HIV and Pregnancy

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HIV and Pregnancy Jessica Yager, MD, MPH Clinical Associate Professor of Medicine Division of Infectious Diseases SUNY Downstate Health Sciences University 1 Disclosures "This program is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $3,879,101 with zero percentage financed with nongovernmental sources. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS or the U.S. Government." 2 Albany Medical College endorses the standards of the Accreditation Council for Continuing Medical Education (ACCME) and the guidelines of the Association of American Medical Colleges (AAMC) that the sponsors of continuing medical education activities, speakers and planning committee members of these activities disclose relationships with commercial interests. Commercial interests are defined as any entity producing, marketing, reselling or distributing health care goods or services consumed by, or used on patients. Relationships include receiving from a commercial company research grants, consultancies, honoraria and travel, or other benefits or have a self-managed equity interest in a company. Albany Medical College has implemented a mechanism to identify and resolve all conflicts of interest prior to the educational activity being delivered to learners. Disclosure of a relationship is not intended to suggest or condone bias in any presentation, but is made to provide participants with information that might be of potential importance to their evaluation of a presentation. Disclosures None. 4 The following planning members have no financial relationships to disclose: Cynthia Miller, MD, Sarah Walker, MS and Jennifer Price. Learning Objectives Discuss factors influencing perinatal HIV transmission Describe strategies for reducing the risk of perinatal HIV, based on the U.S. Department of Health and Human Service's Guidelines List at least two recommendations for postpartum follow-up of women living with HIV Describe when and how to consult with and refer patients to providers for more specialized care 6 6 Pre-test Question A 28 yo woman is newly diagnosed with HIV and comes to seeyou for an initial medical visit. She previously used IV heroin, and both shared needles and exchanged sex for heroin; she believes she was infected through shared needles or heterosexual sex. She has now been sober for 4 years, but had delayed getting an HIV test out of fear of the results. She is newly married and would like to start a family though not immediately. Her husband has been tested and is HIV negative. All of the below are true EXCEPT: She should start on ART and achieve a suppressed viral load prior to attempting to conceive You fully anticipate that she will deliver an HIV-negative baby if her viral load remains suppressed throughout her pregnancy and delivery. She should be screened for Hepatitis C. DTG is absolutely contraindicated as part of her ART regimen. Even if her viral load is suppressed at the time of delivery, it is recommended that she not breastfeed if she can exclusively formula feed. 7 Question: Prior to the routine use of combination antiretroviral therapy (cART), what percentage of pregnant woman living with HIV delivered babies who were HIV positive? 10% 25% 50% 75% 100% 8 Why significant? Similar route of transmission of HIV and pregnancy! Historic rates of MTCT 25-35% without intervention Acute HIV infection during pregnancy particularly dangerous to fetus Routes of mother-to-child transmission In utero During labor breastfeeding Background: HIV Natural history: An P, Winkler CA. Trends in Genetics 2010;26:119-131. Background: ACTG 076 Connor EM, Sperling RS, Gelber R et al. N Engl J Med 1994;331:1173-1180 67.5% relative risk reduction Background: ACTG 076 Garcia PM, Kalish LA, Pitt J et al. NEJM 1999;341:394-402. Garcia PM, Kalish LA, Pitt J et al. NEJM 1999;341:394-402. Garcia PM, Kalish LA, Pitt J et al. NEJM 1999;341:394-402. Background: ACTG 076 Working with an HIV-positive female: Ensuring VL<20 Ensuring she is on a tolerated ART regimen without known teratogenicity General pre-natal counseling: etoh, tob reduction/cessation and prenatal vitamins! Working with an HIV-negative partner: Opportunity for PrEP Planning Pregnancy: Serodiscordant family planning: HIV-negative female with an HIV-positive male U=U: Ensure positive male has HIV VL<20 copies/mL PrEP! Planning Pregnancy: ART indicated for all pregnant women Test and counsel as you would any other HIV+ patient Baseline genotype as with any other patient Care of the Pregnant woman with HIV: ART nave Initiating ART in an ART-Nave Pregnant Woman https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Pe... (Updated April 2020) Initiating ART in an ART-Nave Pregnant Woman https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Pe... (Updated April 2020) Dolutegravir and Pregnancy https://aidsinfo.nih.gov/news/2109/recommendations-regarding-the-use-of-... Dolutegravir in Pregnancy https://aidsinfo.nih.gov/news/2109/recommendations-regarding-the-use-of-... Dolutegravir in Pregnancy 25 Zash R, Holmes L, Diseko M et al. N Eng J Med 2019; 381:827-840. 