HIV Infection and Pregnancy Managing Mother and Baby The National Pediatric & Family HIV Resource Center University of Medicine & Dentistry of New Jersey In collaboration with regional AIDS Education & Training Centers With support from the U.S. Centers for Disease Control and Prevention, Cooperative Agreement # R62/CCR217856-02 Scope of the Epidemic Among Women and Children 125,000 AIDS cases in women reported through June 1999 AIDS in women has risen from 7% early in the epidemic to 24% of adult cases today 263 new AIDS cases reported in children in 1999 10,000 – 20,000 estimated children living with HIV infection 300 – 400 babies continue to be born with HIV infection each year in the U.S. Perinatal Transmission of HIV Without antiretroviral drugs during pregnancy, mother-to-child transmission has ranged from 16%–25% in North America and Europe 21% transmission rate in the U.S. in 1994 before the standard recommendations of zidovudine (ZDV) in pregnancy In 1995, transmission rate was 11% after the change in practice USPHS Guidelines for the Use of Antiretroviral Drugs in Pregnant Women for Maternal Health & Prevention of HIV Transmission Developed in 1994 in response to ACTG 076 Working Group reconvened in December 1999 and meets monthly Updated recommendations available online at HIV/AIDS Treatment Information Service web site (www.hivatis.org) Impact of PHS Guidelines for Reducing Perinatal HIV Transmission Perinatal HIV transmission has declined sharply since the USPHS issued guidelines in 1994, resulting in a dramatic decrease in pediatric AIDS cases 4-State Study: Louisiana, Michigan, New Jersey and South Carolina (CDC, 1998) 1993 1996 Women diagnosed before giving birth 68 % 81% Women offered prenatal ZDV 27 % 85 % Women offered intrapartum ZDV 5 % 75 % Infants offered neonatal ZDV 5 % 76 % National Recommendations for HIV Testing of Pregnant Women Universal testing with patient notification as a routine component of prenatal care Institute of Medicine (IOM)–“Reducing the Odds”–1998 American Academy of Pediatrics & the American College of Obstetricians & Gynecologists–Joint Statement–1999 USPHS recommendations are under revision (coming soon) Important: Regulations, laws, & policies about HIV screening of pregnant women vary state to state Routine Counseling and Voluntary HIV Testing of All Pregnant Women Provider Role Include HIV prevention education as part of routine antenatal care Offer HIV testing to all pregnant women Provide information on HIV/AIDS Consider woman’s age, culture, education, and language Routine Counseling and Voluntary HIV Testing of All Pregnant Women Provider Role Document consent /or decision NOT to test Address reasons for not testing and offer again Offer the test again for clinical indications Provide/refer women with risk behaviors for more intensive client-centered prevention counseling Routine Education/Counseling about the HIV Test for Pregnant Women Content: individual counseling, or by brochures, videos, group classes Cause of HIV/AIDS and how it is spread Highly effective treatment is available for the woman’s health and to protect the fetus from acquiring HIV HIV testing is recommended for all pregnant women Services are available to help women from becoming infected and to provide medical care and other assistance to those who are infected Prenatal Messages for Counseling Pregnant Women About the HIV Test Anyone can get HIV infection. Women especially may not know they are at risk HIV is treatable. Treatment can prolong a woman’s life and prevent HIV transmission to her infant during pregnancy Most women who get the HIV test do not have the virus If a woman is HIV+ during pregnancy, she can get treatment immediately Prenatal Messages (continued) If a woman is HIV negative during pregnancy, she can learn ways to prevent getting the infection in the future All information about HIV testing and the results are kept confidential to the extent allowed by law. Results may be reportable in your state Federal and state laws protect women with HIV from discrimination Experts recommend that all pregnant women receive an HIV test regardless of whether a woman thinks she is at risk Counseling the Pregnant Woman with a Positive HIV Test Result Meaning of the positive test results Need for medical management Treatment options for her and/or to reduce perinatal transmission Importance of social support Referral for social services Collaboration between OB, HIV specialist, and the pregnant woman Counseling the Pregnant Woman