CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

was used to evaluate associations and Kruskal Wallis test to compare infant HIV RNA by maternal ART regimen. Results: Among 40 mother-infant pairs, 35 (87.5%) women and 39 (97.5%) infants had a detectable HIV RNA at a median of 2 days post-delivery (range 1, 5 days). Median enrollment HIV RNA was 11,335 copies/ml (range <40, >1,000,0000 copies/ml) for infants and 24,789 copies/ml (range <40, 491,512 copies/ml) for women. Fourteen (35%) enrolled infants were not exposed to any ART in utero, 14 (35%) were exposed to EFV-based ART, 10 (25%) to DTG-based ART, and 2 (5%) to LPV/r-based ART. Median duration of in utero ART exposure was 2.5 weeks (range 0, 40 weeks). Maternal HIV RNA had a strong positive correlation with infant pre-treatment HIV RNA (rs = 0.63, p < 0.001) (Table 1). The duration of ART exposure in utero did not correlate with infant HIV RNA (rs= -0.039, p = 0.81). The median HIV RNA values for infants with either no ART exposure, exposure to EFV, or exposure to DTG were 19,246 copies/mL, 2,491 copies/mL, and 346 copies/mL, respectively; this difference was non-significant (p=0.19), although small numbers were available for these comparisons. Conclusion: Higher maternal HIV RNA post-delivery correlated with higher pre-treatment infant HIV RNA. Effective ART to reduce maternal HIV RNA in pregnancy may also reduce viral burden among infants with in utero HIV acquisition, beginning the beneficial early treatment process and potentially reducing viral reservoir.

(p<0.001) and the change in HIV-1 DNA during interruption (p<0.01) were independent significant predictors of slower subsequent HIV-1 DNA decay. In contrast, children who received prolonged initial treatment for 96 weeks had a faster decay after reinitiating than those interrupting after 40 weeks (p=0.02). Conclusion: Rapid HIV-1 DNA decay in very early treated children suggests that ART can prevent persistence of long-lived infected cells. Delaying or interrupting ART is associated with longer persistence of infected cells. Further studies are needed to study the unintegrated fraction of HIV-1 DNA in early treated children, the proportions of integrated proviruses that are defective or intact; and InSTI-containing regimens.

Poster Abstracts

799LB VIROLOGIC RESPONSE TO VERY EARLY ART IN NEONATES WITH IN UTERO HIV: IMPAACT P1115 Deborah Persaud 1 , Ellen G. Chadwick 2 , Camlin Tierney 3 , Bryan Nelson 3 , Mark Cotton 4 , Anne Coletti 5 , Theodore Ruel 6 , Mutsa Bwakura-Dangarembizi 7 , Macpherson Mallewa 8 , Kimesh L. Naidoo 9 , Christina Reding 10 , Rohan Hazra 11 , Patrick Jean-Philippe 12 , Yvonne Bryson 13 , for the IMPAACT P1115 Study Team 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA, 3 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 4 Stellenbosch University, Stellenbosch, South Africa, 5 FHI 360, Durham, NC, USA, 6 University of California San Francisco, San Francisco, CA, USA, 7 University of Zimbabwe, Harare, Zimbabwe, 8 University of Malawi, Blantyre, Malawi, 9 CAPRISA, Durban, South Africa, 10 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 11 National Institute of Child Health and Human Development, Bethesda, MD, USA, 12 NIH, Bethesda, MD, USA, 13 University of California Los Angeles, Los Angeles, CA, USA Background: Perinatal HIV infection treated ≤48 hours of birth (very early ART [VE-ART]) limited HIV reservoirs and provided 27 months of undetectable viremia off ART in the “Mississippi baby”. IMPAACT P1115 is an ongoing prospective phase I/II proof-of-concept study of VE-ART of in-utero infected infants. We report on the completed viral load (VL) response and safety follow- up through 52 wks. Methods: Newborns enrolled into two cohorts (Fig.1). Cohort 1 (N=440) was treated within 48 hrs of life (Step 1) due to high-risk HIV exposure from untreated maternal infection. 34 had confirmed infection and moved to Step 2. Cohort 2 (N=20) received non-Study triple ARVs ≤48 hrs of life, and directly enrolled into Step 2 with confirmed infection before age 10 days. LPV/r was added to the Step 2 regimen at 42 wks postmenstrual age and NVP stopped with specified virologic criteria (Fig.1). VL was frequently monitored (Fig.1). Virologic failure (VF) was defined as VL ≥200 cp/mL at wk 24, and confirmed VL≥ limit of detection (LOD) at later visits. Probabilities (95% CI) of sustained viral suppression (no VF) were estimated by Kaplan-Meier method. Grade 3 and 4 safety events were assessed for relation to Study ART. Median (Q1, Q3) are presented.

798 EARLY ART START IN CHILDREN IS ASSOCIATED WITH MORE RAPID DECAY OF HIV-1 DNA Kirsten A. Veldsman 1 , Anita Janse van Rensburg 1 , Shahieda Isaacs 1 , Shalena Naidoo 1 , Barbara Laughton 1 , Carl Lombard 1 , Mark Cotton 1 , John W. Mellors 2 , Gert U. van Zyl 1 1 Stellenbosch University, Parow, South Africa, 2 University of Pittsburgh, Pittsburgh, PA, USA Background: There is limited information on whether the age at ART initiation, duration of the initial treatment phase and subsequent ART interruption influences the persistence of HIV-1 infected cells in children. Methods: We investigated HIV-1 DNA decay in 3 groups of children on ART (ART regimens excluded InSTIs): group-1 were 7 starting at a median of 4 days of life and continuing uninterrupted; group-2 were 8 starting at a median of 5 months and continuing uninterrupted; and group-3, 23 on ART from a median of 1.8 months for either 40 or 96 weeks, then interrupting ART for a median of 7 months, and restarting based on CD4 criteria. Total HIV-1 DNA was assayed with a sensitive HIV-1 subtype C adapted quantitative PCR for a conserved integrase sequence. Goodness of fit of the decay curves within each group was assessed with conditional R². Duration of treatment was square root transformed to fit with the observed deceleration in decay rate. For each group, the point estimates of decay rates were determined at 6 months on continuous ART or 6 months after reinitiating ART. For groups-2 and 3 combined (n=31) a mixed effect regression model was used to investigate covariates of decay rate; with the square root of time, baseline variables and prior interruption as fixed effects, and patient as the random effect. Results: The conditional R² (95% CI) values for the HIV DNA decay curve was 0.82 (0.65-0.93) for group-1 (early start), 0.85 (0.67-0.94) for group-2 (late start) and 0.79 (0.68-0.86) for group-3 (interrupted). At 6 months on continuous suppressive ART: the HIV-1 DNA t½ in months (95% CI) was shorter in group-1; 2.7 (2.1-3.8), compared to 9.2 (7.4-12.1) in group-2; and 9.6 (7.6-12.6) in group-3 (Figure). In the multivariable model, HIV-1 DNA concentration before treatment

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