scholarly journals Treatment with commonly used antiretroviral drugs induces a type I/III interferon signature in the gut in the absence of HIV infection

2019 ◽  
Author(s):  
Sean M. Hughes ◽  
Claire N. Levy ◽  
Fernanda L. Calienes ◽  
Joanne D. Stekler ◽  
Urvashi Pandey ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Cellular Proliferation ◽  
Rectal Biopsy ◽  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
Type I ◽  
Treatment And Prevention ◽  
Tenofovir Gel ◽  
Droplet Pcr ◽  
Exposure Prophylaxis

AbstractTenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here we assessed the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induced type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r=0.91) and between the rectum and duodenum (r=0.81). Gene set testing also indicated stimulation of type I/III pathways in the ectocervix, as well as of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence staining confirmed IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN-I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.

Long-Acting HIV Drugs for Treatment and Prevention

2019 ◽  
Vol 70 (1) ◽  
pp. 137-150 ◽  
Author(s):  
Roy M. Gulick ◽  
Charles Flexner
Keyword(s):  
Drug Regimen ◽  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
Phase Iii ◽  
Treatment And Prevention ◽  
Drug Concentrations ◽  
Phase Iii Trials ◽  
Long Acting ◽  
Hiv Drugs ◽  
Exposure Prophylaxis

Antiretroviral drugs have revolutionized the treatment and prevention of HIV infection; however, adherence is critical for sustained efficacy. Current HIV treatment consists of three-drug regimens, and current HIV pre-exposure prophylaxis (PrEP) consists of a two-drug regimen; both generally require adherence to once-daily dosing. Long-acting formulations are useful in the treatment and prevention of other conditions (e.g., contraceptives, antipsychotics) and help promote adherence. Newer long-acting formulations of approved and investigational antiretroviral drugs in existing and newer mechanistic classes are under study for HIV treatment and prevention, including some phase III trials. Although long-acting antiretroviral drugs hold promise, some clinical challenges exist, including managing side effects, drug-drug interactions, pregnancy, and long-lasting drug concentrations that could lead to the development of drug resistance. This review aims to summarize currently available information on long-acting antiretroviral drugs for HIV treatment and prevention.

scholarly journals Tonse Pamodzi: Developing a combination strategy to support adherence to antiretroviral therapy and HIV pre-exposure prophylaxis during pregnancy and breastfeeding

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253280
Author(s):  
Lauren M. Hill ◽  
Friday Saidi ◽  
Kellie Freeborn ◽  
K. Rivet Amico ◽  
Nora E. Rosenberg ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Intervention Development ◽  
Hiv Treatment ◽  
Child Health Services ◽  
Maternal Child Health ◽  
Combination Strategy ◽  
Antiretroviral Adherence ◽  
Treatment And Prevention ◽  
Adherence Support ◽  
Exposure Prophylaxis

To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi (“all of us together”), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT.

scholarly journals Injectable Antiretroviral Drugs: Back to the Future

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 228
Author(s):  
Marco Berruti ◽  
Niccolò Riccardi ◽  
Diana Canetti ◽  
Sergio Lo Caputo ◽  
Lucia Taramasso ◽  
...  
Keyword(s):  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
People Living With Hiv ◽  
Virologic Suppression ◽  
Treatment Regimens ◽  
The People ◽  
Frequent Administration ◽  
The Future ◽  
Exposure Prophylaxis ◽  
Living With Hiv

Current HIV treatment regimens provide sustained virologic suppression, at least partially restore the immune system and have limited side effects; however, they do not allow viral eradication and they are burdened by daily pill intake with a life-long commitment for the people living with HIV (PHIV). Injectable agents might represent a turning point in the care of PHIV, allowing less frequent administration of antiretroviral treatment (ART), more widespread use of pre-exposure prophylaxis (PrEP) and more stable drug levels in the blood, thus increasing the odds to get closer to end the HIV pandemic. The aim of this manuscript is to give a comprehensive review of injectable antiretrovirals that have been used in the past, which are available now, will be available in the future, and their role in the treatment of HIV infection

scholarly journals Implementing a Status-Neutral Approach to HIV in the Asia-Pacific

