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Dr Shay Ganesh, Clinical Manager at medical Research Council in the HIV Prevention, Treatment and Wellness Unit presented on local and global HIV prevention efforts, focusing on previous, current and future programmes. Dr Ganesh looked towards Pre-Exposure Prophylaxis as a possible future prevention programme and gave some insight into possible programmatic and public health challenges involved in rolling out new HIV prevention programmes.
Zika Virus Surveillance and Reporting in the CaribbeanUWI_Markcomm
Shaping the Caribbean's response to Zika, UWI’s Zika Task Force (www.uwi.edu/zika) is gathering and providing expert advice and developing a strategic, scientific approach to tackling the Zika virus.
Biosecurity issues impact on key crops and environmental values across NZ and Australia. A key outcome for the project team will be the ability of indigenous communities, and relevant regulatory authorities and industries, to better manage the social, environmental and economic impacts of biosecurity threats, and to participate in biosecurity strategies through improved bicultural engagement models that build empowerment and ownership in indigenous communities and their response to those threats. The teams have developed an engagement model adapted to the indigenous peoples and their communities of each country.
MRC/info4africa KZN Community Forum | May 2012info4africa
Dr Shay Ganesh, Clinical Manager at medical Research Council in the HIV Prevention, Treatment and Wellness Unit presented on local and global HIV prevention efforts, focusing on previous, current and future programmes. Dr Ganesh looked towards Pre-Exposure Prophylaxis as a possible future prevention programme and gave some insight into possible programmatic and public health challenges involved in rolling out new HIV prevention programmes.
Zika Virus Surveillance and Reporting in the CaribbeanUWI_Markcomm
Shaping the Caribbean's response to Zika, UWI’s Zika Task Force (www.uwi.edu/zika) is gathering and providing expert advice and developing a strategic, scientific approach to tackling the Zika virus.
Biosecurity issues impact on key crops and environmental values across NZ and Australia. A key outcome for the project team will be the ability of indigenous communities, and relevant regulatory authorities and industries, to better manage the social, environmental and economic impacts of biosecurity threats, and to participate in biosecurity strategies through improved bicultural engagement models that build empowerment and ownership in indigenous communities and their response to those threats. The teams have developed an engagement model adapted to the indigenous peoples and their communities of each country.
A comprehensive and detailed guide to Seo Footprints. Learn about the proven method to find and use SEO Footprints to help rank better in Search Engine like Google and Bing. If you know how to find Seo footprints, then you have hit the goldmine and building backlinks become so much easier.
The Australia-Africa Plant Biosecurity Partnership has brought together plant biosecurity professionals in ten African countries and established linkages with Australian researchers, helping
to reduce pest and disease impacts in sub-Saharan Africa. At the outset of this initiative, diagnostic skills were identified as a priority area in connecting Australian expertise with Africa and improving surveillance capability, post-entry quarantine, early warning and phytosanitary certification. This presentation will briefly examine the application of improved diagnostic skills in African Plant Protection Organisations and the longer term relationships that have been established with Australian mentors.
PATH Malaria Vaccine Initiative's (MVI) presentation at the 2009 Partnering for Cures meeting in New York. MVI's mission is to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world.
Dec 11, '14 WEBINAR - Lubes, Rings, Films, Fibers, and Shots 4 HIV PreventionJim Pickett
Project RSP+ Webinar - December 11, 2014. Presentation explores the pipeline of new HIV prevention technologies in the research and development phase. This project is an initiative of the AIDS Foundation of Chicago.
A comprehensive and detailed guide to Seo Footprints. Learn about the proven method to find and use SEO Footprints to help rank better in Search Engine like Google and Bing. If you know how to find Seo footprints, then you have hit the goldmine and building backlinks become so much easier.
The Australia-Africa Plant Biosecurity Partnership has brought together plant biosecurity professionals in ten African countries and established linkages with Australian researchers, helping
to reduce pest and disease impacts in sub-Saharan Africa. At the outset of this initiative, diagnostic skills were identified as a priority area in connecting Australian expertise with Africa and improving surveillance capability, post-entry quarantine, early warning and phytosanitary certification. This presentation will briefly examine the application of improved diagnostic skills in African Plant Protection Organisations and the longer term relationships that have been established with Australian mentors.
