Transcript Microbicides for HIV Prevention

Microbicides for HIV
Prevention
Pamina M. Gorbach,
Epidemiology & Infectious
Diseases
UCLA
MTN, ATN
What is a microbicide?
….a product applied inside the
vagina or rectum that are
intended to protect against HIV
though sex. Microbicides that
incorporate antiretroviral (ARV)
drugs are showing particular
promise.
Microbicides



First generation:

Gels & creams for rectum or vagina

Inserted daily or before and after sex
Current generation:

Vaginal rings: Inserted and remain in place for > 1 month

Pills: PrEP (Pre-exposure prophylaxis)
Future: Injectables, film?
What Do Participants Need from
HIV Prevention Methods?
To
reduce risk of HIV and other STIs
To
prevent pregnancy and not prevent pregnancy!
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
Photo courtesy of http://www.mtnstopshiv.org/
If microbicides work…
1. Only taken if you KNOW you are HIV negative.
 So regular HIV testing is necessary.
2. May be available by prescription only.
 So access to a qualified health care provider is
necessary.
3. Only the dosing used in trials is known to work.
 For now, must be applied daily or before and
after sex.
Why would HIV+ people want
microbicides?
Reduce risk of:
 Infection
with multiple strains of HIV
 Infection
with other STIs, yeast or bladder infections
Women can get pregnant while still protecting their
partner from HIV.
Findings from Recent
Microbicide Trials:
Acceptabilty
Product Acceptability (MTN-006)



Only 3 of 12 participants
in the tenofovir arm liked
the gel very much.
5 of 12 felt discomfort
Nevertheless, 9 of 12
indicated they were very
likely to use the gel in the
future.
This could mean participants are concerned enough about
HIV to tolerate discomfort & unpleasant product
characteristics.
Gel vs Pill
 MTN
001: Phase 2 Adherence and
Pharmacokinetics Study of Oral and
Vaginal Preparations of Tenofovir Enrolled144 sexually active HIV-negative
women at sites in Uganda, South Africa
and the United States for 21-weeks.
 Each
follow each regimen (pill & gel) for
six weeks, with one week between when
no study product is used.
 72
women enrolled at the two U.S. sites
Oral/Vaginal acceptability
(MTN 001)
Factors that facilitated use: Product properties
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increased lubrication improved sexual intercourse due to (gel) African sites
Reduced vaginal dryness (gel)
Discreetness of pill taking (especially relative to gel insertion)
Cultural and personal familiarity with pills - US sites
Ease of use (tablet)
Products bestowed unanticipated benefits: cleansing,
menstrual cramps stopped
 Product


properties disliked
Gel: Consistency and leakiness; External irritation; Vaginal
tightness; Insertion and disposal of product applicators
Tablets: Side-effects (nausea, hunger, fatigue); Pill size
Qualitative Findings: MTN 001
End of Study In-depth Interviews
 Product
preferences and barriers to use differed
among women; clear interest in both products.
 Gel
perceived to improve sex by many women at
Ugandan and South African sites, suggesting
broader perceived sexual health benefits:
“Since I started using it, the love with my husband
increased…because he thinks I love him so much yet it’s the
gel.” –Ugandan participant.
 Minor
side effects numerous, but subsided swiftly.
Product Acceptability in MTN-001
Vaginal
Gel
Oral
Tablets
Dual
All sites†
83
93
82
African sites
100
100
99
United States sites
64
87
65
Future product use likely if
proven effective
† p=0.002 (conditional logistic regression, controlling for period and sequence)
Geographic differences in reporting future willingness to use
products.
Participants less comfortable with interviews? Did this affect their
responses/behavior?
Lessons Learned: Acceptability
 Cultural


differences need further study
Puerto Rico vs. U.S. (MTN-004/ATN-062):
better acceptability in Puerto Rico
Africa vs. U.S. (MTN-001) – More gel
preference in Africa; US women prefer pills
 The
risk environment may be as important
as gel characteristics

Women may “forgive” characteristics if a
product is effective or they perceive
themselves at high risk (segue to next slide)
Findings from Recent
Microbicide Trials:
Effectiveness – Do they
work?
Outcomes of first trials – not good
Signs of efficacy
Safe
Trend
toward harm
No efficacy
Carraguard®
BufferGel®
PRO 2000 0.5%
Nonoxynol-9
Savvy
Cellulose sulphate
VOICE 2.0 (MTN 003)
5,000 Women
Tablet
(3,000)
Truvada
(1,000)
Tenofovir
(1,000)
Vaginal Gel
(2,000)
Placebo Tablet
(1,000)
Tenofovir Gel
(1,000)
Placebo Gel
(1,000)
Marrazzo, J. et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral
tenofovir/emtricitabine, or vaginal tenofovir gel in the VOICE study (MTN 003). 20th
Conference on Retroviruses and Opportunistic Infections. Atlanta. March 3–6, 2013.
Abstract #26LB.
Marrazzo, J. et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir
Conclusions: VOICE
 Incidence
of HIV substantially higher than
anticipated
 No study drug significantly reduced risk of HIV
 Adherence to study products was low, especially
among younger, unmarried women
 Results consistent with FEM-PrEP

