Dapivirine Safety MTN 025 Training

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

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

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

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

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

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

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%)

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

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