The HIV Exposed Infant Morning Report October 2005 Background In the US, more than 90% of reported cases of AIDS in children are due to perinatal transmission The other 10% are from blood transfusions, sexual abuse and unknown sources All pregnant women should be offered counseling and testing for HIV infection during pregnancy Prevention of Transmission In 1994, the US Public Health Service published guidelines for use of zidovudine in the HIV infected woman during pregnancy to decrease the risk of perinatal transmission of HIV In 1995, the AAP and US Public Health Service recommended documented, routine HIV education and testing with consent for all pregnant women in US Incorporation of these guidelines has resulted in a dramatic decrease in the rate of perinatal HIV transmission and a 75% decrease in reported cases of pediatric AIDS CDC estimates that the rate of new cases of perinatal HIV infection has decreased from 1500 to 300-400 per year Effective August 2003 Enacted to prevent mother-to-newborn transmission of HIV Health care professionals are required to offer HIV counseling and strongly encourage voluntary testing to all pregnant women and their infants Counseling and testing should be offered prenatally, during delivery and post-partum All testing must be obtained by consent Mother must sign written consent before HIV test If mother’s status is unknown, consent for testing infant is presumed and should be done unless mother refuses in writing HIV Counseling All HIV counseling of pregnant women should be done in accordance with the AIDS Confidentiality Act and should include: – Benefits of HIV testing for pregnant women, including opportunity for prevention of transmission – Benefit of testing infant, including interventions to prevent transmission – Side effects of interventions – The confidentiality provisions that relate to HIV and AIDS – The voluntary nature of testing, including the opportunity to refuse testing of infant in writing Epidemiology In 1999, 41% of young adults 13-24 years old with AIDS were females In US, approximately 25% of HIV transmission is estimated to occur among people younger than 21 years of age Sexually active youth everywhere are at risk unless barrier protection is used Heterosexual contact surpassed IV drug use as the predominant mode of HIV transmission for women with AIDS in 1992 Epidemiology The transmission rate of HIV in infected, untreated pregnancies is approximately 25% The transmission rate with antenatal, intrapartum and infant prophylactic antiretroviral therapies is less than 2% Epidemiology Studies on timing of transmission suggest that in a nonbreastfeeding population, 25-40% of transmission occurs in utero Absolute risk for in utero transmission is 5%, intrapartum transmission is 13-18% Maternal viral load is critical determinant of perinatal HIV transmission Other factors: CD4+ count, advanced maternal illness, intrapartum events resulting in increased exposure to maternal blood, placental inflammation, premature delivery, prolonged labor, prolonged ROM Epidemiology Women who seroconvert during pregnancy may be at higher risk for in utero transmission Reduction of maternal HIV viral load to a nondetectable level is the key to preventing vertical transmission C/S may be helpful in preventing peripartum transmission Postpartum transmission occurs through breastfeeding – Worldwide, 1/3 to 1/2 of transmission – In US, it is possible to offer safe alternative HIV Tests Expedited enzyme immunoassays – Uses first step of standard laboratory HIV-1 antibody testing – Positive and negative results within 24hr – A positive result must be confirmed by Western blot analysis Rapid test kit – Tests a single specimen for HIV-1 antibodies – Results available within minutes to 2 hrs – OraQuick Rapid and Single Use Diagnostic System (SUDS) HIV-1 tests are licensed in US – Rapid should be confirmed by standard testing If positive test results, a confirmatory supplemental test is required HIV Tests Antibody-based assays (EIA, Western Blot) cannot be used in infancy due to transplacental transfer of antibody HIV nucleic acid detection by PCR assay of DNA from peripheral blood is the preferred test for diagnosis of infants – Available within 24hours – Approx 30% of infants with infection will have a positive test by 48 hours – Single assay has sensitivity of 95%, specificity of 97% in infants 1 to 36 months of age Virus isolation by culture is expensive and takes up to 28 days for results p24 antigen is less sensitive HIV RNA PCR assay Can diagnose HIV infection only if result is positive This test can be negative in HIVinfected individuals Licensed by FDA only in quantitative format Currently used for quantifying the amount of virus present as a predictor of disease progression HIV Testing of the Infant If mothers status is unknown: Test the infant with maternal consent (right of refusal) HIV DNA PCR should be sent during the first 48 hours of life Some states mandate testing of