2020 ◽  
Vol 17 (5) ◽  
pp. 422-430
Author(s):  
Nittaya Phanuphak ◽  
Reshmie Ramautarsing ◽  
Tanat Chinbunchorn ◽  
Rena Janamnuaysook ◽  
Supabhorn Pengnonyang ◽  
...  
Keyword(s):  
Health Care ◽  
Health Care Systems ◽  
Scale Up ◽  
Hiv Treatment ◽  
Asia Pacific ◽  
Treatment And Prevention ◽  
Prep Implementation ◽  
Care Systems ◽  
Wide Scale ◽  
Exposure Prophylaxis

Abstract Purpose of Review Globally, “undetectable equals untransmittable (U=U)” and “pre-exposure prophylaxis (PrEP)” have become crucial elements in HIV treatment and prevention programs. We reviewed the implementation of U=U and PrEP among countries in the Asia-Pacific region. Recent Findings U=U and PrEP uptakes were limited and slow in the Asia-Pacific. Inadequate knowledge among health care practitioners and pervasive stigma towards individuals living with HIV and their sexual lives are key barriers for the integration of U=U into clinical practice. Paternalistic and hierarchical health care systems are major obstacles in PrEP implementation and scale-up. Countries with the most advanced PrEP implementation all use community-based, nurse-led, and key population-led service delivery models. Summary To advance U=U and PrEP in the Asia-Pacific, strategies targeting changes to practice norm through wide-scale stakeholders’ training and education, making use of online health care professional influencers, and utilizing financial mechanism should be further explored through implementation research.

scholarly journals The Costs of Creatinine Testing in the Context of a HIV Pre-Exposure Prophylaxis Demonstration Project in Eswatini

2021 ◽  
Author(s):  
Stefan Kohler ◽  
Rumbidzai Ndungwani ◽  
Mark Burgert ◽  
Dumile Sibandze ◽  
Sindy Matse ◽  
...  
Keyword(s):  
High Throughput ◽  
Government Procurement ◽  
Hiv Treatment ◽  
Demonstration Project ◽  
Public Health Care ◽  
Fixed Costs ◽  
Activity Based Costing ◽  
Laboratory Equipment ◽  
Treatment And Prevention ◽  
Exposure Prophylaxis

AbstractHIV treatment and prevention as well as other chronic disease care can require regular kidney function assessment based on a creatinine test. To assess the costs of creatinine testing in a public health care system, we conducted activity-based costing during a HIV pre-exposure prophylaxis (PrEP) demonstration project in the Hhohho region of Eswatini. Resource use was assessed by a laboratory technician and valued with government procurement prices, public sector salaries, and own cost estimates. Obtaining a blood sample in a clinic and performing a creatinine test in a high-throughput referral laboratory (> 660,000 blood tests, including > 120,000 creatinine tests, in 2018) were estimated to have cost, on average, $1.98 in 2018. Per test, $1.95 were variable costs ($1.38 personnel, ¢39 consumables, and ¢18 other costs) and ¢2.6 were allocated semi-fixed costs (¢1.1 laboratory equipment, ¢0.85 other, ¢0.45 consumables, and ¢1.3 personnel costs). Simulating different utilization of the laboratory indicated that semi-fixed costs of the laboratory (e.g., equipment purchase or daily calibration of the chemistry analyzer) contributed less than variable costs (e.g., per-test personnel time and test reagents) to the average creatinine test cost when certain minimum test numbers can be maintained. Our findings suggest, first, lower creatinine testing costs than previously used in cost and cost-effectiveness analyses of HIV services and, second, that investment in laboratory equipment imposed a relatively small additional cost on each performed test in the high-throughput referral laboratory.