PATH Malaria Vaccine Initiative's (MVI) presentation at the 2009 Partnering for Cures meeting in New York. MVI's mission is to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world.
Dec 11, '14 WEBINAR - Lubes, Rings, Films, Fibers, and Shots 4 HIV PreventionJim Pickett
Project RSP+ Webinar - December 11, 2014. Presentation explores the pipeline of new HIV prevention technologies in the research and development phase. This project is an initiative of the AIDS Foundation of Chicago.
You Geaux Girl! Internet based Pregnancy Prevention in New OrleansYTH
Jakevia Green at Tulane University presented the results of a clinical trial of the BUtiful program - Be yoU! Talented Informed Fearless Uncompromised and Loved- a social media pregnancy prevention program for New Orleans women.
Similar to Microbicides: A New Hope for HIV/STIs. Global and Local Perspectives (20)
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The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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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
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
2. The Global Impact of HIV
People living with
HIV in 2006
New infections in
2006
Worldwide 39.5 million 4.3 million
Sub-Saharan Africa 24.7 million 2.8 million
Asia & Eastern Europe 10.25 million 1.23 million
North America &
Western/Central Europe 2.14 million 65,000
Other 2.49 million 242,100
Women are disproportionately affected by AIDS:
In Sub-Saharan Africa, young women are 4 times
more likely to be infected than young men.
3.
4.
5. Why We Need Female Controlled Methods
Biology
–Women are 2-4 times more likely than men
to get HIV from unprotected
sex
Economics
–Economic need or dependency
–Less able to assert their rights
Social & Cultural
–Gender norms about sexuality
–Gender based violence
Current methods (abstinence, fidelity, and
condom use) often require male consent,
participation & cooperation
6. Protection in Primary Partnerships:
Difficult to Achieve
• People generally are willing to to use
condoms with new partners, or
during casual or commercial sex
• But once “trust” enters the equation
the condom comes off
• Sex with a primary partner is the
biggest source of HIV infection
among women globally
8. What Do We Need from Microbicides?
•To be contraceptive and non-contraceptive
•To reduce risk of other STIs
•To be safe and non-irritating
•To be inexpensive and available over the
counter
•To be possibly used without partner’s
cooperation or even awareness
9. How could microbicides work?
• Kill/inactivate/immobilize the virus
• Boost body’s natural defenses
• Prohibit viral entry by blocking fusion
• Inhibit viral replication
• Create a physical barrier
or some combination of these approaches
10. 2.
surfactants
3. entry inhibitors =
CS, Carraguard,
Pro2000
4. anti-retrovirals
=Tenofovir, UC781,
TMC120
1. boosts vagina’s
natural defenses -
Buffergel
Source: Shattock, R.; Moore, J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol 1, October 2003.
12. 3 Products Furthest Along
Product
Trial sponsor
# women to be
enrolled Location
Preliminary
results expected
in
Buffer Gel
HPTN035-NIH
3,100 women South Africa, Malawi,
Tanzania, Zambia,
Zimbabwe and
Philadelphia
April 2009
Carraguard
Population Council
6,299 women South Africa – 3 locations December 2007
PRO2000 (.5%)
HPTN035-NIH
3,100 women South Africa, Malawi,
Zambia, Zimbabwe and
Philadelphia
April 2009
PRO2000
(.5 and 2%)
DFID, MRC
9,673 women South Africa, Uganda,
Zambia, Tanzania
December 2009
14. How Effective Will Microbicides Be?
First microbicides may be 40-60% protective
Second generation may be 60-80%
Promoted as a back-up to condoms, not as a
replacement.
“Use a microbicide with your condom for added
pleasure and protection.”
“Use a male or female condom every time you have
sex; if you absolutely can’t use a condom, use a
microbicide.”
