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Breastfeeding in HIV

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Project ECHO - UNM HIV TeleECHO Clinic Breastfeeding in HIV August 17, 2021 PGY-2 Pharmacy Resident, UNM Truman Health Services Monica Douglas, PharmD 1 Conflict of Interest Disclosure Statement Speaker has nothing to disclose. This presentation was reviewed by UNMHSC and SCAETC faculty to ensure it meets Continuing Education guidelines. This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS). Under grant number U1OHA33225 (South Central AIDS Education and Training Center). It was awarded to the University of New Mexico. No percentage of this project was financed with non-governmental sources. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. 2 Learning Objectives Describe the risk of HIV transmission via breastmilk Recognize factors influencing decisions to breastfeed and recommendations for women with HIV Identify risk reduction strategies in women with HIV who choose to breastfeeding 3 Breastfeeding in HIV Breastfeeding contributes to risk of perinatal HIV transmission Risk of transmission from breastfeeding is 15-20% over 2 years Without maternal antiretroviral therapy (ART) and infant antiretrovirals (ARV) Effective ART significantly reduces, but does not eliminate the risk of transmission via breastmilk PROMISE Trial HPTN 046 Study DHHS HIV Perinatal Guidelines 2021. Nduati R. JAMA 2000; 283(9): 1167-74. 4 DHHS Guidelines: Counseling and Managing Women with HIV in the United States Who Desire to Breastfeed Maternal ART does not eliminate risk of transmission via breast milk Feeding alternatives readily available Lack of safety data Medication adherence challenges postpartum DHHS HIV Perinatal Guidelines 2021. Tuthill EL. J Int AIDS Soc. 2019; 22(1):e25224. Breastfeeding is NOT recommended for women with HIV in the United States 29% of providers (n=93) reported caring for a patient who breastfed despite recommendation 5 WHO Guidelines: Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring Most effective way to reduce transmission is to reduce maternal viral load Breastfeeding should only stop once a nutritionally adequate and safe diet can be provided WHO HIV Guidelines 2021. Mothers with HIV should breastfeed for at least 12 months and may continue for up to 24 months or longer while being fully supported for ART adherence 6 Decision to Breastfeed Patient Considerations Access to feeding alternatives Social, familial, and personal pressure to breastfeed Fear of disclosing HIV status Moseholm E. J Intern Med. 2020; 287:19-31. WHO HIV Guidelines 2021. 7 Decision to Breastfeed Patient Considerations Maternal benefits: Promotes weight loss, decreased risk of postpartum depression, production of oxytocin and prolactin Lowers risk for hypertension, type 2 diabetes, ovarian and breast cancer Infant benefits: Protection against infections and noncommunicable diseases (ex. asthma, allergies) Improved overall survival and development Additional benefits: Emotional bonding, reduces food insecurity CDC Breastfeeding 2021. WHO HIV Guidelines 2021. 8 Decision to Breastfeed Potential Risks HIV transmission via breastmilk Cell-associated viral transmission Transmission despite undetectable plasma viral load Drug toxicity in neonate ARV drug resistance in neonate DHHS HIV Perinatal Guidelines 2021. 9 HIV Transmission via Breastmilk PROMISE Trial Randomized, open-label strategy trial in HIV-1 infected women (not on ART) with CD4 counts 350 cells/mm3 and their HIV-1 uninfected newborns in 7 countries Randomized at 6-14 days postpartum to maternal ART (mART) or infant nevirapine (iNVP) prophylaxis Prophylaxis continued until 18 months after delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity (whichever occurred first) 2431 mother-infant pairs; median CD4: 686 cells/mm3 Infant HIV-infection: 7/1219 (0.57%) in mART vs. 7/1211 (0.58%) iNVP group (HR 1.0, 96% repeated CI 0.3-3.1) Flynn PM. J Acquir Immune Defic Syndr. 2018; 77(4):383-392. 10 HIV Transmission via Breastmilk PROMISE Trial Secondary Analysis 7 infant HIV-1 infections in each treatment arm Median maternal viral load (MVL): mART 6,627 copies/mL vs. iNVP 59,816 copies/mL Two notable cases of MVL "non-detected" or "detected but below 40 copies/mL" on same date of infant's first positive HIV RNA Baseline MVL and CD4 count not significantly associated with infant HIV-1 infection Significantly associated with infant HIV-1 infection: Time-varying MVL in mART arm (HR 13.96; 95% CI 3.12, 62.45) Time-varying CD4 cell counts in mART arm (HR 0.18; 95% CI 0.03, 0.93) Flynn PM. J Acquir Immune Defic Syndr. 