Antiretroviral drug reduction in highly experienced HIV-infected patients receiving a multidrug regimen: the ECOVIR study

2019 ◽  
Vol 74 (9) ◽  
pp. 2716-2722
Author(s):  
Marc-Antoine Valantin ◽  
Lise Durand ◽  
Marc Wirden ◽  
Lambert Assoumou ◽  
Fabienne Caby ◽  
...  
Keyword(s):  
Viral Suppression ◽  
Drug Regimen ◽  
Antiretroviral Drugs ◽  
Expert Advice ◽  
Resistance Mutations ◽  
Duration Of Treatment ◽  
Kaplan Meier ◽  
Virological Success ◽  
High Level ◽  
A Prospective Study

Abstract Objectives In a context of life-long therapy, we asked whether it could be possible to reduce the number of antiretroviral drugs without jeopardizing viral suppression. Methods ECOVIR was a prospective study aiming to assess whether in patients on combination ART with ≥4 antiretrovirals for ≥24 weeks and virally suppressed for ≥48 weeks, a drug-reduced (DR) regimen could be proposed. The intervention consisted of discontinuing genotypically less susceptible drugs to reach a DR regimen with ≤3 antiretrovirals. The primary endpoint was the proportion of patients maintaining viral suppression at week (W) 24. Results From 89 eligible individuals for the study, a DR regimen was proposed in 86 (97%) patients, of whom 71 were switched to a DR regimen. Baseline characteristics [median (IQR)] were: age 58 (53–65) years, duration of treatment 24 (21–26) years and viral suppression 8 (6–11) years. The cumulative resistance profile showed full resistance to lamivudine/emtricitabine (91%), abacavir (74%), efavirenz/nevirapine (70%), rilpivirine (56%), darunavir (q24h/q12h) (42%/29%), lopinavir (69%), atazanavir (71%) and raltegravir (24%). The final DR regimen consisted of a two-drug or three-drug regimen in 54 patients (76%) and in 17 patients (24%), respectively. The success rate of a DR regimen at W24 was 93.9% (95% CI 84.4–97.6, Kaplan–Meier estimate). Four patients experienced virological failure (at W4, W8 and W12), all with plasma viral load (pVL) <600 copies/mL and no emergence of resistance mutations. The DR strategy allowed a monthly cost saving of 36%. Conclusions In experienced patients with high-level resistance, individualized strategies based on expert advice can offer DR regimen options with fewer drug–drug interactions and a significant economic impact while ensuring virological success.

Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study

2019 ◽  
Vol 74 (9) ◽  
pp. 2742-2751 ◽  
Author(s):  
Christine Katlama ◽  
Lambert Assoumou ◽  
Marc-Antoine Valantin ◽  
Cathia Soulié ◽  
Esteban Martinez ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Success Rate ◽  
Bone Mineral ◽  
Viral Suppression ◽  
Dual Therapy ◽  
Integrase Inhibitor ◽  
Mineral Density ◽  
Type 1 Error ◽  
Virological Success ◽  
High Level

Abstract Background Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. Methods The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. Results One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%–99.9%) at week 48 and 98.7% (95% CI = 95.0%–99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%–97.5%) at week 48 and 92.7% (95% CI = 87.5%–95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (−8.1%), soluble CD14 decreased (−27%, P < 0.001) bone mineral density improved and BMI increased. Conclusions Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.

scholarly journals Sustained HIV viral suppression with dolutegravir, tenofovir, and emtricitabine as initial therapy despite high-level transmitted multi-class resistance

2021 ◽  
Author(s):  
Ellen H Nagami ◽  
Kinna Thakarar ◽  
Paul E Sax
Keyword(s):  
Viral Suppression ◽  
Drug Class ◽  
Drug Regimen ◽  
Initial Therapy ◽  
Strand Transfer ◽  
Antiretroviral Drug ◽  
Integrase Strand Transfer Inhibitors ◽  
Hiv Viral Suppression ◽  
High Level ◽  
Selection Of