with a Negative HIV Test Result Explain the meaning of the negative test results Discuss and reinforce risk reduction strategies Teach safer sexual practices to help assure she continues to be HIV negative Acceptance of HIV Testing among Pregnant Women IOM reported 75–86% of pregnant women accepted voluntary HIV testing The IOM reported that evidence demonstrates that pregnant women are likely to accept HIV testing when it is offered Barriers and Supports to Universal Prenatal HIV Testing Provider’s recommendation about testing 92.8% were tested if strongly recommended 42% if clinician had not recommended Private insurance associated with not being tested Reasons for not being tested Not perceiving herself at risk (55.3%) Having been tested recently (39%) Test not offered or recommended (11%) Adverse consequences rarely mentioned Interpreting HIV Test Results Standard: HIV Serology ELISA: enzyme immunoassay (EIA) Initial screening If repeatedly reactive, confirmed by supplemental test (Western blot) Western Blot: confirmatory test Optional Testing Rapid/Expedited Testing: Reactive rapid test MUST be confirmed by a supplemental test Timing of Perinatal HIV Transmission Casesdocumented intrauterine, intrapartum, and postpartum by breastfeeding In utero 25%–40% of cases Intrapartum 60%–75% of cases Addition risk with breastfeeding 14% risk with established infection 29% risk with primary infection Current evidence suggests most transmission occurs during the intrapartum period Breastfeeding and HIV Infection Women with HIV infection in the U.S. should not breastfeed Women considering breastfeeding should know their HIV status Factors Influencing Perinatal Transmission Maternal Factors HIV-1 RNA levels (viral load) Low CD4 lymphocyte count Other infections, Hepatitis C, CMV, Bacterial Vaginosis Maternal injection drug use Lack of ZDV during pregnancy Obstetrical Factors Length of ruptured membranes/chorioamnionitis Vaginal delivery Invasive procedures Infant Factors Prematurity Maternal Viral Load and Risk of Transmission Women & Infants Transmission Study (WITS) HIV-1 RNA Transmission % N <1000 0 0/57 1000 - 10,000 16.6 32/193 10,001- 50,000 21.3 39/183 50,001-100,000 30.9 17/54 >100,000 40.6 26/64 Maternal Viral Load (VL), ZDV Treatment and the Risk of Perinatal HIV Transmission Correlation between high maternal VL and transmission Transmission observed at every VL level, including undetectable levels No HIV RNA threshold below which there was no risk of transmission ZDV decreases transmission regardless of HIV RNA level Initiate maternal ZDV regardless of Recommendation: plasma HIV RNA or CD4 counts What have we learned? Interrupting Perinatal HIV Transmission: Study Results ACTG 076 A phase III randomized placebo-controlled trial of zidovudine (ZDV) for the prevention of maternal-fetal HIV transmission Treatment Regimen Antepartum 100 mg ZDV po 5x day, started at 14 – 34 weeks gestation Intrapartum During labor, 1- hour initial dose 2 mg/kg IV followed by continuous infusion of 1 mg/kg until delivery Postpartum/Infant Regimen 2 mg/kg po q 6 hr for 6 weeks, to start 8 – 12 hours after birth Results of ACTG 076 30 This represents a 66% reduction in risk for transmission (P = <0.001) 20 22.6% Efficacy was observed in all subgroups 10 7.6% Placebo ZDV Group Follow-up of Uninfected Infants in ACTG 076 ZDV versus Placebo No significant difference in growth No difference in CD4 and CD8 counts between groups No other safety abnormalities have been identified No differences in Bayley developmental scores in uninfected infants in ACTG 219 Follow-up of infants with exposure to nucleoside analogues is ongoing due to the potential for mitochondrial toxicity In the U.S. no cases of mitochondrial toxicity have been identified Follow-Up of Women in ACTG 076 Median follow-up 4.2 years No substantial differences in CD4 count, time to progression to AIDS, or death in women who received ZDV compared to those who received placebo Reducing Intrapartum HIV Transmission: Studies of Short Course Therapy Oral ZDV in a non-breastfeeding population (Thailand) from 36 weeks and during labor Transmission rate: 9.4 % ZDV vs 18.9 % placebo Petra study – intrapartum/postpartum oral ZDV/3TC in a breast-feeding population (Uganda, S. Africa,Tanzania) Transmission rate: 10% ZDV/3TC vs 17% placebo HIVNet 012 – intrapartum/postpartum/neonatal nevirapine (NVP) vs short course/neonatal ZDV in a breast-feeding population (Uganda) Transmission rate: 12% NVP vs 21% ZDV Reducing HIV Transmission with