2018; 77(4):383-392. 11 Cell-associated HIV Transmission Cell-associated HIV: transmission via latent reservoir Typically measured by HIV DNA Cells become activated via extravasation or transepithelial migration DHHS HIV Perinatal Guidelines 2021. Moseholm E. J Intern Med. 2020; 287:19-31. 12 Safety of ARV in Neonates Reported levels of ARVs in breastmilk lower than maternal plasma levels BAN Study subgroup analysis Higher exposures of nucleoside/tide reverse transcriptase inhibitors (NRTIs)- zidovudine and lamivudine Lower exposures of non-nucleoside/tide reverse transcriptase inhibitors (NNRTIs)- nevirapine, and protease inhibitors (PIs) - nelfinavir and lopinavir Limited data for integrase inhibitors (INSTI) concentrations in breastmilk Dolutegravir 3% of plasma concentration Davis NL. J Acquir Immune Defic Syndr. 2019; 80(4):467-473. Waitt C. PLoS Med. 2019; 16(9):e1002895. 13 Safety of ARV in Neonates PROMISE Trial iNVP prophylaxis not associated with elevated infant toxicity versus mART (preferred regimen: tenofovir DF/emtricitabine + lopinavir/ritonavir) Flynn PM. J Acquir Immune Defic Syndr. 2018; 77(4):383-392. 14 Support maternal ART adherence Early identification of post-partum depression Monitor maternal plasma viral loads every 1 to 2 months while breastfeeding Identify and treat maternal mastitis and infant thrush Increased risk of transmission via breastfeeding DHHS HIV Perinatal Guidelines 2021. Reducing Transmission Risk: Maternal Considerations 15 Reducing Transmission Risk: Neonatal Considerations Administer at least 6 weeks of ARV prophylaxis with zidovudine and/or nevirapine (NVP) to infants Daily nevirapine most extensively studied prophylaxis in breastfeeding infants HPTN 046 Trial: Evaluation of extended NVP prophylaxis (6 months) 1527 breastfeeding infants born to mothers with HIV-1 in four African countries 54% reduction in transmission at 6 months (1.1% vs. 2.4%) Subgroup analysis of mothers on ART: transmission rate was extremely low (0% relative risk reduction) Coovadia HM. Lancet. 2012; 379:221-8. DHHS HIV Perinatal Guidelines 2021. 16 Additional Considerations Exclusive breastfeeding vs. mixed feeding Exclusive breastfeeding (first 6 months) associated with lower rates of transmission than mixed feeding (breast milk plus other liquid or solid foods) Weaning Rapid weaning (over several days) is not recommended Potential for increased viral shedding into breast milk and an increased rate of transmission Limitation of evidence: studies conducted prior to current ART accessibility in low-income countries Coutsoudis A. Lancet. 1999; 354(9177):471-6. Kuhn L. Sci Transl Med. 2013; 5(181):181ra51. 17 Supporting Informed Maternal Decisions https://www.avert.org/hiv-transmission-prevention/pregnancy-childbirth-b.... https://www.llli.org/update-on-hiv-and-breastfeeding-public/ https://www.thewellproject.org/ 18 Conclusions Current recommendations against breastfeeding for women with HIV are based on high availability of feeding resources in the United States Women with HIV may choose to breastfeed for a variety of reasons Utilizing risk reduction strategies is important to decrease risk of HIV transmission via breastmilk 19 Resources National Clinician Consultation Center http://nccc.ucsf.edu/ HIV Management Perinatal HIV HIV PrEP HIV PEP line HCV Management Substance Use Management Present case on ECHO http://echo.unm.edu [email protected] AETC National HIV Curriculum https://aidsetc.org/nhc AETC National Coordinating Resource Center https://targethiv.org/library/aetc-national-coordinating-resource-center-0 Additional trainings [email protected] www.scaetc.org Find additional TeleECHO sessions in your area: https://echo.unm.edu/locations-2/echo-hubs-superhubs-united-states/ https://hsc.unm.edu/echo/get-involved/join-an-echo/ IDEA Platform: Infectious Diseases Education & Assessment. https://idea.medicine.uw.edu/ AETC National HIV Curriculum: 6 core modules for self study; regularly updated; CME, CNE Hepatitis C Online Curriculum: https://www.hepatitisc.uw.edu/ Hepatitis B Online Curriculum: https://www.hepatitisb.uw.edu/ National STD Curriculum: https://www.std.uw.edu/ 20 References DHHS HIV Perinatal Guidelines 2021. Nduati R. JAMA 2000; 283(9): 1167-74. Tuthill EL. J Int AIDS Soc. 2019; 22(1):e25224. WHO HIV Guidelines 2021. CDC Breastfeeding 2021. Moseholm E. J Intern Med. 2020; 287:19-31. Flynn PM. J Acquir Immune Defic Syndr. 2018; 77(4):383-392. Davis NL. J Acquir Immune Defic Syndr. 2019; 80(4):467-473. Waitt C. PLoS Med. 2019; 16(9):e1002895. Coovadia HM. Lancet. 2012; 379:221-8. Coutsoudis A. Lancet. 1999; 354(9177):471-6. Kuhn L. Sci Transl Med. 2013; 5(181):181ra51.