Abstract Multi-class high-level transmitted HIV drug resistance is uncommon, and the selection of the optimal initial antiretroviral drug regimen may be challenging. We report a case of extensive transmitted multi-class resistance successfully treated with dolutegravir, tenofovir, and emtricitabine even though the baseline genotype demonstrated full susceptibility to only one drug class, the integrase strand transfer inhibitors. Our case highlights both the high resistance barrier of dolutegravir and the residual antiviral activity of nucleoside reverse transcriptase inhibitors despite extensive resistance on genotype.

scholarly journals 1382. A Prospective Epidemiological Study BK Polyomavirus DNAuria and DNAemia within the First Year after Kidney Transplantation

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S777-S777
Author(s):  
Pannawat Mongkolrattanakul ◽  
Jackrapong Bruminhent ◽  
Tanaya Siripoon ◽  
Punlop Wiwattanathum ◽  
Suchin Worawichawong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Tertiary Care ◽  
Chi Square ◽  
Low Level ◽  
Resource Limited ◽  
Kaplan Meier ◽  
Bk Polyomavirus ◽  
Student’S T ◽  
High Level ◽  
A Prospective Study

Abstract Background Screening and early detection for the preceding BK polyomavirus (BKV) DNAuria and DNAemia to prevent the occurrence of BK polyomavirus BKV-associated nephropathy (BKPyVAN) among kidney transplant (KT) recipients has not been universally utilized and never assessed in a setting where the resource is limited. Therefore, we aimed to investigate this entity’s incidence, risk factors, and outcome with this intervention at our institution. Methods A prospective study of KT recipients at a tertiary care transplant center in Bangkok, Thailand, was conducted between January 2019 and March 2020. All patients underwent preemptive monitoring of urine and plasma BKV DNA load, measured by quantitative real-time PCR at 1, 2, 3, 6, 9, and 12 months post-KT. Low- and high-level BKV DNAuria was defined as urine BKV DNA load of &lt; and &gt; 7log10 copies/mL, respectively. Low- and high-level BKV DNAemia was defined as plasma BKV DNA load of &lt; and &gt; 4log10 copies/mL, respectively. The incidences were calculated by Kaplan-Meier analysis. The chi-square or student’s T-test compared clinical characteristics between those with and without high-level BKV DNAuria as appropriate. Risk factors of high-level BKV DNAuria were analyzed using Cox proportional hazard model. Results Among 99 evaluable KT recipients, a mean (SD) age was 42 (11) years, 64.6% were male, and 69.6% received an induction immunosuppressive therapy. Within 12 months post-KT, the incidences of low-level BKV DNAuria, high-level BKV DNAuria, low-level BKV DNAemia, and high-level BKV DNAemia were 22.63%, 13.14%, 9.49%, and 5.11%, respectively. High panel reactive antibody (PRA) was associated with high-level BKV DNAuria at 6 and 12 months, (HR 1.02 [95% CI (1.00-1.04)], P=0.019) and (HR 1.02 [95% CI (1.00-1.04)], P=0.023), respectively. Underlying diabetes mellitus was associated with high-level BKV DNAuria (HR 3.49 [95% CI (1.28-9.51)], P=0.015) at six months; however, not at 12 months. There was no allograft rejection directly related to a reduction of immunosuppression for BKV infection observed. Conclusion BKPyV infection is also prevalent among KT recipients in a resource-limited setting, however, without unfavorable consequence. Those with high-level PRA and underlying diabetes could be at risk of high-level BKV DNAuria after KT. Disclosures All Authors: No reported disclosures

Immediate implantation in a patient with chronic generalized parodontitis and apical granuloma

2019 ◽  
Vol 24 (2) ◽  
pp. 145-149
Author(s):  
A. I. Musienko ◽  
K. I. Nesterova
Keyword(s):  
Tooth Extraction ◽  
Tooth Root ◽  
Duration Of Treatment ◽  
Promising Direction ◽  
Aesthetic Result ◽  
Bone Atrophy ◽  
Alveolar Tissue ◽  
High Level ◽  
Immediate Implantation

