This document summarizes advances in HIV treatment including HAART and its complications. It discusses how HAART effectively suppresses HIV but can have toxicities over the long term such as body changes, metabolic abnormalities, and liver or bone complications. Adherence is critical for treatment success. Resistance testing helps address treatment failure and resistance. New drugs and strategies continue to be developed and treatment interruption remains experimental. Management requires weighing risks and benefits of therapy changes and treatment goals.
HIV AIDS is one of the most dreadful of all diseases. Newer drugs and drug combination are coming quite frequently. Attempts to design an HIV vaccine is also underway.
This seminar is my attempt this interesting topic with all the latest data I could collect on the internet.
The bacteria that cause tuberculosis (TB) can develop resistance to the antimicrobial drugs used to cure the disease. Multidrug-resistant TB (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs.
The 2 reasons why multidrug resistance continues to emerge and spread are mismanagement of TB treatment and person-to-person transmission. Most people with TB are cured by a strictly followed, 6-month drug regimen that is provided to patients with support and supervision. Inappropriate or incorrect use of antimicrobial drugs, or use of ineffective formulations of drugs (such as use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals.
In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited and expensive, recommended medicines are not always available, and patients experience many adverse effects from the drugs. In some cases even more severe drug-resistant TB may develop. Extensively drug-resistant TB, XDR-TB, is a form of multidrug-resistant TB with additional resistance to more anti-TB drugs that therefore responds to even fewer available medicines. It has been reported in 117 countries worldwide.
Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs or detect resistance patterns. These tests can be molecular in type (such as Xpert MTB/RIF) or else culture-based. Molecular techniques can provide results within hours and have been successfully implemented even in low resource settings.
New WHO recommendations aim to speed up detection and improve treatment outcomes for MDR-TB through use of a novel rapid diagnostic test and a shorter, cheaper treatment regimen. At less than US$ 1000 per patient, the new treatment regimen can be completed in 9–12 months. Not only is it less expensive than current regimens, but it is also expected to improve outcomes and potentially decrease deaths due to better adherence to treatment and reduced loss to follow-up.
Solutions to control drug-resistant TB are to:
cure the TB patient the first time around
provide access to diagnosis
ensure adequate infection control in facilities where patients are treated
ensure the appropriate use of recommended second-line drugs.
In 2015, an estimated 480 000 people worldwide developed MDR-TB, and an additional 100 000 people with rifampicin-resistant TB were also newly eligible for MDR-TB treatment. India, China, and the Russian Federation accounted for 45% of the 580 000 cases. It is estimated that about 9.5% of these cases were XDR-TB.
TB remains an important disease condition globally, particularly with the high prevalence of HIV in many parts of the world. While there is interest in providing the adequate and often readily-available treatment, it might do more harm to the patient. In this presentation, I explored the concept of IRIS in the management of tuberculosis.
adult vaccination, types of vaccine, forms of vaccine, active immunity, passive immunity, schedule of vaccination, CDC, contraindications, cost of vaccines
HIV AIDS is one of the most dreadful of all diseases. Newer drugs and drug combination are coming quite frequently. Attempts to design an HIV vaccine is also underway.
This seminar is my attempt this interesting topic with all the latest data I could collect on the internet.
The bacteria that cause tuberculosis (TB) can develop resistance to the antimicrobial drugs used to cure the disease. Multidrug-resistant TB (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs.
The 2 reasons why multidrug resistance continues to emerge and spread are mismanagement of TB treatment and person-to-person transmission. Most people with TB are cured by a strictly followed, 6-month drug regimen that is provided to patients with support and supervision. Inappropriate or incorrect use of antimicrobial drugs, or use of ineffective formulations of drugs (such as use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals.
In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited and expensive, recommended medicines are not always available, and patients experience many adverse effects from the drugs. In some cases even more severe drug-resistant TB may develop. Extensively drug-resistant TB, XDR-TB, is a form of multidrug-resistant TB with additional resistance to more anti-TB drugs that therefore responds to even fewer available medicines. It has been reported in 117 countries worldwide.
Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs or detect resistance patterns. These tests can be molecular in type (such as Xpert MTB/RIF) or else culture-based. Molecular techniques can provide results within hours and have been successfully implemented even in low resource settings.
