1. Dapivirine Safety
MTN 025 Training

2. Outline Dapivirine Safety outcomes from ASPIRE
Safety outcomes from the ring study
Resistance concerns
Early pregnancy exposure
The ring!

3. Dapivirine
Dapivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI)
There were no preclinical concerns surrounding the drug
Early clinical trials also supported a good safety profile

4. Safety Outcomes from ASPIRE
No significant differences in the frequency of primary safety end points
No differences in incident sexually transmitted infections
No differences in the following complaints that were assessed by the managing clinician as RELATED
Cervicitis, PID, UTI, Neutrophil decrease, abnormal loss of weight, headache, dysmenorrhea, dyspareunia, pelvic pain, pruritis

5. Safety Outcomes from the Ring Study
No clinically significant differences in safety parameters
The incidence of the top 3 GU events were the same between groups
Metrorrhagia
Genital infection
Menorrhagia

6. Resistance Concerns
In the lab, suboptimal concentrations of dapivirine alone facilitated the emergence of common NNRTI resistance
In ASPIRE, there was no difference in the numbers of participants with NNRI mutations suggestive of antiviral resistance
8/68 in dapivirine
10/96 in placebo
In the Ring Study, detection of NNRTI mutations amongst HIV-1 infected participants were the same

7. Early Pregnancy Exposure
The bulk of safety data in pregnancy comes from registries
There is almost NO data surrounding the safety of dapivirine in pregnancy
MTN-016
In contrast to Truvada and Tenofovir during VOICE

8. The Ring Itself
Both ASPIRE and the Ring Study had placebo ring arms so the comparison between study arms looks ONLY at the DRUG
IPM-011 provides data surrounding the 004 ring itself
Cross over study between ring and no ring (IPM011)
Ring
Observation
UTI
7 (4.4%)
3 (1.9%)
Candidiasis
18 (11.4%)
17 (10.6%) BV
15 (9.5%)
13 (8.1%)
Trichomoniasis
1 (0.6%)

9. Conclusions
Before ASPIRE and The Ring Study, no safety concerns but limited data
After these studies, EXTENSIVE experience and no safety concerns
Resistance concerns remain, but have not born out
Anticipate that dapivirine will be safe in pregnancy, but this needs to be studied formally to say

10. Questions?