hiv 1

Abstract Objectives Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. Methods TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA &lt;2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) &lt;50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). Results Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL &lt; 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI –5.9 to 10.7; PP difference 3.4%, 95% CI –4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI –1.9 to 9.4). All VFs were resuppressed after treatment modification. Conclusions Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

PERAN WARGA PEDULI AIDS CAHAYA CARE TUREN DALAM MENINGKATKAN KUALITAS HIDUP ODHA

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Tri Nurhudi Sasono
Keyword(s):  
Quality Of Life ◽  
Antiretroviral Drugs ◽  
P Value ◽  
People Living With Hiv ◽  
Purposive Sampling ◽  
Significant Difference ◽  
Development Goals ◽  
Living With Hiv ◽  
Hiv Aids

Abstract : Indicator of the health welfare through Sustanable Development Goals (SDGs) is to reduce the incidence of HIV-AIDS, decrease the rate of the epidemic and maintain the quality of life of people living with HIV-AIDS (PLWHA). Trend cases of HIV-AIDS is the most recent spread among people, especially housewives. In Malang until 2015 found 278 Housewife of 409 cases of AIDS. The prevalence of HIV-AIDS in Malang Regency is ranked second after Surabaya city in East Java. For the importance of public participation and citizen care AIDS Cahaya Care Turen take responsibility for the condition. Determination Rule Goverment number 2 2015 year on the Participation of the community response to HIV-AIDS in Malang as a legal rule. Concerned Citizens activities AIDS (WPA). WPA Cahaya Care Turen is increases HIV risk and quality of life PLWHA. The purpose of this study was to determine the role of Citizens AIDS Cahaya Care Quality of Care Turen against people living with HIV in Puskesmas Turen Malang. The study design using a quasi-experimental, with purposive sampling using a sampling technique. Total number of research subjects 23. Based on test results obtained with the Wilcoxon p value <0.005, which means that there is a significant difference before and after PLWHA joining participated in the WPA Cahaya Care Turen. The conclusion of this study is WPA activities involving people living with HIV and at risk groups can optimize compliance with antiretroviral drugs that have an impact on improving the quality of life of PLHIV. Suggestions in this research is done WPA Program activities are structured and ongoing cross-sector in order to improve the quality of life and empower PLWHA.Keywords : WPA Cahaya Care Turen, Quality of life, PLWHA Abstrak : Salah satu indikator kesejahteraan kesehatan melalui Sustanable Development Goals (SDGs) adalah menekan angka kejadian HIV-AIDS, menurunkan laju epidemik dan mempertahankan kualitas hidup Orang dengan HIV-AIDS (ODHA). Trend kasus HIV-AIDS terkini terbanyak adalah menjangkit dikalangan masyarakat khususnya pada ibu rumah tangga. Kabupaten Malang sampai dengan tahun 2015 ditemukan 278 Ibu Rumah Tangga dari 409 kasus AIDS. Prevalensi HIV-AIDS di Kabupaten Malang ini merupakan peringkat kedua di Jawa Timur setelah Kota Surabaya. Untuk itu pentingnya peran serta masyarakat dan warga peduli AIDS Cahaya Care Turen ikut bertanggung jawab terhadap kondisi tersebut. Penetapan Peraturan Bupati Malang no.2 th.2015 tentang Peran serta masyarakat penanggulangan HIV-AIDS di Kabupaten Malang diharapkan dapat mengurangi risiko penularan HIV dan meningkatkan kualitas hidup ODHA. Tujuan dari penelitian ini adalah untuk mengetahui Peran Warga Peduli AIDS Cahaya Care Turen terhadap Kualitas ODHA Di Wilayah Kerja Puskesmas Turen Kabupaten Malang. Desain penelitian menggunakan quasi eksperimen, dengan teknik sampling menggunakan purposive sampling. Jumlah subyek penelitian sejumlah 23. Berdasarkan hasil uji dengan Wilcoxon didapatkan nilai p value < 0.005 yang berarti bahwa terdapat perbedaan bermakna sebelum dan sesudah ODHA bergabung mengikuti kegiatan WPA Cahaya Care Turen. Kesimpulan dalam penelitian ini adalah kegiatan WPA dengan melibatkan ODHA dan kelompok beresiko dapat mengoptimalkan kepatuhan obat ART sehingga berdampak terhadap peningkatan kualitas hidup ODHA. Saran dalam penelitian ini adalah dilakukannya Program kegiatan WPA yang terstruktur dan berkesinambungan lintas sektor guna meningkatkan kualitas hidup dan memberdayakan ODHA.     Kata kunci : WPA Cahaya Care Turen, kualitas hidup, ODHA

scholarly journals Antiretroviral Drugs Impact Autophagy with Toxic Outcomes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman
Keyword(s):  
Quality Control ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Viral Suppression ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Foreign Material ◽  
Complete Understanding ◽  
Living With Hiv ◽  
Target Effects

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.

scholarly journals HIV-1 subverts the complement system in semen to enhance viral transmission

2021 ◽  
Author(s):  
Bernadien M. Nijmeijer ◽  
Marta Bermejo-Jambrina ◽  
Tanja M. Kaptein ◽  
Carla M. S. Ribeiro ◽  
Doris Wilflingseder ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Virus Transmission ◽  
Sexual Contact ◽  
Target Cells ◽  
People Living With Hiv ◽  
Lectin Receptor ◽  
Pre Treatment ◽  
Living With Hiv ◽  
Hiv 1

AbstractSemen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.

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