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Microbicides for HIV Prevention
Pamina M. Gorbach, Epidemiology & Infectious DiseasesUCLA
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-irritatingTo be inexpensive and available over the counterTo 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. Different dosing is being tested in trials.These include application 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: Effectiveness – Do they work?
Who is doing the research?
Research entity Examples Funding sources
Not-for-profit health groups and academic institutions
MTN, CONRAD, FHI, CAPRISA
Governments (South Africa DST, US NIH, UK DFID), philanthropic foundations
Public-private partnerships
IPM European/US/Canadian governments, philanthropic foundations, UNFPA, World Bank
Smaller pharmaceutical companies
EndoStarPharma
Venture capital, some government grants
Outcomes of first trials – not good
Signs of efficacy No efficacy
SafeCarraguard®BufferGel®
PRO 2000 0.5%
Trend toward harm
Nonoxynol-9Savvy
Cellulose sulphate
FACTS 001: Follow-on African Consortium for Tenofovir Studies
Compared HIV infection rates between 2 groups of sexually active HIV-women aged 18–30 in nine sites in South Africa (n=2,059): those assigned a vaginal gel containing
tenofovir for use before and after sex those who received a placebo gel
New HIV infections occurred at the same rate in both groups: The HIV incidence was 4% in both groups
Showed that the results of CAPRISA 004 could not be replicated in a large study population comprising diverse women across South Africa.
In this trial, overall use of the gel by participants was low.
VOICE 2.0 (MTN 003)
5,000 Women
Tablet(3,000)
Vaginal Gel(2,000)
Truvada(1,000)
Tenofovir(1,000)
Placebo Tablet(1,000)
Tenofovir Gel(1,000)
Placebo Gel(1,000)
VOICE: Primary Efficacy Results.
Marrazzo JM et al. N Engl J Med 2015;372:509-518
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.
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 gel in the VOICE study (MTN 003). 20th Conference on Retroviruses and Opportunistic Infections. Atlanta. March 3 –6, 2013. Abstract #26LB.
Rectal Microbicides
MSM Throughout the World Need HIV Prevention
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
Anal Intercourse: Lifetime (ever)NSFG US General Population
Lubricants are Popular for AI
Peri-sexual behaviors: Rectal Douching Common
Rectal and Vaginal Mucosa Are Very Different
Histology ImmunologyMicrobiology
Differential susceptibility to candidate microbicides
MTN 017 A Phase 2 Randomized Sequence Open
Label Expanded Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel.
So Where Now?
MTN -017 Progress – Enrolled!
ASPIRE – Enrolled! Multi-site randomized controlled Phase III
trial of Dapivirine vaginal ring for HIV prevention
3,476 women enrolled in South Africa Phase I Safety Study of Post-Menopausal women in US completed
Phase I Safety Study of Adolescent girls in US (done with ATN) in process
59/96 enrolled.
Coming Up
Issues with Microbicides Many provide only partial protection : How will people
interpret this?
What will be best medication schedules (daily, weekly, activity-based, long-acting (30-90 days)?
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 pay for them?
Will there be an increase in risk behavior?
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 Good News Rectal Microbicides looking promising Rings seem to have high adherence
The 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 “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
Summary: State of the Science Vaginal gel---unclear effectiveness in preventing HIV in
women due to low adherence – not moving forward
Vaginal rings and injectables seem to show promise for women – under “Microbicides” umbrella
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!