Consider PrEP agents/delivery systems that are long
acting and require minimal daily adherence
 Understanding
HIV risk perception and biomedical,
social and cultural determinants of adherence in
this high-risk population urgently needed
Marrazzo, J. et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir
Adherence in FemPrEP
ADAPTED FROM
Van Damme L,
CorneliA, Ahmed K,
Agot K, Lombaard J,
Kapiga S, et al. The
FEM-PrEP Trial of
Emtricitabine/
Tenofovir Disoproxil
Fumarate (Truvada)
among African
Women. In:
Conference on
Retroviruses and
Opportunistic
Infections (CROI), .
Seattle; 2012.
Rectal
Microbicides
Anal Intercourse: Lifetime (ever)
NSFG US General Population
Chandra A, Mosher WD et al. Sexual Behavior, Sexual Attraction, and Sexual Identity in the United States: Data From
the 2006–2008 National Survey of Family Growth. National Health Statistics Reports n Number 36 n March 3, 2011
International: Women Reporting
Ever AI
Brazil: Silveira MF, 2002; Caetano ME, 2010
South Africa – Lane, Pettior et al 2006
Peru: Caceres C et al. 1997
Kenya: Schwandt M et al. 2006
China (Anhui) : Lui H et al 1998
Nigeria: Bamidele et al 2009 (combined gender)
MSM Throughout the World
Need HIV Prevention
Lubricants are Popular for AI
Peri-sexual behaviors: Rectal
Douching Common
Rectal and Vaginal Mucosa Are
Very Different
 Histology
 Immunology
 Microbiology
 Differential
susceptibility to
candidate
microbicides
So Where Now?
Issues with Microbicides
 Many
provide only partial protection : How will people
interpret this?
 How
will consistent use be maintained & supported?
 How
could different medication schedules (daily,
weekly, activity-based) be introduced?
 How



often & who will track:
Adherence/consistent use
Drug resistance
New HIV infections by users (seroconversion)
Other Issues
 Who
will get the products? Should adolescents?
Pregnant women? Transgender?
 For
how long should/could they be used?
 Who
 Will
will pay for them?
there be an increase in risk behavior?
What is drug resistance?

HIV makes thousands of copies of itself
daily.

Every time HIV copies itself, errors can
occur, like typing errors on a page.

These are mutations—changes that
can make the virus weaker or stronger.

A mutation that makes HIV able to
resist an ARV drug = drug-resistant HIV.
Drug resistance from microbicides?
 Most
likely when using only one drug or one type
of ARV.
 Can
become HIV+ while using microbicide.
 Continued
use (you don’t know you’re HIV+)
may lead to resistance.
 Options
for treatment may be more limited—you
might pass on resistant virus.
 There
are unanswered questions at this point.
In a nutshell: Acceptability
 The

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Positive result from one topical gel trial (CAPRISA 004)
Rectal Microbicides looking promising
 The
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Bad News
Some participants may not satisfied with current
product characteristics and dosing
Adherence vastly under-reported & products not used
in trails enough to detect effectiveness
 The

Good News
“Ugly” news
Not everyone (dis)likes the same things, and there will
need to be product choices
Creating Desire for Microbicides
To enjoy (the gel)
first you need to
use it
Who is doing the research?
Research entity
Examples
Funding sources
Not-for-profit health
groups and academic
institutions
MTN,
Governments (South
CONRAD,
Africa DST, US NIH, UK
FHI, CAPRISA DFID), philanthropic
foundations
Public-private
partnerships
IPM
European/US/Canadian
governments,
philanthropic
foundations, UNFPA,
World Bank
Smaller
pharmaceutical
companies
Endo
StarPharma
Venture capital, some
government grants
Summary: State of the Science

Vaginal gel---effective in preventing HIV in women if used
before and after sex  (CAP 004)

Rectal gel---shown to prevent HIV in Phase I trial in men
and women 

Cultural differences:
 African women may prefer a vaginal gel
 U.S. women may prefer a pill
Bottom Line: People may have choices!