Suboptimal Regimens Partial ZDV regimens: (New York cohort) Transmission rates 6.1% with prenatal, intrapartum, and infant ZDV 10% with only intrapartum ZDV 9.3% if only infant ZDV started within first 48 hours 26.6% with no ZDV Treating Women with HIV Infection in Pregnancy Goals of Antiretroviral Therapy To prolong life and improve quality of life To suppress HIV to below the limits of detection or as low as possible, for as long as possible To preserve or restore immune function When Should an Adult be Treated? Clinical Category CD4+ count & HIV RNA Recommendations Symptomatic Any value Treat Asymptomatic CD4+ T cells <200/mm3 Treat HIV RNA any value CD4+ T cells >200/mm3 but Offer treatment if pt <350 /mm3, HIV RNA any value willing to accept Asymptomatic CD4+ T cells >350/mm3, HIV Some experts would RNA >30,000 (bDNA) or treat >55,000 (RT-PCR) CD4+ T cells >350/mm3, HIV Many experts RNA <30,000(bDNA) or <55,000 would delay therapy (RT-PCR) & observe Guidelines for Care of All Pregnant Women with HIV Infection Provide standard clinical evaluation – HIV disease stage Provide standard immunologic evaluation – absolute CD4, CD4% Provide standard virologic evaluation – HIV-RNA copy number (viral load) Discuss known or unknown risks/benefits of therapy during pregnancy Develop strategy for long term evaluation and management of mother/infant Guidelines for Antiretroviral Drugs in Pregnancy: Concepts Use optimal ARV for the woman’s health Add ZDV regimen for reducing perinatal HIV transmission Discuss preventable risk factors for perinatal transmission Counsel on cesarean delivery Support decision-making by woman following discussion of known and unknown benefits and risks Acceptance or refusal of ARV or ZDV should not result in denial of care or punitive action Guidelines for Antiretroviral Drugs in Pregnancy: Clinical Scenario 1 Women without prior antiretroviral therapy: Recommend: Standard combination therapy for women with high viral load, low CD4 count Combination therapy for women with viral load 1,000 regardless of clinical or immunologic status 3-part ZDV regimen to reduce perinatal transmission for all HIV-infected pregnant women, regardless of antenatal viral load Consider delaying therapy until completion of first trimester Offer scheduled cesarean delivery for women with viral loads >1000 (based on most recent VL results) Clinical Scenario 2 Women currently on antiretroviral therapy: Discuss benefits and potential risks of her current regimen during pregnancy Add or substitute ZDV at 14 weeks Recommend intrapartum and neonatal ZDV Discontinue teratogenic drugs Consider continuing or stopping current therapy based on gestational age (<14 weeks) If therapy is stopped, stop and restart all ARV simultaneously Resistance testing for suboptimal viral suppression or failure Clinical Scenario 3 Women with HIV infection and present in labor with no previous treatment: Discuss benefits of treatment during intrapartum and neonatal period Four treatment options Single dose nevirapine for mother at onset of labor followed by single dose of nevirapine for the newborn at age 48–72 hrs Oral ZDV/3TC for mother during labor followed by one week oral ZDV/3TC to the newborn Intrapartum IV ZDV followed by six weeks ZDV for the newborn The two-dose nevirapine regimen as above combined with intrapartum IV ZDV and six week ZDV for the newborn Clinical Scenario 4 Infant whose mother did not receive prenatal or intrapartum ZDV: Offer the six-week neonatal ZDV component Initiate therapy as soon as possible after maternal consent (preferably within 6 – 12 hours of birth) Begin diagnostic testing of the infant Refer to pediatric HIV specialist for long-term care Assessment of the Pregnant Woman with HIV Infection Initial Assessment: Desires Antiretroviral Therapy Yes No Treat according to clinical Monitor for HIV disease & immunologic status progression Recommend ZDV Wants to perinatal transmission Recommend combination therapy if VL >1000 Discuss C/S Follow-Up Assessment of Pregnant Woman with HIV 4 weeks after initiation of treatment, then q 3 months if viral load stable Fetal assessment based on gestational age CD4+ and viral load response New onset of symptoms Side effects or toxicities Adherence to therapy Long-range planning for continuity of medical care Changing HIV Therapy During Pregnancy Poor CD4 response Drugs with potential teratogenicity Poor viral load response Poor adherence to regimen Evidence of viral resistance Cesarean Section to Reduce Perinatal HIV