Presentation on theme: "HIV Case Conference Working Toward Elimination of Mother-to-Child Transmission: Practical Aspects for the Perinatal Team Please include the title of your."— Presentation transcript:
1HIV Case Conference Working Toward Elimination of Mother-to-Child Transmission: Practical Aspects for the Perinatal TeamPlease include the title of your presentation, your full name and affiliations (including your role within the AETC, if applicable).Carina Rodriguez, MDFaculty, Florida/Caribbean AETCUniversity of South FloridaThursday, May 8, 2014Time: 2:00 pm-3:00 pm (EDT)
2HIV Case Conference Series Objectives Identify the role, uses, and complications of antiretroviral therapy as a treatment option according to the Department of Health and Human ServicesDescribe the major issues of age and gender appropriate HIV care including management of special populations such as pregnant women, and gay, lesbian or transgender patientsIdentify and treat HIV disease, HIV complications and co-morbid conditions in the primary care settingIdentify and access resources and standard of care protocols that can be immediately applied to any clinical settingDescribe legislation and/or recommendations about HIV testing, confidentiality, access to medical care, post-exposure prophylaxis and pre-exposure prophylaxisIdentify the modes of transmission of HIV and epidemiology of the disease and related infectionsDiscuss strategies to increase the ability of healthcare providers to provide culturally competent care
3Session Specific Objectives Upon completion of this program, participants will be able to:Review current recommendations for the prevention of mother-to-child transmissionLearn virologic and serologic methods for identification of HIV infection, their use in pregnancy and special scenarios, including discordant partners, suspected acute infection and infant testingReview current evidence regarding mode of delivery and risk for infectionLearn current antiretroviral therapies for HIV-infected pregnant women and exposed/infected childrenRecognize clinical scenarios associated with increased risk for transmission and selective antiretroviral therapy/prophylaxis
4Continuing Education Disclosure The following presenter has financial relationships with the following commercial entities to disclose:Carina Rodriguez, MDGrant/Research Support: Gilead, ViiV, Merck, and NICHDThis presenter will not discuss any off-label use or investigational product during the program.
5Continuing Education (Up to 1.0 hours of CE/CME) Suwannee River Area Health Education Center, Inc., is a Florida Board of Nursing, Clinical Social Work, Marriage, Family Therapy, Mental Health Counseling, Dentistry, and Pharmacy approved provider of continuing education. CE Broker Provider ID # This program meets the requirements for up to 5.0 contact hours.Continuing Medical EducationThis activity has been planned and implemented in accordance with the Essentials Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Florida AHEC Network and the Florida/Caribbean AIDS Education and Training Center. The Florida AHEC Network is accredited by the Florida Medical Association to provide continuing medical education for physicians.The Florida AHEC Network designates this live activity for a maximum of 5.0 AMA PRA Category 1 Credits™. Each physician should claim only the credit commensurate with the extent of their participation in the activity.This slide is required for all CME/CE presentations.For questions regarding CE or CME, please contact our Professional Education Manager at or
6Core Marketing Slide:Slide to replace both Slide 4 and 5 (For review, discussion, comments)
7Perinatal guidelines March 2014 Updates in terminologyThe terms “mother-to-child transmission (MTCT)” and “prevention of mother-to-child transmission (PMTCT)” have been replaced with “perinatal transmission” and “prevention of perinatal transmission”Slides are based on most recent recommendations by the Department of Health and Human Services (HHS)Can be accessed at
9Milestones in Perinatal HIV Pediatric AIDS Clinical Trials Group 076Major Achievement in HIV researchShowed administration of zidovudine (ZDV) to pregnant women and their infants could reduce perinatal transmission by 70%Increased HIV testing in pregnancy and combination ARV prophylaxis during pregnancy has reduced perinatal transmission to <2%.Every HIV-infected infant is a sentinel event representing missed opportunities.
10Perinatal HIV/AIDS Cases The use of ZDV in combination with other highly active antiretroviral therapy (HAART) has been accompanied by a decrease in the number of perinatally HIV-infected children and is responsible for the dramatic decline in perinatally acquired HIV/AIDS since 1994.Numerous initiatives have also contributed to the reduction in these cases: provider education, social marketing, and rapid testing in labor and delivery.As a result, significant decreases in annual perinatal HIV-infected births have been observed since 2001.
11Perinatal Transmission Perinatal HIV transmission is the most common route of HIV transmission in children.Since the beginning of the epidemic, cases of AIDS have been reported perinatally – 4986 of those have died.HIV perinatal transmission peaked in to 1650 perinatally infected infants – there were 162 perinatally infected infants in 2010Perinatal HIV transmission is the most
12HIV-Infected Newborns common route of HIV transmission in children.Since the beginning of the epidemic, 9522 cases of AIDS have been reported perinatally – 4986 of those have died.HIV perinatal transmission peaked in 1991 to 1650 perinatally infected infants – there were 162 perinatally infected infants in 2010Per Perinatal HIV transmission is the most common route of HIV transmission in children.Perinatal HIV transmission is the most common route of HIV transmission in children.