15. Potential Public Health Impact
If a 60% effective product
Offered to 73 lower income countries
Is used by 20% people reached by health care
during 50% of unprotected sex acts
= 2.5 million HIV infections averted
in 3 years including women, men and children
16. Laboratory
Testing
2-6 Years
Phase III
(efficacy)
2 to 4
Years
Simultaneous studies in some cases:
HIV+, penile & rectal safety
10 or more years
3 products
3 products
4 products
30+ products
Phase I
(safety)
1 to 6
Months
Phase II
(safety)
Up to 2
Years
25 – 40
people
200-400
people
3,000-10,000
people
The Product Pipeline in 2007
Source: Alliance Pipeline Update, first week of every month - http://www.microbicide.org/publications
17. Clinical Trial Sites in 2007
AUSTRALIA
- Phase 1
WEST AFRICA:
-Cameroon: Phase I, II
THE AMERICAS:
-United States: Phase I, II, IIB
-Brazil: Phase II
SUB-SAHARAN AFRICA:
-Botswana:
-Kenya: planned
-Madagascar: Phase
-Malawi: Phase II, IIB
-Rwanda: Phase I/II
-South Africa: Phase I, IIB, III
-Tanzania: Phase III
-Uganda: Phase III
-Zambia: Phase IIB, III
-Zimbabwe: Phase I, II, IIB
ASIA
-India: Phase II
-Thailand: Phase I
Source: Alliance for Microbicide
Development
EUROPE
- Belgium: Phase I/II
18. When can we expect a microbicide?
•Earliest results from current Phase 3
trials in 2008-2009
•If shown to be effective, a microbicide
may be available in a few countries via
introductory studies in the next 5 years
• If not, we will have to wait
for results from second
generation products
19.
20. The Microbicide Trials Network (MTN) is a worldwide
collaborative clinical trials network that evaluates the
safety and efficacy of microbicides designed to prevent
HIV transmission and will support licensure of topical
microbicide products.
The MTN plans to develop and/or execute 15 separate
clinical trials of microbicides between 2006 and 2013.
Network led by Sharon Hillier at Magee Women’s Health
Foundation/U Pitts: Dr. Ian McGowan is a Co-principal
investigator.
PMG – Chair of Behavioral Research Committee
21. Topics on BRC Scientific Agenda:
Adherence & Acceptability
Topic Measurement
Context Measurement approaches for
contexts of microbicide use
Partners Partner types and relationship
dynamics
Microbicide Administration Methods
Biomarkers Use of biomarkers for
comparison with or validation of
behavioral measures of
adherence
Pregnancy Pregnancy intentions at
screening, affects of trial
participation at individual and
community level
22.
23.
24.
25. Experience of a
Phase III Participant
Recruitment:
Participant
receives
information
about the trial
in their own
language
Screening Visit
1: Education about
the trial, HIV and
pregnancy test, STI
tests and
treatment, baseline
data collected
Screening Visit
2: Results of tests,
counselling,
reinforce education
about trial
Randomisation
: Participant
assigned by
chance to a
group.
Family
Planning
Informed
consent for
screening
Informed
consent
to enroll.
Condoms
+ placebo
Condoms +
experimental
gel
26. Handheld screen with 035
adherence question (n=400 in
Malawi
Courtesy of Barbara Mensch, Population Council
27. Malawi – Pop Council School
Study
Courtesy of Barbara Mensch, Population Council
28. Microbicide Research in
LA
• Focus on rectal microbicide development
• Principle research effort led by UCLA:
– Microbicide Development Program (MDP) –
U19 funded by NIAID
• Preparedness:
– NARLA: Project 2 -
29. Rectal Microbicides
• Many people (women
and men) need
microbicides for anal
intercourse
• Creating an effective
rectal microbicide is
scientifically more
complicated
• Vaginal microbicides
must be accurately
labeled
Photo courtesy of www.lifelube.org
30. •PI: Peter Anton & Ian McGowan. Collaborative effort with
NIH and industry to initiate multidisciplinary research on
rectal microbicides through multiple projects including:
Preclinical Evaluation of HIV Rectal Microbicides
Rectal Health, Behaviors and Product Acceptability
Phase I trial of a rectal microbicide UC-781 a reverse
transcriptase (RT) microbicide
•These studies are designed to help develop a product
that people will find acceptable and actually use.
Findings will help guide the selection of the
formulation used in human trials.
31. Two Components:
(1) Integrated behavioral
and clinical study of
receptive anal
intercourse
(2) Applicator method
acceptability
(preference) study
• 2 sites: LA, Baltimore
Rectal Health, Behaviors and Microbicide
Acceptability – U19 Project 3 - Gorbach
32. “AMP” Ano-rectal Microbicide Project
896 participants
½ in LA
½ men & ½ women
½ HIV positive
½ report recent RAI
All complete:
STI/HIV testing
HRA
Clinical exam
Behavioral
Questionnaire
Already ~ 219 studied!