New WHO recommendations aim to speed up detection and improve treatment outcomes for MDR-TB through use of a novel rapid diagnostic test and a shorter, cheaper treatment regimen. At less than US$ 1000 per patient, the new treatment regimen can be completed in 9–12 months. Not only is it less expensive than current regimens, but it is also expected to improve outcomes and potentially decrease deaths due to better adherence to treatment and reduced loss to follow-up.
Solutions to control drug-resistant TB are to:
cure the TB patient the first time around
provide access to diagnosis
ensure adequate infection control in facilities where patients are treated
ensure the appropriate use of recommended second-line drugs.
In 2015, an estimated 480 000 people worldwide developed MDR-TB, and an additional 100 000 people with rifampicin-resistant TB were also newly eligible for MDR-TB treatment. India, China, and the Russian Federation accounted for 45% of the 580 000 cases. It is estimated that about 9.5% of these cases were XDR-TB.
TB remains an important disease condition globally, particularly with the high prevalence of HIV in many parts of the world. While there is interest in providing the adequate and often readily-available treatment, it might do more harm to the patient. In this presentation, I explored the concept of IRIS in the management of tuberculosis.
adult vaccination, types of vaccine, forms of vaccine, active immunity, passive immunity, schedule of vaccination, CDC, contraindications, cost of vaccines
This is an informative, illustrated presentation about the causes, symptoms, treatment and prevention of HIV AIDS. Gives relevant data, facts and statistics about the disease updated to the most recent 2010 data.
HIV infection
Mode of transmission, pathogenesis, clinical manifestations, laboratory diagnosis, treatment, prevention, prognosis, scope of AIDS vaccine.
Aptamers provide opportunities for structure-based drug design strategies relevant to therapeutic intervention. Recent advances in the chemical modifications of nucleic acids suggest that one of the major barriers to use, stability, can be overcome. The high affinity and specificity of aptamers rival antibodies and make them a promising tool in diagnostic and therapeutic application. We should expect more aptamers to be isolated in the near future against an ever increasing repertoire of targets, using these different SELEX approaches with increased speed and efficiency. Aptamers are poised to successfully compete with monoclonal Abs in therapeutics and drug development within the next few decades.
Hepatitis And Hiv Co Infection Tonia Poteat 060508elfaye
A presentation by Tonia Poteat from the CDC Global AIDS Project on the topic of Hepatitis B & C and HIV Co-infection. This webcast was presented live to ECHO (Evaluation Center for HIV and Oral Health) grantees on June 5, 2008.
ARV Therapy and the Role of Early Intervention presented by Dr. Rachel Baden, Harvard Medical Faculty Physician at the Fenway Health Center community education conference: An End To AIDS - How A State Bill Can Change Everything hosted by SearchForACure.org, the Fenway Health Center, and the MA Dept. of Public Health
Современное лечение ВИЧ: лечение ВИЧ у пациентов с вирусными гепатитами.Conte...hivlifeinfo
Современное лечение ВИЧ: лечение ВИЧ у пациентов с вирусными гепатитами.Contemporary Management of HIV. Managing HIV in Viral Hepatitis Coinfection.2016
In this downloadable slideset, David L. Wyles, MD, and Program Director Eric S. Daar, MD, review key data and optimal approaches for ART management in patients with HIV and viral hepatitis coinfection.
Format: Microsoft PowerPoint (.ppt)
File size: 1.85 MB
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
Advances in hiv treatment
1. Advances In HIV Treatment:
HAART And Its Complications
Amy V. Kindrick, M.D., M.P.H.
National HIV/AIDS Clinicians’
Consultation Center
April 26, 2003
2. Overview
New concepts and strategies in HIV
antiretroviral therapy
Long-term toxicities of ARV therapy
New and investigational ARV agents
New strategies for OI management
Common management challenges
11. What’s a Clinician to Do?
Expanding number
of agents adds
complexity
Minimal clinical
experience when
drugs released adds
toxicity risk
Shortage of
outcomes data adds
uncertainty
12. New ARV Treatment
Strategies and Concepts
Adherence to treatment
ARV resistance and resistance testing
Interrupting ARV therapy
Treating primary HIV infection
14. Reasons for Non-Adherence:
Clinician vs Patient Views
0
10
20
30
40
50
60
value,%
No. of doses or
pills
Side Effects Meal Instructions Schedule
complexity
Other
Clinican
Patient
Chesney M. Adherence to antiretroviral therapy. 12th World AIDS Conference, 1998; Geneva. Lecture 281
15. Viral Suppression And
Adherence By Refill Records
0
10
20
30
40
50
60
70
80
90
95-100% 90-95% 80-90% 70-80% < 70%
Adherence, by prescription refill
%Achieving<500copies/mL
N = 504 pts on HAART
Montessori, V, et al. XII International Conference on AIDS, Durban, South Africa, 2000. Abstract MoPpD1056.
