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OBJECTIVES EPIDIMIOLOGY Concentrate on Obstetrics and Gynecology The virus CLINICAL FEATURES SCREENING + DIAGNOSTIC TESTS HIV in Obstetrics Population To screen or Not to screen. 1 Cont. OBJECTIVES PRE- + POST TEST COUNSELLING PERINATAL TRANSMISSION VIRAL LOAD + PERINATAL TRANSMISSION 2 Cont. OBJECTIVES MANAGEMENT OF OBSTETRICS PATIENT WITH AIDS Reduction of perinatal transmission Vaccination Drug therapy for AIDS related infection Delivering AID patient 3 CASES REPORTED 1999 TOTAL : 5.6 MILLION MALES : 2.7 MILLION FEMALES : 2.3 MILLION CHILDREN : 570 HUNDRED THOUSAND 90% OF THESE ARE PERINATAL TRANSMISSION 4 NUMBER OF DEATHS 1999 TOTAL : 2.6 MILLION MALES : 1 MILLION FEMALES : 1.1 MILLION CHILDREN : 470 HUNDRED THOUSAND 5 NUMBER OF AIDS 1999 TOTAL : 33.6 MILLION MALES : 17.6 MILLION FEMALES : 14.8 MILLION CHILDREN : 1.2 MILLION 6 NUMBER OF AIDS 2000 TOTAL : 34.7 MILLION MALES : 18.3 MILLION FEMALES : 16.4 MILLION 7 NUMBER OF DEATHS UNTIL 1999 TOTAL : 16.3 MILLION MALES : FEMALES : CHILDREN : 6.5 MILLION 6.2 MILLION 3.6 MILLION 8 ETIOLOGY RNA TYPE I TYPE II : RETROVUS : COMMENTIST : MORE COMMON IN WEST AFRICA 9 1981 1983 1984 - Internal case Virus disease Antibodies tests developed (Cumulative cases) 10 PATHOLOGY TARGET CELLS CD4 Helper lymphocytes (Primary Target) Macrophages CNS Placenta SUPRESS IMMUNITY INCREASE SUSCEPTIBILITY TO OPPORTUNISTIC INFECTIONS AND NEOPLASMS 11 I am an Obstetrician not an Internist, why should I be HIV oriented? 12 14% of HIV infected patients are women. HIV is the third leading cause of women age 25-44 years ( in USA) Prevalence of HIV infected pregnant women is 16:1000 90% of HIV infection in children worldwide is related to perinatal transmission of the virus. 85% of AIDS cases in women between ages 15-44 years. 13 CLINICAL FEATURES At the time of exposure asymptomatic acute mild syndrome similar to mononucleosis Latest Period (Window Phase) (Seroconvertion) Viral isolation - Antigen (PCR) 14 Immune dysfunction phase wide range of clinical condition P.U.O. Weight loss Lymphadenopathy CNS dysfunction Abnormal Pap tests Recurrent C.I.N. Recurrent oral and vaginal candidiasis 15 CLASSIFICATION OF THE DISEASE 16 SEROCONVERTION ILLNESS 17 SCREENING TEST To detect antibodies to the virus rather that the virus itself ELISA – 3 weeks-3 months to appear 18 CONFIRMATORY TEST WESTERN BLOT ASSAY Sensitivity and specificity are more than 99% Repeating the test will eliminate the false positive result. 19 TO SCREEN OR NOT TO SCREEN? The best defense is a strong offense. The American Academy of Paediatrics and the ACOG issued a Joint Statement on HIV Screening in Pregnancy (1995). A pregnant women should receive HIV counseling as part of their routine ANC. A pregnant women should have HIV testing with their consent. 20 PRE-TEST COUNSELING Risks of transmission (including Mode) Risks of perinatal transmission Potential social and psychological implication of Positive test. The availability of Agents that may reduce the risk of neonatal infection. Clarify the difference between HIV infection and disease. 21 POST-TEST COUNSELING NEGATIVE Test in High Risk Patient should be informed about false Negative Results related to the latest period. 22 PATIENT WITH POSITIVE TEST Description of early clinical manifestation of HIV infection. Current understanding of the prognosis. Risk of Perinatal transmission. Prohibition from blood donation. Not to share instrument that may be exposed to blood, like toothbrush. 23 Cont. PATIENT WITH POSITIVE TEST Testing for the partner. Psychological and emotional support Discuss the strategies available to maintain better quality of life. Emphasis the importance of follow up. 24 PERINATAL TRANSMISSION In the absence of treatment, the risk of Perinatal transmission is 13-40%. Time of transmission - not certain yet. ? 50% during labor and delivery. 