33.
34. Why This Study?
Preparedness…
• Rectal microbicides are in development.
• The public knows little about rectal microbicides.
• There will soon be clinical trials of rectal
microbicides that will need participation from
those who need and will use them. A Phase I trial
started in LA (U19).
• There is a need for specially designed materials to
introduce the public to rectal microbicides (both
within clinical trials and beyond) to optimize their
value as a method of HIV prevention.
• Preliminary work with communities is necessary to
prevent misinformation and enhance acceptability.
35. Study Goals
1. Assess the best format
to deliver educational
materials about rectal
microbicides to
potential participants
in clinical trials, and
2. Consider potential
barriers to microbicide
trial participation by
analyzing factors that
facilitate enrollment
and retention in a
microbicide trial
registry in a cohort of
men in Los Angeles
N=>106 already!
Total cohort 450 men
37. What if microbicides don’t work?
• Build on the lessons in development of new
technologies – process is iterative.
• But….keep perspective. Failure of one product that
utilizes one mechanism of action in microbicide
does not mean all microbicides are doomed. Many
other products and other mechanisms in the
pipeline
• Future microbicide will likely use combination
mechanisms and will likely include coitally & non-
coitally dependent methods
• Setbacks may happen but science must move
forward – there is an epidemic…
38. Imagine a Full Spectrum of Interventions
Prior to exposure Point of transmission Treatment
•Male and female
condoms and lube
•PMTCT
•Clean injecting
equipment
•Vaginal and rectal
microbicides
•Cervical barriers
•PEP
•Anti-retroviral treatment
•Treatment for
opportunistic infections
•Basic care/nutrition
•Prevention for positives
•Education and behavior
change
•Therapeutic
vaccines
•Rights-focused
behaviour change
•VCT
•STI screening and
treatment
•Preventative
Vaccines
•PREP
•Male
circumcision
39. FrankHerholdt,CourtesyofMicrobicideDevelopmentProject
•The global and local need for
microbicides is urgent as
women and men continue to
become infected and suffer
from HIV
•There are vaginal & rectal
microbicides in clinical trials
now
•Microbicides offer great
potential to impact HIV
epidemics –one more
prevention tool - self not
partner controlled
Editor's Notes
[Please start off by introducing yourself and your organization. Say why you are making this presentation and why this issue is important to you. You may want to say that you are doing this presentation on behalf of the Global Campaign for Microbicides which is a coalition of 250 non-profit organizations that advocate for new HIV prevention options. The Global Campaign does not sponsor trials or do the research. Then you could say something like:] Microbicides are products that have the potential to transform the HIV prevention landscape by giving us a new method of protection that is user-initiated, instead of partner initiated. I think it is clear to all of us that not everyone has the power in their relationships to insist on condom use during every act of intercourse. So we need to start talking about what IS possible for women and men in this situation -- what can be developed that would enable both partners to protect themselves when a condom isn’t being used and add to the effectiveness when condoms are used. Today, I would like to talk about three things: 1) First, I will introduce you to the concept of microbicides and how they might fit into an overall program of HIV prevention; 2) Then, I will talk a little bit about how microbicides are being developed, how they would work and where the research is at right now; Finally, I will talk about why we have to develop a vocal and active constituency for microbicides to make sure that this vital new technology reaches the market as soon as possible. [Note to speaker: References are on the final page of the script for this presentation; You are welcome to add your group’s logo to the home page, and your website to the bottom of each slide]
Even if you don’t work in HIV/AIDS or women’s health, you can tell by reading the newspaper or listening to the news how urgently we need more prevention options to fight the spread of the pandemic around the world and right here at home. The statistics are mind-numbing. 1 AIDS has killed more than 25 million people since it was first recognised in 1981, making it one of the most destructive epidemics in recorded history. 2 More than 14,000 people are newly infected every day, and almost 40 million people are living with HIV today. Sub-Saharan Africa has been the hardest hit region, with rates soaring in other parts of the world as well, particularly in China and India. It is women who are bearing the brunt of the pandemic in Africa, especially young women. In Sub-Saharan Africa, young women are three times more likely to be infected than young men (aged 15-24). 1
Women are at higher risk of HIV infection than men partly because of biology, partly because of economics, and partly because of culture. Women are more vulnerable to HIV because they are exposed to more virus for a longer period of time during sex. 3 Young girls are especially at risk because their reproductive tracts are not fully mature. Economically, in many places, women have less access than men to education, job opportunities, property, or credit, making them financially dependent on their partners. 4 As a result, women often cannot afford to leave relationships that put them at risk of HIV and other STDs. Culture also plays a role. Here and abroad, women are expected to be faithful but men are not. A male partner’s infidelity is one of the greatest HIV risks women face. In addition, gender based violence is a big factor in women’s risk. 5 The current prevention methods (abstinence, fidelity, and condom use) often require active acceptance, participation, consent and cooperation by both partners. But women don’t always have control over when and how they have sex. Although we are making important progress on getting treatment to people, we still need to do everything we can to give people more prevention options especially those that they themselves can control . [Note for some audiences: In this presentation, I am talking mainly in terms of the risk women experience when their male partners won’t use condoms. I realize that all people need tools to protect themselves. For the sake of simplicity, I’m going to just say “women’s risk” here – and ask you to bear in mind that both men and women need more prevention options.]