17. 0
20
40
60
80
100
>95 90-95 80–90 70-80 <70
PatientswithHIVRNA
<400copies/mL,%
PI adherence, % (electronic bottle caps)
Paterson, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago, IL. Abstract 92.
Viral Suppression And
Adherence By MEMS
18. 10% adherence difference = 21% reduction in risk of AIDS
Bangsberg D, et al. AIDS. 2001:15:1181
ProportionAIDS-Free
Months from entry
P = .0012
0 5 10 15 20 25 30
0.00
0.25
0.50
0.75
1.00
Adherence
O 90–100%
O 50–89%
O 0–49%
Adherence and AIDS-Free Survival
24. How Does Resistance
Develop?
High replication and transcription error rates
generate mutant HIV variants
Spontaneously generated variants often
contain mutations that confer survival
advantage in the presence of antiretroviral
agents
Poor adherence or suboptimal regimens can
lead to resistance and ‘viral breakthrough’
25. HIV-1 Quasi Species in Untreated
and Treated HIV Infection:
Heterogeneity vs. Selection of Resistant Strains
acute chronic AIDS
Time
V. Simon, MD
Plasmaviremia
31. Definitions
Genotype
Virus nucleotide sequence from which a protein’s
amino acids can be deduced
Mutations reported as change in the deduced amino acid
sequence, e.g., Met184Val
Specific mutations confer phenotypic resistance
The phenotype is always derived from the genotype
Phenotype
Relative growth of the virus in the presence
of different drug concentrations
Usually reported as the drug concentration that inhibits
virus replication by 50% (IC50), or the fold increase in
IC50
32. Genotype Vs Phenotype
Availability
Turnaround time 2 weeks
Mutations may precede
phenotypic resistance
Lower cost
GENOTYPE
Requires expert interpretation
Measures susceptibility indirectly
Insensitive for detecting minor species
Does not assess interactions among
mutations
Does not address drug levels
Measures susceptibility
directly
Results are easier to
interpret
PHENOTYPE
Restricted availability
Turnaround time 2–4 weeks
Insensitive for detecting minor species
Clinically significant cutoff values may
not be defined for some drugs
More expensive
Fast results (2 weeks)
Moderate cost
VIRTUAL
PHENOTYPE
Measures susceptibility indirectly
Insensitive for detecting interactions
between mutations
Strengths Weaknesses
33. HIV Drug Resistance Assays:
DHHS Recommendations
Clinical Situation Recommendation/Rationale
Virologic failure during ART
Determine role of resistance in failure
or suboptimal viral suppression
Maximize number of active drugs
Acute HIV infection
Assess possibility of drug-resistant
HIV transmission
Treat accordingly
Chronic HIV infection prior to
treatment initiation
After D/C ART
Plasma HIV RNA <1000 copies/mL
Uncertain prevalence of resistant
virus/assays may not detect minor
quasispecies
Assays may not detect certain quasi-
species in the absence of selective
pressure
HIV RNA too low for reliable
detection with current assays
RecommendedOptionalNotGenerallyRecommended
36. Long-Term Complications of
HIV and ARV Therapy
Body habitus changes
Insulin resistance/hyperglycemia/diabetes
Hyperlipidemia
Lactic acidosis
Hepatic steatosis
Osteopenia
Avascular necrosis
37. Abnormal Fat Redistribution
Syndromes
Abnormal fat accumulation
Buffalo hump
Increased abdominal girth
Increased breast size
Peripheral fat wasting
“Sunken cheeks”
Thin extremities
Prominent peripheral musculature and veins
Prevalence unknown (est. 2% to 80%)
Increased with duration of HIV infection & ARV tx
Associated with PI and NRTI use
Mechanism unknown
43. Abnormal Insulin and Glucose
Metabolism
Associated with ARVs, especially PIs
Mechanism unclear
?PI inhibition of glut-4 transporter
Risk factors
Older age
African American ethnicity
Clinical syndromes
Insulin resistance
Hyperglycemia
Type 2 diabetes
Treat as usual
45. Hyperlipidemia Treatment
Considerations
Risk of increased insulin resistance with
niacin
Increased risk of myopathy and
rhabdomyolysis
Interactions between ARVs and statins
Prefer pravastatin or atorvastatin
Avoid lovastatin and simvastatin
Interactions between statins and fibrates
May respond to ARV change
46. Lactic Acidosis And Hepatic
Steatosis
Class toxicity of NRTIs (Black Box
warning)
Incidence est. 4/1000 patient-years
Risk factors
Older age
Female gender
ddI, ddC, or d4T use > 3 months
ddI+d4T in pregnancy
48. Management Of Lactic
Acidosis
Be alert to symptoms
Stop ARVs if symptomatic and lactate
elevated
May consider continuing ARVs if
Symptoms absent or mild
Lactate only minimally elevated (e.g., 2-4 mmol/l)
ddI, d4T can be replaced
