CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

(PY), assuming a 5/100 PY IR in arm B based on reports in non-pregnant HIV- positive adults. Secondary outcomes were maternal hepatotoxicity, maternal/ infant death, TB, adverse pregnancy outcomes, and infant AE. Results: Among 956 enrolled, 93%were black, median age was 29 years, median CD4 was 493 cells/µL, 30%were IGRA+, 955 (>99%) were on ART (85% efavirenz-based), 63% had undetectable HIV-1 RNA, and 34%were 14-<24 weeks GA. Median follow-up was 58.6 weeks. 147 (15%) reached the primary outcome (74 in arm A, 73 in arm B), with IRs 15.4 and 14.9/100 PY, respectively (IR difference=0.5/100 PY, [95%CI: -4.4, 5.4]; Table).171 women discontinued the study prematurely; 6 died (2 in arm A, 4 in arm B), with 3 deaths due to treatment-related hepatotoxicity (1 in arm A, 2 in arm B) and one non-treatment-related hepatotoxicity in arm B; 77 withdrew consent (most after DSMB and sponsor-required safety memo about risk of death from IPT); 75 were lost to follow-up. There were no statistical differences in IRs of any maternal grade ≥3 AE, all-cause hepatotoxicity, or infant grade ≥3 AE between arms. There was no difference in maternal TB or infant TB by study arm. Adverse pregnancy outcomes however were significantly higher in arm A vs. B (23% vs 17%; p=0.009). Conclusion: IR for the primary safety outcome was higher than expected and similar for immediate vs. deferred IPT, but did not meet the pre-specified NIM. TB incidence was low. Of note, immediate IPT was associated with excess adverse pregnancy outcomes. The recommendation to initiate IPT during pregnancy in HIV-positive women on ART needs re-evaluation.

bootstrap sampling of the placebo arm of ASPIRE, selecting 10,000 times for a subset of women matched on trial site, age, and presence of a curable sexually transmitted infection at trial entry. Results: Between August 2016 and October 2017, 1407 women enrolled into HOPE, 57% of those HIV-1 uninfected at completion of ASPIRE. The median age was 31 years (IQR 27-37), with 13% aged 20-24 and 28% 25-29 years; 16% had a curable sexually transmitted infection. Of 1407 enrollees, 1299 (92%) accepted the dapivirine vaginal ring. 89% of returned rings had residual dapivirine levels consistent with some use during the prior month. A total of 12 HIV-1 infections in 616 person-years of follow-up have been observed (incidence 1.9 per 100 person-years, 95% CI 1.0-3.4). Given the site, age, and sexually transmitted infection distribution of the population enrolled, HIV-1 incidence was expected to be 4.1 per 100 person-years (95% CI 3.2-5.1) in the absence of access to the dapivirine vaginal ring, and an incidence of 1.9 would be expected to occur with a frequency of less than 1 in 10,000 samplings. Conclusion: Interim results from this open-label extension trial of the dapivirine ring demonstrate high uptake and adherence, and HIV-1 incidence has been half of the expected rate. These findings are limited by the lack of a contemporaneous placebo group and prior participation of the study population in ASPIRE, but they suggest important HIV-1 prevention effectiveness of the dapivirine vaginal ring when used by African women in an open-label setting. 144LB HIV INCIDENCE AND ADHERENCE IN DREAM: AN OPEN-LABEL TRIAL OF DAPIVIRINE VAGINAL RING Annalene Nel 1 , Neliette Van Niekerk 1 , Ben Van Baelen 2 , Zeda Rosenberg 3 1 International Partnership for Microbicides, Paarl, South Africa, 2 BVB Clin Consult, Herent, Belgium, 3 International Partnership for Microbicides, Silver Spring, MD, USA Background: The monthly Dapivirine Vaginal Ring (DVR; 25 mg) was evaluated for safety and efficacy in two Phase III clinical trials, The Ring Study and ASPIRE. The trials demonstrated that the ring was safe and reduced the risk of HIV-1 infection in women, 18 to 45 years, by ≈ 30% relative to placebo. DREAM is an ongoing Phase IIIb, multi-center, open-label follow-on trial to The Ring Study to evaluate continued safety and adherence to ring use. The preliminary results are presented. Methods: Women who participated in The Ring Study and who were HIV- negative at screening for DREAM were eligible for enrolment at 5 Research Centers (RCs) in South Africa and 1 in Uganda. Monthly RC visits take place up to 3 months after enrolment, whereafter participants continue on a quarterly visit schedule. HIV testing and safety evaluations are conducted at each visit, and used rings are returned for analysis of dapivirine residual levels. HIV-1 incidence was compared descriptively to the rate expected by bootstrap sampling, based on the placebo arm of The Ring Study, selecting 10,000 times for a subset of women matched for RC, age, and presence of a curable sexually transmitted infection (STI) at enrolment. Results: By September 2017, 900 women were enrolled in DREAM. The median age was 29 years (range: 20-50); 3%were ≤21, 24%were >21 and ≤25; 33% were >25 and ≤30; 21%were >30 and ≤35; and 19%were >35 years. A total of 11 HIV-1 seroconversions in 623 person-years (PY) of follow-up was observed on product: an incidence rate of 1.8 per 100 PY (95% CI: 0.9-3.2). Based on RC, age, and STI distribution of the population enrolled, HIV-1 incidence was expected to be 3.9 per 100 PY (95% CI: 2.9-4.9) in the absence of DVR use. An incidence of 1.8 per 100 PY would be expected to occur with a frequency of less than 1 in 10,000 samplings. Only 4% of returned rings had a residual level >23.5 mg, indicative of non-adherence to ring use, compared to 17% in The Ring Study. Eleven serious adverse events were reported, all unrelated to ring use. Conclusion: Preliminary results from DREAM indicate a similar safety profile of DVR to that observed in Phase III. Based on dapivirine ring residual levels, adherence to ring use is higher. Although interpretation is limited by the lack of a placebo arm, the observed HIV-1 incidence rate is ≈ 54% lower than the expected rate in the absence of access to DVR, supporting the hypothesis that increased efficacy would occur when participants knew the DVR’s safety and efficacy from Phase III.