all infants whose maternal status is unknown HIV Diagnosis HIV DNA PCR for diagnosis at < 48 hours of life 14 days 1 to 2 months 2 to 4 months If positive test, repeat test on second blood sample Infection = 2 separate samples positive on 2 separate dates HIV Diagnosis Infection can be excluded if: 2 or more negative HIV DNA PCR tests at age > 1 month PLUS a negative test at age >4 months OR 2 or more samples negative for HIV antibody at >6 months (interval of one month) Laboratory Findings In a perinatally infected infant, notable findings may include – High viral load (HIV RNA PCR) that does not decrease rapidly in first year of life – Increasing loss of cell immunity – Lymphocyte count may be normal but eventual decrease in CD4+ results (age related norms) – T-suppressor CD8+ cells increase initially and are not depleted until late in course of infection – Elevated IgG and IgA levels are manifestations of humoral immune dysfunction Antiretroviral Agents Three categories of drugs each with a site of action against HIV replication Reverse transcriptase inhibitors target an enzyme that converts HIV RNA to DNA for transcription by the host cell genome – Nucleoside analogue agents (Zidovudine) – Nonnucleoside analogue agents (Nevirapine) Blocking the protease enzyme is a second site of action – Protease inhibitors (indinavir) Antiretroviral Prophylaxis If Maternal HIV known during Pregnancy Antepartum: Oral Zidovudine (ZDV) beginning at 14 to 34 weeks gestation continuing through pregnancy Intrapartum: IV ZDV infusion until delivery Postpartum: Oral ZDV syrup (2mg/kg/dose Q 6 hrs) to newborn infant within 6-12h of birth for the first 6 weeks of life *this regimen decreased transmission by 2/3 in clinical trials Antiretroviral Prophylaxis Maternal HIV diagnosed during Labor If maternal HIV status is determined only at the time of labor and delivery, any of the following regimens have been shown to be effective for prevention of transmission: – Maternal oral dose of nevirapine (NVP) at onset of labor followed by a single oral dose of NVP for infant at 48-72 hr – Intrapartum oral ZDV and lamivudine (3TC) followed by 1 week of oral ZDV and 3TC for infant – Intrapartum intravenous ZDV followed by 6 weeks of ZDV for infant – Combination of ZDV and NVP regimen Postnatal Antiretroviral Prophylaxis When birth: HIV status known only after – No prenatal or intrapartum therapy received – Data suggest that 6 weeks of ZDV prophylaxis given to infant may provide some protection if given within first 24 hours – Some may add additional antiretroviral drug, as in post exposure prophylaxis Cesarean Section Rate of transmission decreased by 50% (in absence of ZDV) when delivery was by elective C/S before ROM and onset of labor With antiretroviral therapy and C/S, rate decreased to 2% Vaginal delivery and antiretroviral therapy had rates of 7% If HIV RNA level is undetectable, rates of perinatal transmission is low even with vaginal delivery – C/S may not outweigh risk of operation ACOG recommends counseling women with viral loads > 1000/ml about the benefit of C/S delivery Management of HIV Infected Infant Infection = 2 separate HIV DNA PCR assays positive on 2 separate dates Consult HIV specialist Initiate treatment in all HIV-infected infants < 12 months who have clinical or immunologic abnormalities Consider treatment in those < 12 months that are asymptomatic Recommendation based on rapid disease progression in infants HIV Antibody Testing In HIV exposed infants, serologic testing after 12 months of age is used to confirm that maternal ab transferred have disappeared If antibodies negative and previous HIV DNA PCR tests were negative, child is not infected If HIV antibody is + at 12 months, repeat test at 18 months Positive HIV antibodies at > 18 months indicates infection PCP Prophylaxis PCP is the most serious opportunistic infection in HIV infected children It is recommended that PCP prophylaxis be started at 4-6 weeks of age (near completion of ZDV prophylaxis) Discontinue prophylaxis when HIV infection can be reasonably excluded Immunizations All routine immunizations should be given to HIV exposed infants For HIV infected infants, standard immunizations are recommended including: – Influenza if CD4+ counts are not low – Varicella if CD4+ counts are normal References Pickering, L and the American Academy of Pediatric. Red Book 2003 Report of the Committee on Infectious Diseases pp.360-380. Burchett, S. HIV Infection in Infants, Children, and Adolescents. Pediatrics in Review 2003; 24 (6) King, S and Committee on Pediatric AIDS and Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Evaluation and Treatment of the Human Immunodeficiency Virus-1 – Exposed Infant. Pediatrics 2004; 114; 497-505. Mofenson, LM and the Committee on Pediatric AIDS. Technical Report: Perinatal Human Immunodeficiency Virus Testin and Prevention of Transmission. Pediatrics 2000; 106; 88. The Illinois Prenatal HIV Prevention Law. Guidelines for Delivery of Care.