CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

PBMCs for quantitative HIV DNA are collected at most visits. At 84 weeks, qualitative DNA PCR testing is repeated on PBMCs from a 3mL sample, and dual enzyme linked immunosorbent assay (ELISA) is performed (Bio-Rad GS HIV 1/2, Murex HIV 1.2.O). Children starting ART at age 30-365 days in the Botswana ART program and sampled 24-36 months of age served as controls. Results: Between April 2015 and September 2017, 27 HIV+ children enrolled in EIT; 9 had reached 84 weeks on ART. Among these 9 children, median age at ART start was 2 days after birth (range 1, 5), and median baseline HIV RNA was 3145 copies/mL (range < 40, > 10,000,000). By 24 weeks, 6 (67%) had HIV RNA < 40 copies/mL; 5 (56%) remained < 40 copies/mL at all subsequent visits through 84 weeks. At the 84-week visit, 8 (89%) were < 40 copies/ mL. HIV ELISA was negative in 5 (56%) children at week 84 (all were children with low or undetectable HIV RNA from 24-84 weeks); indeterminate in a child with subsequent viral rebound at week 96; and positive in 3 children with high HIV RNA at ≥ 24 weeks. Qualitative HIV DNA PCR at 84 weeks had reverted to negative for 6 (67%) of the early treated children, but only 2 (12%) of 17 controls. Figure 1 shows quantitative HIV DNA levels in PBMCs from enrollment through 84 weeks, with a median of 94.5 copies/million PBMCs at enrollment and 5.3 copies/million PBMCs at the week 84 visit. In the 6 children with negative qualitative DNA PCRs, 4 (67%) had quantitative HIV DNA PCR ≤ 5 copies/million PBMCs, and 5 (83%) were ELISA negative. Conclusion: Children treated in the first week of life had low HIV viral reservoir at enrollment and after 84 weeks of ART. Negative qualitative HIV DNA PCR at week 84 was accompanied by negative HIV ELISA in 5 of 6 children.

to rebound was 1.8 (range: 0.9-13.1) months. One child (ART-40W) maintained viral suppression until last VL available. Five children were censored due to ART restart. In univariable analysis, among baseline demographic and clinical factors, CD4%was the strongest predictor of longer time to rebound based on the log likelihood ratio. In multivariable analysis, longer time to rebound was associated with higher birth weight, baseline CD4% and viral suppression within 40 weeks of ART start (Table). There was no evidence of significant effect of gender, baseline VL and CD8%, CDC stage, PMTCT, age at ART initiation (6-12weeks) and length of therapy (arm) or site. Sensitivity analyses produced similar results. Conclusion: Most children rebounded by 13 months while one remained suppressed until the end of follow up. Age at ART initiation ranging from 6 to 12 weeks and length of therapy were not associated with longer time to rebound. Our findings may inform the design of clinical trials involving analytic treatment interruption in paediatric HIV.