15Common risk factors seen in HIV infected infants Maternal Substance UseLate, Minimal or NO Prenatal careMaternal Denial (or Ignoring) their Known HIV diagnosis – refusing HIV testing in pregnancy warrants further investigation/discussionMaternal Mental Health issuesMaternal HIV diagnosis at Labor and Delivery
16Case 123 y/o female with no history of prenatal care presents in labor at outlying hospitalRapid HIV testing done and negativeNormal SVD, no complications2 months later, mom is admitted to substance abuse rehabilitation facility and HIV testing is repeated and positivePediatrician is contacted and performs HIV ELISA that is positivePCP contacts DOH for further adviceInfant DNA PCR and RNA PCRs confirm HIV infectionCould this infection have been prevented?
17Awareness of Serostatus Estimates of Transmission 25%Unaware ofdiagnosis54% of new infectionsPeople living withHIV / AIDS1,039,000 –1,185,000.New sexual infections each year~32,00075% aware of diagnosis46% of new infectionsMarks G et al.AIDS 2006, 20:1447 – 1450.
21Transmission and Mode of Delivery Scheduled cesarean delivery at 38 weeks gestation to minimize perinatal HIV transmission for women with HIV RNA levels >1000 copies/ml or unknown levels near the time of delivery. (AII)Perform cesarean irrespective of administration of antepartum ARV drugsIV ZDV should be administered for 3 hours total prior to scheduled deliveryCesarean sections performed for standard obstetrical indications should be scheduled for 39 weeks gestation
23Intrapartum Care- Unknown HIV status Conduct rapid HIV antibody testing for women in labor with unknown HIV status. (AII)If positive:Perform confirmatory testing ASAPAdminister maternal IV ZDV and infant combination prophylaxis pending results of confirmatory test. (AII)Continue infant prophylaxis for 6 weeks if confirmatory tests are positive (AI); discontinue prophylaxis if confirmatory testing is negativeIf risk factors or symptoms to suspect acute infection that may be missed during window period with serologic testing consider virologic testing
24Acute HIV infectionWhen acute retroviral syndrome is suspected in pregnancy or during breastfeeding, a plasma HIV RNA test should be obtained in conjunction with an HIV antibody test (AII).Repeat HIV antibody testing in the third trimester is recommended for pregnant women with initial negative HIV antibody tests who are known to be at risk of acquiring HIV, are receiving care in facilities that have an HIV incidence in pregnant women of at least 1 per 1,000 per year, are incarcerated, or who reside in jurisdictions with elevated HIV incidence (AII).All pregnant women with acute or recent HIV infection should start a combination ARV regimen ASAP (AI).Baseline genotypic resistance testing should be performed simultaneously with initiation of the combination ARV regimen, and ARV adjusted, if necessary, to optimize virologic response (AIII).Because clinically significant resistance to protease inhibitors (PIs) is less common than resistance to non-nucleoside reverse transcriptase inhibitors in ARV-naive individuals in general, a ritonavir-boosted PI-based regimen should be initiated (AIII).
25Hidden in the DataOf the 136 Infected babies born in Florida from :27% of all mothers who delivered an infected infant did not know they were positive prior to delivery.20% of all mothers who delivered an infected infant contracted HIV during the pregnancy.
29Florida Statutes: HIV Testing Written informed consent is no longer required prior to HIV screening in health care settings (See Exceptions), however the provider needs to document in the medical record (MR) that patient provided verbal consent.Prior to ordering an HIV test, medical providers are required to:Inform patients that an HIV test will be performedProvide information about the testAdvise the patient of their right to decline the HIV testDocument in MR that patient provided verbal consentExceptions when written consent is required:Blood donationHIV testing for insurance or contract purposesRefusal for HIV testing during pregnancy needs to be in writing (testing in pregnancy is through opt-out process on first trimester and weeks)Minors can be tested for HIV without parental consent provided the minor gives informed consent
30Recommendations for Initiating ART: CD4 Count or Clinical Category Recommended for all CD4 counts:CD4 count <350 cells/µL (AI)CD4 count cells/µL (AII)CD4 count >500 cells/µL (BIII)Recommended regardless of CD4 count:Pregnancy (AI)History of AIDS-defining illness (AI)HIV-associated nephropathy (HIVAN) (AII)Hepatitis B (HBV) coinfection (AII)Age >50 years (BIII)Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence.”Patients may choose to postpone ARTProviders may elect to defer ART, based on an individual patient’s clinical or psychosocial factors
31HIV cycle HIV Replication Cycle Steps in the HIV Replication Cycle Fusion of the HIV cell to the host cell surface.HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell.Viral DNA is formed by reverse transcription.Viral DNA is transported across the nucleus and integrates into the host DNA.New viral RNA is used as genomic RNA and to make viral proteins.New viral RNA and proteins move to cell surface and a new, immature, HIV virus forms.The virus matures by protease releasing individual HIV proteins.