Transmission Pregnant women with VL >1000 should be counseled re: potential benefit of scheduled C/S to reduce perinatal transmission Unknown whether scheduled C/S offers any benefit to women on HAART with low or undetectable VL given the low transmission rate Complications of C/S similar to HIV uninfected women Patient’s decision should be respected and honored Preterm Labor and the Use of Combination Antiretroviral Therapy A Swiss study reported a possible association between combination ARV therapy and preterm births Preliminary review of U.S. cohorts has not supported the association Patients should be educated and cautioned about signs of preterm labor Antiretroviral Pregnancy Registry A collaborative project managed by PharmaResearch Corporation on behalf of an advisory committee (specialists in OB/Gyn, ID, teratology, epidemiology, and CDC and NIH members) and sponsored by: Abbott Laboratories, Agouron Pharmaceuticals, Inc., Boehringer Ingelheim Company, Bristol-Myers Squibb, Co., DuPont Pharmaceuticals Company, GlaxoSmithKline, F. Hoffmann-LaRoche Ltd., Merck & Co., Inc. Purpose: To assess safety of antiretroviral drugs during pregnancy Telephone: (800) 258-4263 Fax: (800) 800-1052 Comprehensive Care of Women Postpartum Primary and HIV specialty care Ob/gyn and family planning services Mental health and substance abuse treatment as needed Coordination of care through case management for the woman and her family Support services for the family Evaluation and Follow up of Infants HIV diagnostic testing to establish or rule-out HIV infection as early as possible Referral to an HIV specialist PCP prophylaxis initiated at 6 weeks of age Long-term follow-up of HIV- and ARV-exposed infants Support services for the family Case Studies Case Study 1 Angela, 41 y.o., first prenatal visit, approximately 19 weeks gestation, tested HIV+ 2 months ago. CD4+ 725, HIV-1 RNA 600 copies/ml. This is her 4th pregnancy, she has no children. What recommendations for antiretroviral therapy apply in this case? What questions will you ask; what options to present? What OB condition may complicate this case? Follow-up after delivery for the woman and infant Case Study 2 Maria, 27 y.o., at 35 weeks gestation, requested HIV test. Former boyfriend died of AIDS. Test is positive, CD4+ 350, HIV-1 RNA 120,000; husband and child test negative. Refuses ZDV. “It made my boyfriend worse.” Wants the cocktail that Magic Johnson uses. What are the recommendations for this woman? Psychological issues? Related to community beliefs? What counseling will you do? Case Study 3 Ellen, 32 y.o., 9 – 10 weeks gestation, tested positive on voluntary prenatal screening. A former heroin user, she is now on methadone. CD4+ 198. HIV-1 RNA is 100,000. Under stress. Wants HAART therapy and a C-section. Wants to know what else she can do to stay well. Heard that ritonavir is a good drug. What are the recommendations for this woman? Screening for other infectious complications? Options for reducing perinatal transmission? What management issues does this case present? Case Study 4 Heather, 14 weeks gestation, HIV+ for 5 years, stage B2 (mild dysplasia), CD4+ 220; HIV-1 RNA is 5,000. She’s on ZDV, ddI and nelfinavir. She’s anemic. Husband has AIDS. This is a planned pregnancy. Office staff feel this couple is “irresponsible” for having a baby. What are the recommendations for this woman? What information does this couple need? What are other options for this woman? Should she be referred? How are you going to deal with the office staff? Case Study 5 Joan, G8P3222, HIV+ for 3 years, admitted with ruptured membranes. No prenatal care. Lost 2 children to HIV. Urine + for cocaine, GB strep + (urine, cervix), other STDs negative. CD4+ 845. What are the recommendations for this mother and infant? How will you present the 076 regimen to this woman? What alternative therapies can she choose to decrease perinatal transmission? What should follow-up care include? Case Study 6 Twelve hours after the birth of her infant, Angela G’s HIV test comes back positive. She tested negative early in her pregnancy but the test was repeated on admission to L & D because she reported that her husband was “back to using IV drugs”. She did not have any antenatal or intrapartum antiretroviral therapy. What are the recommendations for this mother and infant? How will you present the 076 regimen to this woman and what are the options ? What follow-up care is needed for Angela and her baby?
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