Relevance. Rehabilitation of patients with moderate to severe generalized periodontitis is a leading problem in periodontology. It was the determination of the prospects for immediate implantation in patients with chronic periodontitis, combined with the pathology of the tooth root and maxillary sinus.Materials and methods. A group of 94 people with periodontitis and chronic odontogenic rhinosinus was observed who underwent sinus surgical treatment, tooth extraction and one-stage implantation with FRP growth factor according to the author's technology.Results. The method showed high efciency on the basis of assessing the clinical, aesthetic result and restoration of bone density after surgery.Conclusions. The developed technology is a promising direction, it allows to combine a high level of sanation of alveolar tissue with the advantages of immediate implantation, prevents bone atrophy, helps reduce the duration of treatment and the number of surgical and orthopedic interventions.

scholarly journals GCT-10. CAN HIGH LEVEL SERUM hCG-β BE CONSIDERED EQUIVALENT TO A DIAGNOSIS OF CHORIOCARCINOMA IN PRIMARY CENTRAL NERVOUS SYSTEM GERM-CELL TUMOR?

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii329-iii330
Author(s):  
Hiroaki Motegi ◽  
Shigeru Yamaguchi ◽  
Yukitomo Ishi ◽  
Michinari Okamoto ◽  
Akihiro Iguchi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Good Prognosis ◽  
Cell Tumor ◽  
University Hospital ◽  
Kaplan Meier ◽  
Beta Human Chorionic Gonadotropin ◽  
High Level

Abstract BACKGROUND Primary central nervous system(CNS) choriocarcinoma(CC) is very rare and has the poorest prognosis among germ cell tumor (GCT). CC usually has extremely high level (HL) of serum beta-human chorionic gonadotropin (bhCG) over than 1,000 mIU/ml. Some studies assign HL bhCG cases to poor prognosis group even without biopsy. The purpose of this study was to find out if there was a good prognosis subset in the HL bh group. MATERIALS AND METHODS We analyzed 103 cases diagnosed with GCT from 1998 to 2019 in Hokkaido University Hospital and reviewed the literature of CNS CC and bhCG. Survival was assessed using Kaplan-Meier method and log-rank statistics between the group with CC component and that with no CC component but HL bhCG. RESULTS One out of 103 our cases was diagnosed as a mixed GCT with CC component and did not respond to treatment and died 9 months later. Two cases were treated as CC because of HL bhCG (1,226 and 2,739 mIU/ml) despite that the biopsy showed only germinomas and survived(105 and 37 months), that is, no CC component. Combining our cases with 69 cases in the literature, all 7 cases with no CC component but HL bhCG survived but the median survival of the other 65 cases with CC component was 38.2 months (P=0.02). CONCLUSION This study has a limitation of selection bias, however, it suggests that patients with no CC component but HL bhCG may have a better prognosis.

scholarly journals Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program

2021 ◽  
Vol 13 ◽  
pp. 175883592098055 ◽  
Author(s):  
Nikolaj Frost ◽  
Petros Christopoulos ◽  
Diego Kauffmann-Guerrero ◽  
Jan Stratmann ◽  
Richard Riedel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Survival Rates ◽  
Real Life ◽  
Progression Free Survival ◽  
Leptomeningeal Carcinomatosis ◽  
Resistance Mutations ◽  
Duration Of Treatment ◽  
Tp53 Mutations ◽  
Early Access ◽  
Access Program

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib. Patients and Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed. Results: In total, 52 patients were included [median age 57 years (range 32–81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1–4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4 months, 8.0 months, 54% and 13.0 months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6 months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8 month, HR 3.3, p = 0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p = 0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS. Conclusions: Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.