Nanoparticles and Its Implications in HIV/AIDS Therapy

2020 ◽  
Vol 17 (4) ◽  
pp. 448-456 ◽  
Author(s):  
Victor B. Oti
Keyword(s):  
Direct Injection ◽  
Oral Intake ◽  
Public Health Problem ◽  
Antiretroviral Drugs ◽  
The Body ◽  
Viral Agent ◽  
Treatment And Prevention ◽  
Prevention And Treatment ◽  
Hiv Aids

The use of Antiretroviral drugs in treating HIV/ AIDS patients has enormously increased their life spans with serious disadvantages. The virus infection still remains a public health problem worldwide with no cure and vaccine for the viral agent until now. The use of nanoparticles (NPs) for the treatment and prevention of HIV/AIDS is an emerging technology of the 21st century. NPs are solid and colloid particles with 10 nm to <1000 nm size range; although, less than 200 nm is the recommended size for nanomedical usage. There are NPs with therapeutic capabilities such as liposomes, micelles, dendrimers and nanocapsules. The particle enters the body mainly via oral intake, direct injection and inhalation. It has been proven to have potentials of advancing the prevention and treatment of the viral agent. Certain NPs have been shown to have selftherapeutic activity for the virus in vitro. Strategies that are novel are emerging which can be used to improve nanotechnology, such as genetic treatment and immunotherapy. In this review, nanoparticles, the types and its characteristics in drug delivery were discussed. The light was furthermore shed on its implications in the prevention and treatment of HIV/AIDS.

scholarly journals The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data?

2021 ◽  
Vol 20 ◽  
pp. 232595822110090
Author(s):  
Kimberly K. Scarsi ◽  
Susan Swindells
Keyword(s):  
Medication Adherence ◽  
Antiretroviral Therapy ◽  
Hiv Treatment ◽  
Virologic Suppression ◽  
Social Barriers ◽  
Treatment And Prevention ◽  
Undetectable Viremia ◽  
Long Acting ◽  
Available Information ◽  
Living With Hiv

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community and HIV providers are very interested in exploring the role of long-acting therapies to address some types of barriers to medication adherence. This review summarizes available information about the potential for long-acting therapy to improve adherence for some patients and outlines associated opportunities and challenges with the implementation of long-acting therapy for the treatment and prevention of HIV.

scholarly journals IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9

2013 ◽  
Vol 20 (5) ◽  
pp. 677-689 ◽  
Author(s):  
Holger H H Erb ◽  
Regina V Langlechner ◽  
Patrizia L Moser ◽  
Florian Handle ◽  
Tineke Casneuf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Tissue Expression ◽  
Type I ◽  
Regulatory Factor ◽  
Quantitative Real Time Pcr ◽  
Antiproliferative Effects ◽  
Protein Levels

Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.

scholarly journals SimpactCyan 1.0: An Open-source Simulator for Individual-Based Models in HIV Epidemiology with R and Python Interfaces

2018 ◽  
Author(s):  
Jori Liesenborgs ◽  
Diana M Hendrickx ◽  
Elise Kuylen ◽  
David Niyukuri ◽  
Niel Hens ◽  
...  
Keyword(s):  
Open Source ◽  
Hiv Infections ◽  
Hiv Treatment ◽  
Model Parameters ◽  
Eligibility Criteria ◽  
Hiv Epidemiology ◽  
Treatment And Prevention ◽  
Individual Based Models ◽  
Prevention Programmes ◽  
The Impact

ABSTRACTSimpactCyan is an open-source simulator for individual-based models in HIV epidemiology. Its core algorithm is written in C++ for computational efficiency, while the R and Python interfaces aim to make the tool accessible to the fast-growing community of R and Python users. Transmission, treatment and prevention of HIV infections in dynamic sexual networks are simulated by discrete events. A generic “intervention” event allows model parameters to be changed over time, and can be used to model medical and behavioural HIV prevention programmes. First, we describe a more efficient variant of the modified Next Reaction Method that drives our continuous-time simulator. Next, we outline key built-in features and assumptions of individual-based models formulated in SimpactCyan, and provide code snippets for how to formulate, execute and analyse models in SimpactCyan through its R and Python interfaces. Lastly, we give two examples of applications in HIV epidemiology: the first demonstrates how the software can be used to estimate the impact of progressive changes to the eligibility criteria for HIV treatment on HIV incidence. The second example illustrates the use of SimpactCyan as a data-generating tool for assessing the performance of a phylodynamic inference framework.

Sign in / Sign up

Export Citation Format

Share Document