Oral Abstracts

138 SIMILAR CLINICAL OUTCOMES BETWEEN FORMULA AND BREASTFEEDING WOMEN IN PROMISE

Risa M. Hoffman 1 , Konstantia Angelidou 2 , Sean Brummel 2 , Friday Saidi 3 , Dingase E. Dula 4 , Vidya Mave 5 , Lee Fairlie 6 , Gerhard Theron 7 , Moreen Kamateeka 8 , Tsungai Chipato 9 , Avy Violari 10 , Nahida Chakhtoura 11 , Judith S. Currier 1 , Mary Glenn Fowler 12 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Harvard University, Boston, MA, USA, 3 University of North Carolina Project–Malawi, Lilongwe, Malawi, 4 Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre, Malawi, 5 BJGMC Clinical Trials Unit, Pune, India, 6 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 7 Stellenbosch University, Cape Town, South Africa, 8 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 9 University of Zimbabwe, Harare, Zimbabwe, 10 Perinatal HIV Research Unit, Soweto, South Africa, 11 NIH, Bethesda, MD, USA, 12 The Johns Hopkins University, Baltimore, MD, USA Background: There are mixed data on the relationship between breastfeeding (BF) and disease progression in HIV-infected women. PROMISE 1077HS showed low rates of serious clinical events in formula-feeding (FF) women regardless of whether they continued or discontinued ART postpartum. We present clinical outcomes of predominately BF women in PROMISE 1077BF/FF and examine disease progression rates in light of those previously reported in FF women in 1077HS. Methods: In PROMISE 1077BF/FF, HIV-infected women with pre-ART CD4 cell counts 350 cells/mm 3 who started ART during pregnancy were randomized to continue (cART) or discontinue (dART) treatment after delivery. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. LPV/RTV with TDF/FTC or ZDV/3TC were the preferred study regimens. The primary efficacy endpoint was a composite of progression to AIDS-defining illness (WHO Stage 4 clinical event) or death. Log-rank tests and Cox regression models estimated treatment effects. Incidence rates were calculated per 100 person-years (PYs). A post-hoc analysis evaluated WHO Stage 2 and 3 events. All analyses were intent to treat. Results: 1612 women from 15 sites were enrolled (June 2011-October 2014) and 95%were breastfeeding. Median age at entry was 26 years, CD4 count 698 cells/mm 3 and the majority of women were Black African (97%) and enrolled from South Africa (32%), Malawi (28%), and Zimbabwe (19%). After a median follow-up of 1.6 years, there was no statistically significant difference in disease progression between arms (HR: 0.55; 95%CI 0.14, 2.08, p=0.37). WHO Stage 2 and 3 events were reduced with continued ART (HR: 0.60; 95%CI 0.39, 0.90, p=0.01). The arms did not differ with respect to the rate that women experienced a grade 2, 3 or 4 safety event (p=0.61). Rates of the primary

137 TIME TO VIRAL REBOUND AFTER STOPPING ART IN CHILDREN TREATED FROM INFANCY IN CHER Avy Violari 1 , Man Chan 2 , Kennedy N. Otwombe 1 , Ravindre Panchia 1 , Patrick Jean-Philippe 3 , Diana Gibb 2 , Mark Cotton 4 , Abdel Babiker 2 1 Perinatal HIV Research Unit, Soweto, South Africa, 2 University College London, London, UK, 3 NIAID, Bethesda, MD, USA, 4 Stellenbosch University, Cape Town, South Africa Background: We investigated factors associated with time to viral rebound in children in CHER who started ART at age <12 weeks and received 40 (ART-40W) or 96 weeks (ART-96W) of primary therapy. Methods: HIV RNA viral load (VL) from stored samples was assessed 8 weeks after interruption and 12 weekly thereafter. Included were children with VL<400 c/ml at interruption and ≥1 VL measurement within 12 months. Multivariable stepwise Cox regression models (backwards elimination, exit probability p=0.05) were used to identify factors associated with time to viral rebound (confirmed VL≥400 c/ml). Follow-up was censored at ART reinitiation (if VL had not rebounded) or last VL measurement. Results: Of 183 children virally suppressed (VL<400) at interruption, 54% were from ART-40W and 61%were female. At enrolment, 81% received PMTCT, 81% had CDC stage N; median [IQR] birth weight was 3 [2.7,3.3]Kg. At ART start, median [IQR] age was 1.8 [1.5,2.1] months, CD4% 34 [29,40]%, CD4 count 1982 [1445,2745], CD8% 28 [22,34]% and VL 750000 [376000,750000] copies/ml. Median VL at rebound was 354615 [91040,750000] copies/ml, not significantly different between arms [ART-40W=418760; ART-96W=325000 copies/ml; P=0.19]. 86% of children suppressed within 40 weeks of ART start [88% ART-40W; 83% ART-96W; P=0.38]. Overall estimated cumulative probability of rebound (95% CI) at 2, 4, 6 and 8 months were 70% (63,76)%, 80% (74, 85)%, 94% (90,97)% and 99% (96,100)%, respectively. Median time

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CROI 2018