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 1010. Effective Management of HIV in Rural Georgia Using Telemedicine

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S533-S533
Author(s):  
Folake J Lawal ◽  
Arni S R Srinivasa Rao ◽  
Jose A Vazquez
Keyword(s):  
Rural Areas ◽  
Viral Suppression ◽  
Retrospective Chart Review ◽  
Cd4 Count ◽  
Hiv Care ◽  
Resistance Mutations ◽  
Remote Communities ◽  
Hiv Viral Load ◽  
Viral Control ◽  
Significant Difference

Abstract Background The increasing incidence of HIV and lack of care in rural areas contributes to the ongoing epidemic. The dearth of specialized health services within remote communities and access of this population to available services poses a challenge to HIV care. Telemedicine (TM) is a potential tool to improve HIV care in these remote communities, but little is known about its effectiveness when compared to traditional (face-to-face) (F2F) care. The objective of this study is to examine the effectiveness of HIV care delivered through TM, and compare to F2F care. Methods This is a retrospective chart review of all HIV positive patients who attended either the F2F clinic (Augusta, GA) or the TM clinic (Dublin, GA) between May 2017 to April 2018. Data extracted included demographics, CD4 count, HIV PCR, co-morbidities, dates of clinic attendance, HIV resistance mutations and ART changes. Viral suppression and gain in CD4 counts were compared. T-test was conducted to test differences in characteristics and outcomes between the two groups. Results 385 cases were included in the study (52.5% black, 82% females, F2F=200, TM=185). Mean CD4 count in the TM group was statistically higher (643.9 cells/mm3) than the F2F group (596.3 cells/mm3) (p&lt; 0.001). There was no statistically significant difference in mean HIV viral load (F2F= 416.8 cp/ml, TM=713.4 cp/ml, p=0.3) and rates of year-round viral control (F2F= 73% vs TM = 77% p= 0.54). 38 patients achieved viral suppression during the study period (F2F= 24, TM =14) with a mean change of -3.34 x 104 vs -1.24 x 104, respectively. The difference in mean change was not statistically significant by Snedacor’s W Statistics. This indicates there was no significant difference between the two populations in terms of mean viral suppression among patients who were otherwise not suppressed before the study period. Conclusion To achieve an HIV cure, HIV care is required to extend to rural areas of the country and the world. Through delivery of care using TM, trained specialists can target communities with little or no health care. Moreover, use of TM achieves target outcome measures comparable to F2F clinics. Increase in the use of TM will improve the access to specialty HIV care and help achieve control of HIV in rural communities. Disclosures All Authors: No reported disclosures

scholarly journals Medicine treatment of glaucoma in Australia 2012–2019: prevalence, incidence and persistence

2021 ◽  
Vol 6 (1) ◽  
pp. e000921
Author(s):  
Benjamin Daniels ◽  
Paul Healey ◽  
Claudia Bruno ◽  
Iain Kaan ◽  
Helga Zoega
Keyword(s):  
Medical Therapy ◽  
Median Duration ◽  
Duration Of Treatment ◽  
Treatment Persistence ◽  
Prostaglandin Analogues ◽  
The Past ◽  
Kaplan Meier ◽  
Glaucoma Treatment ◽  
Persistence To Treatment

ObjectiveMedical therapy can halt or significantly slow the progression of glaucoma if medicines are used in accordance with the guidelines. We used dispensing claims for a 10% sample of all Australians dispensed publicly subsidised glaucoma medicines to determine the prevalence and incidence of glaucoma medicine treatment and to examine treatment persistence between July 2012 and June 2019.MethodsWe estimated incidence and prevalence per 10 000 population for Australian financial years (1 July to 30 June). We defined prevalence as at least one dispensing of any glaucoma medicine and incidence as a dispensing of any glaucoma medicine with no previous dispensing during the preceding 12 months. We estimated duration of treatment for a cohort initiating glaucoma medicines and used Kaplan-Meier methods to estimate the proportion of people persisting on treatment at 6, 12, 18 and 36 months after initiation. We stratified analyses by the number of repeats prescribed at initiation, age, sex and medicine class.ResultsPrevalence remained stable over the study period at around 180/10 000 people/year; incidence was also stable around 36/10 000/year. Among 34 900 people initiating glaucoma medicines, 37.0% remained on treatment at 6 months from initiation, 29.8% at 12 months and 19.2% at 36 months. Median duration of treatment was 13.2 months (IQR: 2.5—not reached) for people initiating prostaglandin analogues and less than 3 months for those initiating other medicine classes.ConclusionPrevalence and incidence of glaucoma treatment have not changed in Australia over the past decade. Persistence to treatment increased with age but remained poor throughout the study period.

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