35Recommendations for Use of Antiretroviral Drugs during Pregnancy Preferred NRTIs for ARV-naive pregnant women have been expanded to include abacavir plus lamivudine and tenofovir plus emtricitabine or lamivudine in addition to zidovudine plus lamivudine. Preferred protease inhibitors (PIs) for ARV-naive pregnant women remain ritonavir-boosted atazanavir and ritonavir-boosted lopinavir.Alternative PIs include ritonavir-boosted darunavir and ritonavir-boosted saquinavir.Preferred NNRTI for ARV-naive pregnant women is efavirenz, initiated after the first 8 weeks of pregnancy.Nevirapine is the alternative NNRTI for ARV-naive pregnant women.
36Recommendations for Use of Antiretroviral Drugs during Pregnancy Raltegravir has been moved to the Alternative category for ARV-naive pregnant women, for consideration particularly when drug interactions with PI -based regimens are a concern.In addition, some experts may use raltegravir in late pregnancy in women with high viral loadThere is insufficient data during pregnancy for dolutegravir, elvitegravir/cobicistat/tenofovir/emtricitabine fixed drug combination, ritonavir-boosted fosamprenavir, maraviroc, and rilpivirine.
37Adjusted Rate Ratios for Transmission of HIV in Discordant Couples Quinn TC et al. NEJM 1996;335:^ Viral load in blood may not be predictive of genital tract viral load
38Reproductive Options for HIV-Concordant and Serodiscordant Couples HIV-infected partner(s) in HIV-seroconcordant and HIV-serodiscordant couples planning pregnancy attain maximum viral suppression before attempting conception (AIII).Periconception administration of ARV pre-exposure prophylaxis (PrEP) for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission (CIII) Tenofovir disaproxil fumarate/emtricitabine– approved in July 2012 for HIV prevention in individuals at high risk of HIV transmissionPregnancy is not a contraindication to PrEP.
39Postpartum Follow-Up of HIV-Infected Women Decisions about continuing cART after delivery should be made in consultation with a woman and her HIV provider, ideally before delivery (AIII).cART is currently recommended for all HIV-infected individuals to reduce the risk of disease progression and to prevent HIV sexual transmission. Strength and evidence vary by pretreatment CD4 cell count.
40Infant Antiretroviral Prophylaxis All HIV-exposed infants should receive a 6 week course of ZDV prophylaxis (AI)Mother received standard antepartum and intrapartum ARV prophylaxis with suppressed HIV RNA: infant zidovudine aloneMother did not receive optimal antepartum and intrapartum prophylaxis, risk of HIV transmission is higher, and additional infant ARVs may be recommendedInfants born to mothers who did not receive antepartum ARV drugs6 week course of ZDV, plus3 doses of NVP in the first week of life (AI)1st dose at birth2nd dose 48 hours later3rd dose 96 hours after second dose(Begin regimen as soon as possible post delivery)
41Infant Antiretroviral Prophylaxis Infant Zidovudine HIV Prophylaxis DosingAgeDoseDuration≥35 weeks gestation at birth4 mg/kg/dose PO twice dailyIf unable to tolerate oral agents:3 mg/kg/dose IV every 12 hoursBirth through 6 weeksGive first dose as close to the time of birth as possible (preferably within 6 to 12 hours)≥30 to <35 weeks gestation2mg/kg/dose PO or 1.5 mg/kg/dose IV every 12 hours.At age 15 days, increase to 3 mg/kg/dose PO or 2.3 mg/kg/dose IV every 12 hours.<30 weeks gestation2 mg/kg/dose PO or 1.5 mg/kg/dose IV every 12 hoursAt age 4 weeks, increase to 3 mg/kg/dose PO or 2.3 mg/kg/dose IV every 12 hours
42Infant Antiretroviral Prophylaxis Infant Nevirapine HIV Prophylaxis Dosing in addition to ZDV for high risk cases, consult expert in pediatric HIV
43Initial Postnatal Management of the HIV-Exposed Neonate Virologic tests should be performed at (AII)14-21 days,1 (to 2 months), and4 to 6 monthsVirologic tests at birth may be performedIf mother did not have good virologic control during pregnancyIf adequate follow-up can not be assuredIf infant received expanded prophylaxis, repeat PCR testing recommended 2-4 weeks after discontinuation* With two negative testing by 4 to 6 weeks, do not need to initiate Pneumocystis jiroveci prophylaxis
44Infant Antiretroviral Prophylaxis Alternative combination ARV prophylaxis regimens in infants should be made in consultation with a pediatric HIV specialist before delivery, if possible. A 4-week neonatal ZDV chemoprophylaxis regimen can be considered when the mother has received standard cART with consistent viral suppression and there are no concerns related to maternal adherence (BII).
