CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

endpoint, the safety endpoint, and WHO 2 and 3 events were similar to those previously reported in both arms of the FF women in 1077HS (Table). Conclusion: In the largest multi-site, perinatal, randomized trial to date evaluating postpartum ART, serious clinical events were rare among women with high CD4 cell counts over 18 months after delivery, regardless of whether they received postpartum ART. Outcomes appear similar between a cohort of predominately BF women compared to FF women, suggesting no adverse impact of prolonged BF on health outcomes in women with high CD4 counts.

AEs in women who continued ART compared to those who discontinued ART (p<0.05). Grade 2 or higher AEs were also higher in women who continued ART (p=0.08). This difference was mostly driven by signs and symptoms (p- value=0.01) with more frequent Grade 3 weight loss in the continue ART arm (13 Grade 3 weight loss and 1 Grade 4 weight loss) compared to discontinue arm (5 Grade 3 weight loss and no Grade 4 weight loss). Conclusion: AIDS-defining illness, death, or clinical events were rare in both arms (0.23% per 100 person-years overall). However, rates of several AEs were higher in the continue ART arm compared to the discontinue ART arm.

Oral Abstracts

139 PROMISE TRIAL: RESULTS OF CONTINUED VS DISCONTINUED ART AFTER END OF BREASTFEEDING Taha E. Taha 1 , Sean Brummel 2 , Konstantia Angelidou 2 , Mary Glenn Fowler 1 , Patricia M. Flynn 3 , Cornelius Mukuzunga 4 , Dingase E. Dula 5 , Maxensia Owor 6 , Dhayendre Moodley 7 , Tsungai Chipato 8 , Amy J. Loftis 9 , Nahida Chakhtoura 10 , Katie McCarthy 11 , Judith S. Currier 12 1 The Johns Hopkins University, Baltimore, MD, USA, 2 Harvard University, Cambridge, MA, USA, 3 St. Jude Children’s Research Hospital, Memphis, TN, USA, 4 University of North Carolina Project–Malawi, Lilongwe, Malawi, 5 Malawi Coll of Med–Johns Hopkins Univ Rsr Proj, Blantyre, Malawi, 6 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 7 KwaZulu-Natal Research Institute for TB and HIV, Durban, South Africa, 8 University of Zimbabwe, Harare, Zimbabwe, 9 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 10 National Institute of Child Health and Human Development, Bethesda, MD, USA, 11 FHI 360, Durham, NC, USA, 12 University of California Los Angeles, Los Angeles, CA, USA Background: As use of lifetime ART becomes universal, longer term safety evaluation of extended treatment remains important. This analysis compares rates of clinical and safety events between women randomized to continue or discontinue ART after cessation of breastfeeding (BF) in the PROMISE multi-site PMTCT trial. At the time, lifelong ART was recommended only for symptomatic HIV-infected women with lower CD4 counts. Methods: Women with CD4 counts >350 cells on ART for PMTCT were randomized after cessation of BF to 1 of 2 arms: continue ART or discontinue ART and resume when needed for their own health. Lopinavir-ritonavir + Emtricitabine-Tenofovir was the preferred regimen. Data collected from November 2011 to July 2015 were analyzed. The primary efficacy endpoint was a composite measure of progression to AIDS-defining illness (WHO stage IV clinical event) and/or death. Secondary endpoints included selected clinical and laboratory adverse events (AEs). Analyses used the intent-to-treat principle, according to the randomized arm. The log-rank test compared the two arms. Incidence rates were calculated per 100 person-years (PYs) using a quasi-Poisson model with person time as an offset. Results: 557 women [Malawi (33%), Zimbabwe (25%), South Africa (21%), Uganda (13%), India (6%), Tanzania (1%) and Zambia (one woman)] were randomized at end of BF: 289 to continue and 268 to discontinue ART. At time of randomization, median age was 28 years, mean BMI was 23.1 kg/m2, 93% were WHO clinical stage I, and 95% had CD4 >500 cells/mm 3 . Median follow-up was 84 weeks (range: 4-171) and did not differ between arms. The primary and secondary endpoint rates are shown in Table. There were two deaths, one per arm, and no AIDS-defining illnesses. There were higher rates of Grade 3 or 4

140 ART DETECTION AND RESISTANCE DURING VIRAEMIC EPISODES IN PREGNANCY AND BREASTFEEDING Landon Myer 1 , Andrew D. Redd 2 , Elton Mukonda 1 , Briana Lynch 2 , Tamsin K. Phillips 1 , Anna Eisenberg 2 , Allison Zerbe 3 , Autumn Breaud 4 , Nei-Yuan M. Hsiao 5 , Craig Martens 2 , Maia Lesosky 1 , James A. McIntyre 6 , William Clarke 4 , Elaine J. Abrams 3 , Steven J. Reynolds 2 1 University of Cape Town, Cape Town, South Africa, 2 NIAID, Bethesda, MD, USA, 3 ICAP at Columbia University, New York, NY, USA, 4 Johns Hopkins University, Baltimore, MD, USA, 5 National Health Laboratory Service, Cape Town, South Africa, 6 Anova Health Institute, Johannesburg, South Africa Background: Viremic episodes (VE) following initial viral suppression (VS) occur frequently in HIV+ women initiating ART in pregnancy, particularly postpartum. However the contribution of ART non-adherence vs pre-existing drug resistance mutations (DRM) to VEs in African settings is unknown. Methods: In a South African cohort recruited during routine primary care, HIV+ women initiated TDF+FTC+EFV regardless of clinical stage or CD4 and were followed with intensified VL testing from first antenatal visit through 12m postpartum. In women who achieved VS<50 cps/mL, we conducted a nested case-control study comparing antiretroviral (ARV) drug levels and DRM in: (i) women with VE>1000 cps/mL after initial VS (cases), versus (ii) women who maintained VS (controls; matched on duration of ART use). Plasma from cases (both at time of VE and preceding specimen with VS) and controls were analyzed for the presence of ARV using high-performance liquid chromatography with high-resolution mass spectrometry (Q Exactive; Thermo Scientific; lower limit, 10ng/mL). Viral RNA from VE (cases only) and pre-ART specimens (cases and controls) was amplified and sequenced in the Pol region using next-generation sequencing; consensus sequences encompassing a cluster of at least 0.2% of the total sequences for that sample were included (Illumina Inc). DRM were defined for sequences found in >5% of total consensus sequences.

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CROI 2018