A little recognized truth is that more women get infected with HIV from their boyfriends and husbands, than from casual or commercial sex. Throughout the world, once trust enters a relationship –- condoms usually exit the scene. With proper condom promotion programs, we can help people use condoms in the context of casual or commercial sex. But few people continue to use condoms once they establish a regular partnership. Even with intense condom promotion efforts, consistent condom use among regular partners is difficult to achieve, unless of course the couple knows that one is infected and one is not. 9 “In representative surveys of women in 13 African countries found that fewer than 7% report condom use in the last sex act with their regular partner.” 9,10 Microbicides could potentially help to fill the gap by offering couples a more intimate option in long-term relationships.
So what is a microbicide? A microbicide is any substance that can substantially reduce the risk of acquiring or transmitting sexually transmitted diseases, including HIV, when it is applied in the vagina or rectum. It’s important to understand that no proven microbicides exist yet on the market. What we’re talking about here are products that are still being researched. The first generation of microbicides could be available on the market in as little as five to seven years. They will probably look a lot like the over-the-counter yeast infection treatments and birth control products we already know -- the gel, foam, cream and suppository-type products that have been on the shelves for years. They won’t contain the same chemicals as these birth control products but they will come in some of the same formulations. But scientists are also working on developing new formulations that may make the second generation of microbicides even more user-friendly than today’s spermicides. For example, they’re working to make formulations that women can use several hours or even days before intercourse, if necessary. One possibility is a vaginal ring or sponge-- something that could slowly release the protective substance over time, providing round the clock protection. Another possibility is combining a physical barrier -- such as a diaphragm or cervical cap -- with a microbicide. Since the cervix is more vulnerable to infection than the vaginal walls, this combination might provide highly effective protection.
Some of the microbicides being developed will also be contraceptive. And that’s great because many women would like to have a product that can protect them from disease and pregnancy at the same time. But scientists are also working on non-contraceptive microbicides that would be helpful to women and men who want to conceive a child while still protecting themselves from possible infection --- something that is impossible with condoms. Some microbicides are also being tested for efficacy against other sexually transmitted infections (STIs), and several of them appear to reduce risk of at least one or two other STIs . Eventually, scientists may be able to combine active ingredients so that one product can serve several purposes. Obviously, we need products that are safe and don’t irritate any tissue or organs. Irritation, inflammation or allergic reaction to any product can actually increase HIV and STI transmission risk because it makes it easier for pathogens (germs) to enter the bloodstream. So it’s critical to have products that are safe, even when they are used several times a day. The issue of access is one of the fundamental goals of the Global Campaign. Advocates around the world are already working to make sure that microbicides are affordable and easily accessible and made available without a prescription. Finally, when using a microbicide, a woman wouldn’t need to gain her partner’s active cooperation at each act of intercourse – the way she has to with male or female condoms. Many women probably will choose to discuss microbicide use with their partners. But this could be a one time conversation -- and it wouldn’t have to happen right before sex. After that, the woman could manage her own protection without need to “negotiate” or interrupt sexual spontaneity every time.