Oral Abstracts

143LB HIGH UPTAKE AND REDUCED HIV-1 INCIDENCE IN AN OPEN-LABEL TRIAL OF THE DAPIVIRINE RING Jared Baeten 1 , Thesla Palanee-Phillips 2 , Nyaradzo Mgodi 3 , Ashley Mayo 4 , Annalene Nel 5 , Zeda Rosenberg 5 , Sharon L. Hillier 6 , Elizabeth Brown 7 1 University of Washington, Seattle, WA, USA, 2 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 3 University of Zimbabwe, Harare, Zimbabwe, 4 FHI 360, Durham, NC, USA, 5 International Partnership for Microbicides, Paarl, South Africa, 6 University of Pittsburgh, Pittsburgh, PA, USA, 7 Fred Hutchinson Cancer Research Center, Seattle, WA, USA Background: Two phase III clinical trials (MTN-020/ASPIRE & IPM 027/The Ring Study) demonstrated that a monthly vaginal ring containing dapivirine was safe and reduced HIV-1 incidence by approximately 30% compared to placebo. For tenofovir pre-exposure prophylaxis (PrEP), adherence and HIV-1 prevention effectiveness have often been greater in open-label studies than in earlier placebo-controlled trials. We are conducting MTN-025/HOPE, a phase IIIb open- label extension trial of the dapivirine vaginal ring; a planned interim analysis of data was conducted in October 2017. Methods: HIV-1 uninfected women who had participated in ASPIRE are offered 12 months of access to the dapivirine vaginal ring in HOPE at 14 sites in Malawi, South Africa, Uganda, and Zimbabwe. Used rings are returned at each study visit (monthly for 3 months, then quarterly) and are tested for residual levels of dapivirine. HIV-1 incidence in HOPE was compared to that expected by weighted

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CROI 2018