Transcript mtn 020 aspire - UZ-UCSF

A Phase III Trial of the
Dapivirine Vaginal Ring
for HIV-1 Prevention in Women
On behalf of The MTN-020/ASPIRE Study Team
UZ-UCSF Annual Research Day 8 April 2016
Why was the ASPIRE study done?
• Women in Africa, especially
young women, have been
among the hardest hit by HIV.
• They desperately need HIV
prevention tools that are safe,
effective and easy to use.
PrEP: Pre-Exposure Prophylaxis
• Studies have proven that daily use of an ARV
tablet (PrEP) is very effective in preventing
HIV.
• However, PrEP studies among African women
did not have similar results due to low
adherence to the products (tablets or gels).
MTN-020/ASPIRE
•
•
MTN-020/ASPIRE was a multi-center,
randomized, double-blind, placebocontrolled phase III trial of a silicone
elastomer vaginal matrix ring containing
the non-nucleoside reverse transcriptase
inhibitor dapivirine (25 mg).
This vaginal ring was inserted once every
4 weeks in healthy sexually active HIV-1
uninfected women (18-45 years).
ASPIRE Study Questions
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Will the ring prevent HIV?
Is the ring safe?
Is the ring acceptable?
Will women use the ring (adherence)?
If a woman becomes infected with HIV,
will drug resistance be a problem?
Trial Design
•
At enrollment, women were
randomized 1:1 to dapivirine:placebo.
•
Women were counseled to wear the
ring continuously, and a new ring was
provided at scheduled monthly visits.
•
Follow-up was for a minimum of 1 year.
•
All received a comprehensive package
of HIV-1 prevention services.
Who enrolled in ASPIRE?
• 2,629 women enrolled at 15
sites in 4 countries:
–272 in Malawi (2 sites)
–1,426 in South Africa (9 sites)
–253 in Uganda ( 1 site)
–678 in Zimbabwe (3 sites)
Who enrolled in ASPIRE?
Average age 26 (range 18-45)
Less than half (41%) were married
Nearly all (>99%) reported a primary sex partner & 17%
reported more than one partner in the prior 3 months
Nearly half did not use a condom
with their last sex act
How do we know if the ring is effective?
• We compared the number of HIV
infections that occurred in the
dapivirine ring group with those in the
placebo ring group
• If effective, we would expect that
fewer women in the dapivirine ring
group would acquire HIV
Vs.
Dapivirine
Placebo
HIV-1 Protection
Overall, women in the dapivirine vaginal ring arm had a 27%
reduction in the rate of HIV-1 acquisition, compared to placebo.
Primary HIV-1 effectiveness
intention-to-treat analysis (15 sites)
Dapivirine
Placebo
# HIV-1 infections
71
97
HIV-1 incidence,
3.3
4.5
per 100 person-years
HIV-1 protection
effectiveness
95% CI, p-value
27%
(1, 46)
p=0.046
HIV-1 Protection
After excluding data from two sites with lower adherence, the
dapivirine ring reduced HIV-1 acquisition by 37%.
Primary HIV-1 effectiveness
intention-to-treat analysis (13 sites)
Dapivirine
Placebo
# HIV-1 infections
54
85
HIV-1 incidence,
2.8
4.4
per 100 person-years
HIV-1 protection
effectiveness
95% CI, p-value
37%
(12, 56)
p=0.007
In other words, the ring prevented about one-third of HIV infections –
about one in three women who would have been infected was not.
HIV Uninfected
HIV protection differed significantly by age
Combined, there were 56% fewer HIV infections among women
older than age 21.
No reduction
56% reduction
Age 18-21
Older than 21
In other words, among women older than 21, the ring prevented over one
half of HIV infections – about one in two women who would have been
infected was not.
HIV Uninfected
Adherence was strongly related to age
• Blood samples and used
ring testing showed that
younger women were
less adherent to the ring
Age 27-45
Age 22-26
Age 18-21
Younger Women
• Both behavioral and biologic effects may
have contributed to a lack of HIV
protection in women aged 18-21 in ASPIRE.
• Further research is needed to understand
the unique prevention needs of young
women.
Safety
• The dapivirine vaginal ring was shown to be very safe
• No difference in the number of adverse events (health
problems), pregnancies, or HIV drug resistance was
observed between study groups
MTN Next Steps…
• Open-Label Extension (OLE) of ASPIRE study
– Primary purpose would be to offer access to
dapivirine vaginal ring (active study product) to
former ASPIRE participants who are eligible
– Would also collect data on safety and adherence in
the context of open-label use
MTN-020/ASPIRE Summary
• In MTN-020/ASPIRE, a monthly vaginal ring
containing dapivirine safely helped to
protect against HIV in African women.
– Risk was reduced by ~1/3 overall and by >1/2 among
those aged ≥22
• HIV protection was greater in groups
with evidence of better adherence to
ring use.
Conclusions
Our results, with those of The Ring Study,
demonstrate that the dapivirine vaginal ring can
protect against HIV.
Conclusions
The ring was not protective in young women, who
had lower adherence—more research is needed to
understand both biologic and behavioral factors in
this vulnerable age group.
ASPIRE Team
Participants and communities