Vaginal and rectal microbicides could work in similar ways. The first approach they’re using is pretty obvious -- coming up with products that just kill or disable HIV and other pathogens that come into the body. The trick here, of course, is to make something that kills pathogens but doesn’t irritate the epithelial lining of the vagina or rectum. Some products in this category are in vaginal trials but none are in rectal trials yet. Since the rectum is more fragile than the vagina, it may be difficult to create a product with this mechanism of action for the rectum. The second approach involves trying to enhance the body’s own ability to protect itself. One product in this category, called BufferGel, is designed primarily to keep the vaginal pH low even after ejaculation -- since low pH is one of the vagina’s defense mechanisms. A low pH can inactivate a substantial amount of HIV entering the body, as well as some other pathogens. Although rectal pH is naturally higher than vaginal pH, the creators of BufferGel feel that their product might still have some efficacy in reducing HIV risk in the rectum. Research is needed to see if the rectum can tolerate BufferGel without problems. In the test tube, BufferGel appears to inactivate not only HIV but also chlamydia and Human Papilloma Virus (HPV). The third approach involves creating products that make a barrier to keep pathogens, like HIV, from attaching to epithelial cells. We know that HIV has to attach to a cell in order to infect it. If it can’t attach, it can’t infect A fourth approach is to take some of the anti-retroviral drugs that many people with HIV take to reduce viral load and re-formulate them for topical use in the vagina or rectum. Products in this category are just going into vaginal trials but none are in rectal trials yet. In the end, we will ideally be able to combine these mechanisms for greatest effectiveness. (More details available from the Alliance for Microbicide Development – www.microbicide.org)
So how do microbicides work? The products now in the research pipeline fall into four basic categories -- defined by how they work. These are also known as ”mechanisms of action”. This slide is a picture of the vaginal wall and illustrates the different ways that candidate products might work to reduce infection. 12 1. The first approach is to build or improve upon what the body already does to protect itself. For example a healthy vagina is normally acidic, which makes it inhospitable to invading pathogens like HIV. But semen counteracts this acidity, creating an environment where HIV can survive. Some candidate microbicides build on the simple principle of maintaining the vagina’s natural acidic even in the presence of semen. 2. Surfactants disable the virus by breaking up its surface membrane or envelope. They can also disable sperm in the same way so they are also effective contraceptives. The trick is to make sure that surfactants are strong enough to disrupt the invading pathogen, but without damaging the healthy cells that line the vagina’s walls. 3. Entry inhibitors work by interfering with the virus getting into the body’s white blood cells—the target cells of HIV. There are two categories of entry inhibitors: attachment inhibitors that prevent attachment of the virus to the white blood cell and fusion inhibitors that prevent HIV from actually entering the cell. 4. Finally, some microbicides are being created by reformulating the same anti-retroviral drugs developed to treat people with HIV. These drugs are designed to stop HIV from replicating. So what happens if you make them into products that can be applied in the vagina? Could you stop the replication of any HIV that enters a vaginal cell so that the virus does not have a chance to disseminate and enter the blood stream? That’s what some researchers are trying to find out. The first microbicides to become available may operate with just one mechanism of action. It is very likely, however, that later generation microbicides will be combination products -- using two or more mechanisms of action to enhance their effectiveness.
As you saw earlier, there are currently three products in large scale effectiveness trials around the world. This slide shows the names of these products and the group running the trial in the first column, how many people the trials aim to recruit, where they are taking place, and when we can expect results assuming everything goes according to plan. 14 I like to show this slide not only so that you can become familiar with the names of the products but also to recognise the thousands of women who are involved in this endeavor. On average a woman in a current effectiveness trial will attend 29 study visits, including monthly visits for HIV and pregnancy tests, and have 11 pelvic exams and over 2 years. It is so important to recognise and honour their commitment. 16 Without their participation, it would be impossible to find out which, if any of these candidate microbicides, actually works. [Expected preliminary results. 15] [For a more technical audience, you can hand out a copy of the Global Campaign’s Factsheet #13 Clinical Trial Watch that describes these products in more detail – www.global-campaign.org/download.htm] [For a more information on the January 2007 Cellulose Sulfate trials closure, please see www.global-campaign.org/cellulose-sulfate.htm]
Microbicides will help people reduce risk of infection -- but we need to be clear about the fact that they aren’t going to eliminate risk. Microbicides will probably never be as effective as condoms. 7 It’s safer to keep a virus out of your body than it is to try to kill or disable it once it’s there. That’s common sense. But remember, we’re talking about microbicides as an option for people who can’t or don’t use condoms. The first microbicides are only likely to be 40-60% protective against HIV. The second generation microbicides may be 60-80% effective against HIV. 7 A condom with 80 to 95% effectiveness 8 is definitely the most effective disease prevention option, but it has ZERO effectiveness if a couple is not using it. It is our hope that although microbicides may be less effective, couples may be able to use them more consistently than they currently use condoms. So we should talk about microbicides as part of a risk reduction approach . We need to encourage people to continue to use condoms if they possibly can. Many folks may want to use microbicides with their condoms for back-up protection and added pleasure. Microbicides would give us something to suggest when a woman says “I just can’t make him use a condom. Isn’t there something else I can do to protect myself?” Once microbicides become available, we’ll be able to answer by explaining clearly that these new products aren’t as effective as condoms -- but they are much better than nothing. And, as we all know, a lot of women are getting infected because “nothing” is all they have.