Anecdotal treatments for mild disease
L-carnitine
Riboflavin
Thiamine
49. Delayed Onset NRTI Toxicity
Hypothesized due to toxic effects of NRTIs on
human mitochondria
NRTIs inhibit DNA polymerase γ required for
mDNA synthesis
Clinical syndromes
Pancreatitis
Myopathy
Peripheral neuropathy
Bone marrow toxicity
“D” drugs especially implicated
52. Changing Therapy:
Considerations
Recent clinical
history and physical
examination
Two plasma HIV
RNA levels
CD4+ T cell count
Remaining
treatment options
Drug failure or drug
toxicity?
Medication
adherence
Pharmacology &
drug interactions
Resistance profile
Patient preference
53. Should “Failing” HAART Be
Stopped?
Better to stay on some ARV regimen
than none
Resistance mutations may impair viral
“fitness”
Specific mutations may enhance response
to specific ARV agents
CD4 count gains may be sustained despite
incomplete viral suppression
Deeks, et al. NEJM 2/15/01
57. Treatment Interruption Target
Groups
ARV treatment fully suppressive
Started during acute infection
Started after infection chronic
ARV treatment not fully suppressive
66. ARV Therapy for Primary
Infection
Pros
May prevent immune
system damage
May allow control of
viremia without
ARVs
Cons
No obvious end point
Risk of cumulative
ARV toxicity
Risk of suboptimal
adherence leading to
emergence of
resistance
70. Common Management
Challenges
Coinfection with viral hepatitis
More rapid hepatitis progression
Increased risk of ARV-associated hepatotoxicity
Increased risk of toxicity associated with hepatitis
treatment
Pregnancy
Tolerability
Teratogenicity
Metabolic toxicity
Transmission
71. Resources for HIV/AIDS
Clinicians
Handbooks
Sanford Guide to HIV/AIDS Therapy
The Medical Management of HIV Infection
Internet
HIV InSite (http://hivinsite.ucsf.edu)
Medscape (www.medscape.com)
HIV/AIDS Treatment Information Service
(www.hivatis.org)
Johns Hopkins (www.hopkins-aids.edu)
National HIV/AIDS Clinicians’ Consultation Center
(www.ucsf.edu/hivcntr)
72. Consultation Services For
HIV/AIDS Clinicians
Local expert clinicians
Regional and local AIDS Education and
Training Centers
National HIV Telephone Consultation Service
(Warmline)
(800) 933-3413
National Clinicians’ Post-Exposure
Prophylaxis Hotline (PEPline)
(888) HIV-4911
73. National HIV/AIDS Clinicians’
Consultation Center
A Joint Program of UCSF
and San Francisco General Hospital
Supported by HRSA and CDC
http://www.ucsf.edu/hivcntr
Akindrick@nccc.ucsf.edu
PEPLine (888) 448-4911
Warmline (800) 933-3413
Editor's Notes
Not Over
Date of first publication: 2/1/99 Keywords: Adherence, antiretroviral therapy, viral load Subject: Degree of adherence needed for optimal viral suppression Title: “What degree of adherence is needed?” Discussion and teaching points: How much adherence is needed for optimal viral load suppression is addressed in the graph from Paterson which shows that the best performance was achieved in patients who by self-report and MEMS-caps were found to have >95% adherence, I.e. Better than 95% of doses were taken during the 3 months of study. Sig- nificant differences were observed between >95%, 90-95%, 80-90%, 70-80%, and <70% adherence, as shown. Note that <70% adherence was associated with only 10% of patients achieving a viral load below detection. Author(s): Paterson et al. Sources: University of Pittsburgh Sponsors: NA
Currently, there are three commonly used resistance analyses: 1) determination of the viral genotype; 2) assessment of the viral phenotype in vitro; and 3) determination of a "virtual" phenotype based on genotypic assessment. Each of the three above-listed approaches has distinct strengths and weaknesses. Assessments based on determination of the viral genotype are readily available, provide relatively rapid results, and have low to moderate cost. Knowing the viral genotype may also permit prediction of future phenotypic resistance. Weaknesses of these approaches include requirement for expert interpretation, and the facts that they only indirectly measure resistance, do not take into account interactions among mutations, and do not include information about antiretroviral drug levels. Phenotypic resistance analysis measures susceptibility directly, and thus results are relatively easy to interpret. However, phenotypic testing is expensive and not widely available. In addition, its turnaround time is relatively long, it is insensitive to minor species, and clinically significant cutoff values may not be established for all drugs.