45Diagnostic Testing in Infants Presumptive rule-out of HIV infection2 or more negative virologic testsOne at age ≥14 days and one at ≥1 month; orOne negative virologic test at ≥2 months; orOne negative HIV antibody test ≥6 monthsDefinitive rule-out of HIV infectionOne at ≥1 month; andOne negative virologic test at ≥4 months; or2 negative HIV antibody tests ≥6 monthsDiagnosis of HIV infection2 positive HIV virologic tests (NAAT-HIV-1 DNA or RNA)on separate blood samples (regardless of age)Positive HIV antibody test with confirmatoryWestern blot (or IFA) at age ≥18 monthsSee Guidelines pgs. 7-10
46Strategies for HIV Care Functional CureLatent reservoirReactivation strategy (HDACi, PD-1) and elimination of reservoir cells (vaccine, Immunotherapy)Latent reservLLL;l;oirHAART during acute infectionHIV replicationin tissuesMember of the CD28/CTLA-4 family of T cell regulators (Ishida EMBO 1992)Negatively regulates T cell responses (Freeman J Exp Med 2000)2 known ligands: PD-L1 and PD-L2, mostly expressed by myeloid cells (Freeman J Exp Med 2000, Latchman Nat Immunol 2001)Blocking PD-1 interaction with its ligands restores HIV specific CD4+ and CD8+ T cells (Day Nature 2006, Trautmann Nat Med 2006, Porichis Blood 2011)Early HAART initiation limits the seeding of the HIV reservoir. Subjects starting HAART during Fiebig I stage display undetectable levels of integrated HIV DNAHIV persists in central and transitional memory CD4 T cellsIL-7 therapy restores CD4 T cell numbers but expands the latent reservoir by inducing homeostatic proliferation of latently infected CD4+ T cellsBlockade of the PD-1 pathway constitutes a promising approach to achieve a functional cureHAART optimization (Mega-HAART?)HIV replicationHAART
47Viral reservoirs and their relative contribution to plasma viremia Steady-state levels of plasma viral RNA reflect the cumulative production of virus from the various cellular reservoirs and the turnover of virus-producing cells in those reservoirs. When viral replication is inhibited by HAART, plasma viral RNA decays in four distinct phases, suggesting that the various viral reservoirs are turned over to very different extents as a result of HIV-1 infection. The first phase reflects virus produced predominantly from activated CD4+ T cells. In the second phase, macrophages may be the main source of virus, because the decay characteristics of plasma viremia in this phase approximates the lifespan of the tissue macrophage. Resting (G1) T cells may also contribute to this more slowly turning over reservoir. The third phase reflects an extremely low and chronic production of virus from a stable reservoir. Presumably cells constituting this reservoir maintain a low and sustained output of virus, while simultaneously resisting cytopathic effects and killing by cytotoxic T lymphocytes. Resting CD4+ T cells or DCs may be the sources of virus in this covert reservoir. The fourth phase of decay is based on in vitro measurements of the frequency of latently infected CD4+ T cells, but FDCs harboring trapped virions might also be a long-lived source of infectious virus in this phase.Stevenson, M.Nature Medicine 9, (2003)
48HIV CureBerlin patient – Evidence of cure of HIV following Bone Marrow Transplantation (Two transplants with CCR5 Delta 32 mutation donor)Mississippi Child – Evidence of functional cure of HIV following treatment for HIV within 30 hours of life.nd Infant with HIV seroreversion – treated aggressively within 4 hours of life – remains on antiretrovirals.Clinical trials are planned to address whether administration of a three-drug regimen in therapeutic doses to HIV-exposed high-risk infants could alter the establishment and long-term persistence of HIV infection.
49Unique aspects of HIV infection in pediatrics Unique immunologic characteristics (evolving immunity and immune tolerance)Unique “gut” immunity (relative lack of immune activation in the gut and increased regenerative capacity)Timing and source of infection more easily determined than in adultsPotential limitation of HIV infection prior to establishment of latent reservoirs with early treatment Tobin, N. Curr HIV/AIDS Rep 2014Tobin, N. Curr HIV/AIDS Rep 2014
50SummaryCurrent guidelines provide excellent recommendations for the prevention of perinatal HIV transmissionThere are many obstacles to effectively instituting the appropriate interventions for prevention in all scenarios for HIV + pregnant womenUtilizing the guidelines and initiating appropriate interventions at every opportunity for prevention of perinatal HIV transmission is the only way we can get to “ZERO”