CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

Results: By 12m postpartum 30% of women in the cohort experienced VE after VS. In 107 cases and 124 controls, median duration on ART was 42w. Cases were younger with greater previous ARV exposure and higher pre-ART VL. At the time of VE, ARVs were detected in 17% of cases, compared to 89% of preceding samples from the same women when VS, and 94% of VS controls sampled at the corresponding time on ART (both adjusted p<0.001). Pre-ART DRM were detected in 11% of cases and 5% of controls, all NNRTI-related. At the time of VE, 45% of cases had DRM (almost all major NNRTI mutations). Of 12 women with pre-ART DRM, most (92%, n=11) experienced VE, and of these, most (82% n=9) had the same DRM detected again during VE. However these 9 women were a minority (19%) of all women with DRM during VE (n=48) most of whom had no DRM detected pre-ART and no previous ARV exposure. Conclusion: The vast majority of VE in this setting are explained by ART non- adherence; the frequency of early VE and rapid emergence of NNRTI DRM during VE have implications for long-termmaternal outcomes and choice of optimal ART regimens.

Methods: A5316 was an international, multicenter, longitudinal, parallel group, pharmacokinetic (PK) evaluation of HIV-positive women ≥ 16 years old. A vaginal ring releasing ENG/EE 120/15 mcg/day was inserted at entry in three groups of participants: (1) not yet receiving ART (control group; n=25); (2) ART containing EFV 600mg daily (EFV group; n=25); (3) ART containing ATV/r 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21). Demographics are summarized as mean (standard deviation) or frequency (%). Results: Overall, 74 evaluable women were 35 (7.6) years of age, 72.5 (24.2) kg, 37 (50%) Black, and 26 (35%) Hispanic. ENG and EE PK results are described and compared between groups in the Table. Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. Conclusion: Both EFV- and ATV/r-based ART altered systemic hormone exposure delivered via a vaginal ring; these changes were similar or greater to prior DDI studies with oral hormonal contraceptives. Women on EFV- or ATV/r-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood. These data highlight the importance of evaluating DDIs between ART and non-oral hormone contraceptive methods during novel drug product development.

Oral Abstracts

142LB RANDOMIZED TRIAL OF SAFETY OF ISONIAZID PREVENTIVE THERAPY DURING OR AFTER PREGNANCY Amita Gupta 1 , Grace Montepiedra 2 , Lisa Aaron 2 , Gerhard Theron 3 , Katie McCarthy 4 , Carolyne Onyango-Makumbi 5 , Tsungai Chipato 6 , Gaerolwe Masheto 7 , Katherine Shin 8 , Bonnie Zimmer 9 , Timothy R. Sterling 10 , Nahida Chakhtoura 11 , Patrick Jean-Philippe 8 , Adriana Weinberg 12 1 Johns Hopkins University, Baltimore, MD, USA, 2 Harvard University, Boston, MA, USA, 3 Stellenbosch University, Cape Town, South Africa, 4 FHI 360, Durham, NC, USA, 5 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 6 University of Zimbabwe, Harare, Zimbabwe, 7 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 8 NIAID, Bethesda, MD, USA, 9 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 10 Vanderbilt University, Nashville, TN, USA, 11 National Institute of Child Health and Human Development, Bethesda, MD, USA, 12 University of Colorado Denver, Denver, CO, USA Background: The safety, efficacy, and optimal timing of isoniazid preventive therapy (IPT) for HIV-positive pregnant women on antiretroviral therapy (ART) is unknown. We hypothesized that IPT can be safely initiated during pregnancy. Methods: A Phase IV randomized, double-blind, placebo-controlled trial compared initiation of 28 weeks of IPT in antepartum (AP; immediate) (arm A) versus at 12 weeks postpartum (PP; deferred) (arm B) in HIV-positive women from TB-endemic areas in Africa, Asia, and Haiti. Randomization 1:1 was stratified by gestational age [GA] (14-<24 weeks, 24-34 weeks); mother-infant pairs were followed to week 48 PP, with safety evaluations performed every 4 weeks. The primary safety endpoint was treatment-related maternal adverse events (AE) ≥ grade 3 or permanent drug discontinuation due to toxicity. The non-inferiority margin (NIM) was an incidence rate (IR) of 5/100 person-years

141 VAGINAL CONTRACEPTIVE HORMONE EXPOSURE PROFOUNDLY ALTERED BY EFV- AND ATV/R-BASED ART Kimberly K. Scarsi 1 , Yoninah S. Cramer 2 , David Gingrich 3 , Susan L. Rosenkranz 2 , Francesca Aweeka 3 , Robert Coombs 4 , Carmen D. Zorrilla 5 , Kristine Coughlin 6 , Laura E. Moran 7 , Baiba Berzins 8 , Catherine Godfrey 9 , Susan E. Cohn 8 1 University of Nebraska Medical Center, Omaha, NE, USA, 2 Harvard University, Cambridge, MA, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 University of Washington, Seattle, WA, USA, 5 University of Puerto Rico, San Juan, Puerto Rico, 6 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 7 Social &Scientific Systems, Silver Spring, MD, USA, 8 Northwestern University, Chicago, IL, USA, 9 DAIDS, NIAID, Bethesda, MD, USA Background: Contraceptive hormones delivered by a vaginal ring result in stable systemic hormone exposure over 21 days of use, with concentrations that are lower than those observed with oral or injectable contraceptives. Drug-drug interactions (DDI) exist between oral hormonal contraceptives and some antiretroviral therapy (ART), but the impact of ART on hormone exposure when released from a vaginal ring is not known. We hypothesized that efavirenz (EFV)-based ART and atazanavir/ritonavir (ATV/r)-based ART would alter plasma concentrations of vaginally administered etonogestrel/ethinyl estradiol (ENG/ EE).

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CROI 2018