CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF at 14-28 weeks of gestation. Matched maternal and infant samples were prospectively collected at random at Week 6 postpartum. Validated liquid chromatography-tandem mass spectrometry assays quantitated plasma and breastmilk concentrations of DTG, TAF, and TFV. The lower limit of quantitation for DTG, TAF, and TFV in breast milk and plasma was 7.8, 0.195, and 0.0977 ng/mL and 9.8, 3.9, and 0.977 ng/mL, respectively. Samples below the quantitation limit (BQL) were imputed to 0. The relative infant dose for each ARV was estimated by assuming an average milk intake of 150 mL/kg/day and each ARV's observed breast milk concentrations. Results: Data were available from 192 postpartum lactating women and their 192 predominantly breastfed infants. The average (SD) age of mothers at enrollment was 26 (6) years old, and most participants (85%) lived in Zimbabwe, Uganda, or Tanzania. Overall, 55% of infants were female with a mean (SD) gestational age of 40 (2) weeks, weight of 3089 (490) grams, and length of 50 (3) cm at birth. Median (range) maternal plasma concentrations of DTG, TAF, and TFV were 2810 (0.0-7460), 0.0 (0.0-158), and 96.1 (0.0-353) ng/mL, respectively. Breast milk (BM) and infant plasma (IP) concentrations are displayed in the Figure. The estimated median (range) relative infant dose of DTG, TAF, and TFV from breastfeeding was 1.92% (0.00-4.89), 0.00% (0.00-0.03), and 0.03% (0.00 0.11), respectively. Conclusion: Breast milk transfer of DTG, TAF, and TFV is low and results in minimal systemic exposure in predominantly breastfed infants. The clinical relevance of subtherapeutic concentrations of these ARVs in breast milk is unknown but should be considered in the context of risk of drug resistance in infants who acquire HIV. 1077BF: Breast Milk Reservoir, Tenofovir Levels, and HIV Transmission Among Breastfeeding Mothers Maxensia Owor 1 , Patricia DeMarrais 2 , Kristin Baltrusaitis 2 , Lisa Frenkel 3 , Brookie Best 4 , Lynda Stranix-Chibanda 5 , Dhayendre Moodley 6 , Avy Violari 7 , Brenda Kakayi 1 , Mary G. Fowler 8 , for the PROMISE 1077 Study Team 1 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of Washington, Seattle, WA, USA, 4 University of California San Diego, San Diego, CA, USA, 5 University of Zimbabwe, Harare, Zimbabwe, 6 University of KwaZulu-Natal, Durban, South Africa, 7 University of the Witwatersrand, Johannesburg, South Africa, 8 Johns HopkinsUniversity, Baltimore, MD, USA Background: Recent studies observed detectable HIV-1 virus levels in breastmilk (BM) despite undetectable HIV-1 RNA viral load (VL) in plasma. This discordance between HIV VL in plasma and BM could account for residual vertical HIV-1 transmission during lactation. We assessed the association of vertical HIV-1 transmission with HIV VL in plasma and BM, and with tenofovir (TFV) drug levels. Methods: This case-control study was nested within the IMPAACT PROMISE 1077BF perinatal HIV trial which evaluated maternal ARV strategies to prevent BM HIV transmission. Cases were mother-infant pairs with infants who had a positive HIV nucleic acid test (NAT) during the breastfeeding period; control pairs had infants who were HIV NAT negative. Two controls were matched for each case by infant sex, study site, maternal age at delivery, and 1077BF component at infection. Maternal plasma and BM collected near an infant's infection date were assayed for HIV total nucleic acid (TNA; DNA + RNA) VL, DNA VL, RNA VL, and TFV concentration. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: 93 mother-infant pairs (31 cases; 62 controls) were enrolled from Malawi, Uganda, South Africa, Zimbabwe and India. Median maternal age at delivery was 25 years, 39 (42%) were male infants, 57 (61%) were randomized in the postpartum component. Median (Q1, Q3) age of infection was 6 (3, 14) months. Over 70% (22/31) of samples were taken on the same day or within one month of infection. Median (Q1, Q3) maternal plasma VL was 39,228 (4822, 124,886) copies/ml for cases vs 20 (20, 2,104) for controls. BM RNA VL was above lower limit of quantification for 17 (55%) cases and 7 (11%) controls. The odds

models were used to identify differentially abundant compounds in breast milk between the infant outgroups among WWH and WWoH. All p-values were adjusted for multiple comparisons using the Benjamini-Hochberg false discovery rate method. Results: 1597/1599 samples were successfully analyzed with identification of 765 known biochemicals and 74 unknown biochemicals. Tryptophan levels were significantly lower in the milk samples of WWH compared to WWoH at all timepoints. Log-transformed kynurenine:tryptophan (KT) ratios were elevated in the milk of WWH at all timepoints (p < 0.001). The KT-ratio at 1 month was correlated with baseline maternal plasma and 1 month breast milk HIV RNA (r2 of 0.28 and 0.20, respectively), and inversely with baseline CD4 count (r2 = -0.32); all p<0.001. Dimethylarginine was elevated in the milk of WWH during the first 9 months of lactation. A novel metabolite, X-12127, was significantly elevated in the milk of WWH at all timepoints following the first week of life (p<0.001 through 12 mos, then p<0.1 at 15 and 18 mos). Conclusion: Tryptophan is significantly lower in the milk of WWH throughout early infancy. As breast milk serves as the only source of this essential amino acid, this depletion likely contributes to the impaired immune development of children born to WWH. Elevations of dimethylarginines may alter nitric oxide levels. Identifying key alterations and novel therapeutics is of critical importance for the one million children born to WWH each year.

Poster Abstracts

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Breast Milk Transfer and Infant Exposures to DTG, TAF, and TFV: Results From IMPAACT 2010/VESTED Tk Nguyen 1 , Jung-Woo Chae 1 , Lauren Ziemba 2 , Anne Coletti 3 , Kevin Knowles 4 , Benjamin Johnston 4 , Patrick Jean-Philippe 5 , Tsungai Mhembere 6 , Tariro Chawana 6 , Deo Wabwire 7 , Violet Korutaro 8 , Shahin Lockman 9 , Lameck Chinula 10 , Jeremiah Momper 1 , for the IMPAACT 2010/VESTED Protocol Team 1 University of California San Diego, La Jolla, CA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 FHI 360 , Lusaka, Zambia, 4 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 5 National Institutes of Health, Bethesda, MD, USA, 6 University of Zimbabwe, Harare, Zimbabwe, 7 Makerere University, Kampala, Uganda, 8 Baylor College of Medicine Children's Foundation, Mbabane, Eswatini, 9 Brigham and Women's Hospital, Boston, MA, USA, 10 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Limited information is available on breast milk transfer and subsequent infant systemic exposure to dolutegravir (DTG), tenofovir alafenamide (TAF), and tenofovir (TFV). We evaluated concentrations of these antiretroviral (ARV) drugs in time-matched samples (maternal plasma, breast milk, and infant plasma) in a post hoc analysis of IMPAACT 2010, a randomized trial that evaluated three ARV treatment regimens in pregnancy. Methods: Pregnant women with HIV in 9 countries were randomized 1:1:1 to start open-label ART with DTG+emtricitabine (FTC)/TAF, DTG+FTC/tenofovir

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