Even if we are talking about partially effective microbicides that complement other interventions, they could still have a big impact. Computer modelling conducted at the London School of Hygiene and Tropical Medicine estimates that: 7 if a 60% effective microbicide is introduced in 73 low income countries with high HIV rates and gets used by only 20% of the people with access to existing health services and those people use it only half of the time when they’re not using condoms it could prevent 2.5 million new HIV infections among women, men & children over 3 years. 4 I’m not saying that this impact would be immediate. But we’re still talking about millions of lives potentially saved. And, as you see, these calculations are on relatively modest estimates of effectiveness, uptake and use. A more effective microbicide, used by a larger number of people, would have an even greater effect. Microbicides are not a panacea. But they could save a lot of lives and make an enormous difference in the spread of the pandemic. Now before I tell you more bout how microbicides work and where we are at in the research, are there any questions before we move on?
As you can see, drug development is a long and complicated process…taking more than a decade to develop and test a new drug for use. Before any new drug candidate can be tested in human beings, the developers have to show that (a) it’s not likely to be harmful to humans and (b) it may be beneficial. The research is done in laboratory testing and in animals and can take anywhere from 2 to 6 years. Currently there are over 30 candidates in pre-clinical testing (i.e. that is, that have not yet entered human testing). If a product is approved for human trials, it goes first through a series of Phase I safety trials, where small numbers of people who are at low risk of infection use the product and are carefully monitored for signs of problems. Next come one or more Phase II trials to gather extended safety data and establish safety among different groups of people–-for example, those who may already be HIV positive or have another sexually transmitted disease. If a product is shown to be safe in these first two phases, a product can then be tested for effectiveness. The Phase III trials can take several years because they need to enroll thousands of women who use the product for many months up to several years to see if it reduces their risk of HIV infection. It may be necessary to do two Phase III trials before a product can be licensed for use. While clinical trials are going on in women, researchers also need to undertake separate trials to look at whether the product is irritating to the penis or rectum. [ Products in Phase I/II are counted as Phase II and products from Phase II/IIB are counted as Phase III products. 13 ]
This slide is to give you a sense of where these trials are taking place. 14 As you see, Phase I and II safety trials are going on all over the world, but especially concentrated in the U.S. and Africa. To study effectiveness, a microbicide has to be tested by large numbers of women at high risk of sexually transmitted HIV. This means that the countries in which Phase III trials are carried out must have: · A high incidence of HIV · A stable population so that participants can be followed up easily · Almost no injecting drug use or other sources of HIV risk among women These conditions are found across sub-Saharan Africa and in India and parts of Southeast Asia. Places where HIV is prevalent among women in the North America and Europe also tend to have high rates of injecting drug use. This factor could confuse the trial results by introducing other sources of HIV risk. In part due to this reason, the majority of effectiveness trials are taking place in Africa as indicated here. [Map 21 ]
Results from the trials furthest along could become available in 2008, but it will take additional time for the products to be reviewed and approved for licensure – at least 1-2 years. Thus, we could be ready to introduce a product by 2010, but that would only happen in a few countries, and most likely through smaller scale introductory programmes. If the current set of products in effectiveness trials does not prove effective, the time horizon will be longer. There are several second-generation leads already in human testing, so we need to ensure that the entire pipeline continues to advance. Due to advocates work around the world and the recent attention on microbicides at the 2006 International AIDS Conference in Toronto, millions of people have heard about microbicides. The challenge that the microbicide field faces now is to find the correct balance between building enthusiasm and political support for microbicides, while avoiding raising unrealistic expectations in the media or our outreach work.