26 https://www.niaid.nih.gov/news-events/newer-anti-hiv-drugs-safest-most-e... AUC reduced 38-39% AUC reduced 26% Darunavir concentrations in pregnancy: Stek A, Best BM, Wang J et al. J Acquir Immune Defic Syndr. 2015 September 1; 70(1): 3341. Highly variable raltegravir pharmacokinetic parameters during pregnancy, including trough levels However, persistent virologic suppression: 92% had VL<400 copies/mL at delivery High placental transfer, with median cord blood RAL levels higher than maternal levels at delivery Raltegravir in Pregnancy Figure 1. Median raltegravir concentration-time curves Watts DH, Stek A, Best BM. J Acquir Immune Defic Syndr. 2014 December 1; 67(4): 375381. Initiating ART in an ART-Nave Pregnant Woman https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Pe... Initiating ART in an ART-Nave Pregnant Woman https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Pe... Women trying to conceive: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Pe... Pill burden and dosing schedule can patient tolerate BID dosing? Gestational age urgency of achieving virologic suppression Side effects fatigue, nausea/vomiting Hypotheses about potential resistance partner's regimen/resistance known? Drug-drug interactions Considerations when initiating a regimen: A Pregnant woman already on ART https://aidsinfo.nih.gov/guidelines/html/3/perinatal/157/pregnant-women-... Monitor CD4 and VL at initial pregnancy visit At least every 3 months (once every trimester), though can consider every 6 months for CD4 if individual has robust immune system and has been stable on regimen for prolonged period At 34-36 weeks to inform decisions about delivery Perform genotype prior to initiating therapy if ART-nave and no prior, and if failing therapy Glucose tolerance test as normal (can consider earlier if on PI) Early US to determine/confirm gestational age and assist in planning possible c-sxn Perform amnio only after stable on ART Monitoring pregnant women with HIV Question: Based on current guidelines, a woman and her provider should plan for a c-sxn delivery if her HIV viral load is: 1. At all detectable (>20 copies/mL) 2. >500 copies/mL 3. >1000 copies/mL 4. >10,000 copies/mL 35 If VL>1,000 near delivery: Plan for c-sxn at 38 weeks Administer IV AZT If a woman presents in labor with unknown HIV-status: Conduct a rapid test If positive: send confirmatory and initiate therapy with IV AZT (mother) and combination ART (infant), to continue for at least 6 weeks Intrapartum and neonatal care Continue ART! Breastfeeding contraindicated Counseling on birth control, family planning Ensure ongoing linkage to care difficult transition period Close ongoing care coordination between HIV, OB, and pediatric providers Postpartum care: mother Consideration of HBV coinfection: Ensure all pregnant women screened for HBV If negative: vaccinate! If positive: Ongoing screening for liver toxicity Ensure on double treatment (NRTI backbone) Test and vaccinate as needed against HAV Baby to receive HBIG and vaccination upon delivery (within 12 hrs) Hepatitis B Hepatitis C MTCT 5-15%. Higher rates in co-infected women with uncontrolled HIV If possible: treat HCV prior to pregnancy Treatment for HCV not recommended during pregnancy Impact of pregnancy on HCV: higher incidence of intrahepatic cholestasis of pregnancy (Wijarnpreecha K et al. Clin Res Hepatol Gastroenterol. 2017;41(1):39-45.) Test and vaccinate against HAV and HBV Screen for liver toxicity Breastfeeding is not contraindicated if mono-HCV infection Infants born to HIV/HCV+ mothers should be Ab screened at 18mos old; need 2 HCV RNA tests if positive 39 Patients with a complicated history of ART resistance, non-adherence Significant psycho-social barriers to care Significant side effects to medications Inability to assist with close coordination of care Assistance of OB and/or pediatric ID specialist When to refer? Post-test Question A 28 yo woman is newly diagnosed with HIV and comes to seeyou for an initial medical visit. She previously used IV heroin, and both shared needles and exchanged sex for heroin; she believes she was infected through shared needles or heterosexual sex. She has now been sober for 4 years, but had delayed getting an HIV test out of fear of the results. She is newly married and would like to start a family though not immediately. Her husband has been tested and is HIV negative. All of the below are true EXCEPT: She should start on ART and achieve a suppressed viral load prior to attempting to conceive You fully anticipate that she will deliver an HIV-negative baby if her viral load remains suppressed throughout her pregnancy and delivery. She should be screened for Hepatitis C. DTG is absolutely contraindicated as part of her ART regimen. Even if her viral load is suppressed at the time of delivery, it is recommended that she not breastfeed if she can exclusively formula feed. 41 HIV - HCV - PrEP - PEP Clinical Consultations For Providers in Upstate NY Call or E-mail for a consultation: 518-262-6864 Monday Friday 8:00 a.m. 4:30 p.m. [email protected] If you have experienced an occupational exposure such as a needle stick, please call 518-262-4043. You will be given an opportunity on the telephone menu to speak to a physician 24 hours a day. www.amc.edu/hiv