Considerations for Changing a Failing Regimen As with the initiation of antiretroviral therapy, the decision to change regimens should be approached with careful consideration of several complex factors. These factors include: recent clinical history and physical examination; plasma HIV RNA levels measured on two separate occasions; absolute CD4+ T lymphocyte count and changes in these counts; remaining treatment options in terms of potency, potential resistance patterns from prior antiretroviral therapies and potential for compliance/tolerance; assessment of adherence to medications; and preparation of the patient for the implications of the new regimen which include side effects, drug interactions, dietary requirements and possible need to alter concomitant medications. Failure of a regimen may occur for many reasons, including initial viral resistance to one or more agents, altered absorption or metabolism of the drug, multi-drug pharmacokinetics that adversely affects therapeutic drug levels, and poor patient adherence to a regimen. In this regard, it is important to carefully assess patient adherence prior to changing antiretroviral therapy; health care workers involved in the care of the patient, such as the case manager or social worker, may be of assistance in this evaluation. Clinicians should be aware of the prevalence of mental health disorders and psychoactive substance use disorders in certain HIV-infected persons; inadequate mental health treatment services may jeopardize the ability of such individuals to adhere to their medical treatment. Proper identification of and intervention in these mental health disorders can greatly enhance adherence to medical HIV treatment. It is important to distinguish between the need to change therapy due to drug failure versus drug toxicity. In the latter case, it is appropriate to substitute one or more alternative drugs of the same potency and from the same class of agents as the agent suspected to be causing the toxicity. In the case of drug failure where more than one drug had been used, a detailed history of current and past antiretroviral medications, as well as other HIV-related medications, should be obtained. Testing for antiretroviral drug resistance may also be very helpful in maximizing the number of active drugs in a regimen (see Testing ). Viral resistance to antiretroviral drugs is an important, but not the only, reason for treatment failure. Genetically distinct viral variants emerge in each HIV-infected individual over time after initial infection. Viruses with single drug resistant mutations exist even prior to therapy, but are selected for replication by antiviral regimens that are only partially suppressive. The more potent a regimen is in durably suppressing HIV replication, the less likely the emergence of resistant variants. Thus the goal of therapy should be to reduce plasma HIV RNA to below detectable limits using the most sensitive assay available (<50 copies/mL), thereby providing the strongest genetic barrier possible to the emergence of resistance.
As everyone here knows, state of the art HIV therapy changes at lightning speed. Much of antiretroviral treatment of HIV infected is guided by outcome based studies. The story is different for post-exposure prophylaxis. Most of what we know about how to provide PEP comes from the original case control study of HCWs, anecdotes, animal data, and perinatal prophylaxis studies. Because infection is a rare event, thankfully, there is very little outcome data. This is striking contrast to the information available how to use antiretroviral therapy as treatment, as opposed to prevention where there is an relative abundence of outcome data. Many clinicians have tried to bridge this gap by extrapolating treatment data to prevention strategies. Thus, the rapid changes in antiretroviral use as treatment leads to rapid changes in antretroviral use as prevention. As a result, PEP in practice is likely to move quite rapidly. However the biology as well as the risk-benefit decision is quite different between treatment and prevention. Not all extrapolations from treatment data to prevention strategies may or may not be rational. As a result PEP in practice is likely to be different that PEP guidelines. What I would like to do today is to describe PEP in practice. I will focus mostly on PEP treatment decisions which have not been addressed by the quidelines.