Every woman who is recruited for an effectiveness trial goes through a careful informed consent process in their own language and is tested for HIV and other STIs. Women who test positive for HIV can’t enroll in these first effectiveness trials because women have to be negative at the start of the trial to see how well the product helps them to remain negative. Women who test positive are connected to local providers of HIV-related care, treatment and support. Everyone in a Phase III trial receives state-of-the-art HIV prevention services. Right now, this means participants receive intensive risk reduction counseling, including condom counseling, large supplies of condoms and treatment for sexually transmitted infections if needed. All the women are encouraged to use condoms, whether they are given the active microbicide or not. In order to actually find out if the experimental microbicide works, the trial participants are randomly divided into two groups: Those who receive the condoms and prevention services plus the experimental microbicide gel. Those who receive the condoms and preventions services plus a placebo gel that looks just like the drug being studied but does not contain the active ingredient. An independent data safety monitoring board (DSMB) monitors the trials for any concerns that suggest the trial should be stopped. At the end of the trial researchers compare the two groups to see if the HIV rate is lower among those who received the microbicide versus those who received the placebo. If it is, that difference is the measure of the microbicide’s effectiveness. Trials can also bring increased health care, prevention services and treatment access into highly-impacted communities. How those services are provided and how well they are continued after the trial is a subject of intense ethical debate among researchers and communities. One of the Global Campaign’s functions is to help trial communities prepare to advocate effectively for their communities during this process.
Formulating a microbicide for rectal use is more challenging than making one for vaginal use just because the rectum is a very different environment. First of all, it’s an open ended cavity. The vagina is a closed pouch. You can coat the inside of the vagina with about 3-5 milliliters of product. Since the rectal cavity isn’t closed, it could require significantly more product to protect the rectal walls where they need protection. One of the key questions scientists are trying to answer now is exactly how much product it will take and what areas have to be covered to get a good protective effect. Rectal tissue is also more fragile than the tissue lining most of the vagina. It is is thinner and populated with cells that are especially vulnerable to HIV infection. 6 Research has begun to develop rectal microbicides. They are urgently needed -- not only by gay men but also by the many women who engage in anal intercourse. The International Rectal Microbicide Working Group brings together advocates and researchers, and now has over 200 members. You can find out more through the Global Campaign website. But until we have an effective rectal microbicide, we have to insist that all vaginal microbicides nonetheless be tested for safety in the rectum, even if not designed for that use. And products designed for vaginal use must be carefully labeled to alert users that they should not be used rectally, until proven safe and effective for rectal use. [Note: if the audience is particularly interested in rectal microbicides, visit www.global-campaign.org/download.htm for a factsheet and complete presentation on rectal microbicides. Also visit www.lifelube.org]
We need to work towards an expanded toolkit of HIV prevention and treatment to combat this epidemic. Right now, we have many tools that people can use before exposure, right at he point of HIV transmission, and also after being infected. Admittedly we need to improve people’s access to these existing tools—we need to make sure that male and female condoms are available to those who need them at an affordable price, and that women can access prevention of mother to child transmission services when they need them. [Speaker can indicate existing interventions in blue] Advocates and researchers around the world are also working to see if there are new options that we can add to this spectrum in the near future. [Speaker can indicate new interventions in pink] [Speaker may choose to use this slide only with audiences who are familiar with the field of HIV/AIDS.] VCT is voluntary counseling and testing for HIV PREP is pre-exposure prophylaxis PMTCT is prevention of mother to child transmission PEP is post-exposure prophylaxis
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Quote from last slide: Quote found in UNICEF, Facing the Future Together: Report of the Secretary-General's Task Force on Women, Girls and HIV/AIDS in Southern Africa, July 2004. http://www.unicef.org/publications/SGs_report_final.pdf – Quote from UNICEF’s Voices of Youth, www.unicef.org/voy References: Remember! Updates of this presentation are available at www.global-campaign.org/download.htm