25 FACTORS ASSOCIATED WITH INCREASE RISK OF PERINATAL TRANSMISSION. Low CD4 count. Scalp electrode – scalp sampling. Prolonged rupture of membrane. Viral blood 26 FOLLOW UP CD4 Count (Monthly) Viral blood were viral RNA Quantitative measures are available. 27 REDUCTION OF PERINATAL TRANSMISSION Multicenter trial - N. Eng. J 1994 Showed reduction of rate of Perinatal Transmission from 25% - 8% using ZDV between 14-34 weeks. No increasing in the congenital anomalies. No major side effect. 28 DELIVERY No evidence to support C/S to reduce the risk of infection. A R M , scalp electrode, fetal scalp sampling should be avoided. 29 POSTPARTUM • AVOID BREAST FEEDING Risk by 10-20 % 30 PROVISIONAL PUBLIC HEALTH SERVICE RECOMMENDATION FOR CHEMO PROPHYLAXIS AFTER HIV EXPOSURE (1996) PERCUTANEOUS EXPOSURE HIGH RISK Large volume of blood (deep injury with large diameter load exposed to HIV positive patient RECOMMEND AZT Acute viral illness – AIDS, High Viral Load RECOMMEND AZT 31 NO HIGH RISK Exposure to liquids and secretion that are potentially infection. OFFER AZT 32 MUCOSAL EXPOSURE Blood Offer Fluid contaminated – not offer SKIN EXPOSURE Blood offer Other fluid - not offer 33 PRECAUTIONS: Double gloving Eye coverage at delivery Avoid mouth suction in resuscitating the neonates Careful handling of needles + sharps Use closed vacuum collection system for blood with ___________. 34 WHEN THE HIV TEST IS POSITIVE Check the following: General Health Status Past Medical History - General well being - Constitutional symptoms - Nutritional assessment - Gynecologic/obstetrical history: menstrual irregularity, previous abnormal Pap smears - Receipt of blood transfusions or other blood products 35 Drug History - Medication: prescription and non-prescription - Complementary therapies - Recreational use: smoking, alcohol, injection drug use including steroids, and street drugs 36 SEXUAL HISTORY - STDs Sexual activities Previous sexual partners Current sexual partners Current sexual practices Partners at risk Method of contraception 37 Risks of Infectious Complications Immunizations Travel history Previous countries of residence Country of origin Occupational history Personal and family history of TB Previous PPD results Personal and family history of hepatitis B & C 38 Psychosocial History Education Social supports Financial and employment background 39 REVIEW OF SYSTEMS - GENERAL Constitutional symptoms of : Fatigue Fever Sweats and night sweats Loss of appetite and weight Skin/Mucous Membranes Lesions Rashes Bruising Ulcers Pain/tenderness 40 Respiratory Upper: nasal and sinus congestion and pain Lower: cough, sputum, shortness of breath, chest pain. Gastrointestinal - Taste - Nausea - Vomiting - Diarrhea - Hepatitis - Dysphagia Vomiting Abdominal & rectal pain Jaundice 41 Genitourinary Dysuria Discharges Pelvic pain Neurologic System Central: cognitive, memory, personality, seizures, weakness/pain/tingling/balance, visual changes Peripheral: weakness/pain/tingling in extremities 42 Psychiatric Mood Libido Cognitive Concentration Thought content Sleep 43 BASELINE LABORATORY INVESTIGATION The Minimum Baseline tests are: Chest X-ray CBC and differential, smear, platelets B12 and Folic acid BUN and Creatinine, liver function, electrolytes Pap smear for women Appropriate swabs for STDs, syphilis serology TB skin test Hepatitis B and C screening Toxoplasmosis titre Absolute CD4, % CD4 of total lymphocytes CMV IgG Serology 44 BASELINE PHYSICAL EXAMINATION Check the following: Weight, Temperature, and Vital Signs Head and Neck - Oral lesions - Sinus tenderness - Nasal congestion Lymph nodes - Cervical - Supraclavicular - Axillary - Inguinal 45 Cont. Baseline Physical Examination Chest and Cardiovascular Abdominal and Rectal - Air entry Adventitial sounds Murmurs Tachycardia Hepatosplenomegaly Abdominal tenderness Rectal lesions 46 Cont. Baseline Physical Examination Genito-urinary - Discharge - Genital lesions Pelvic - Vaginal discharge - Cervical lesions - Pelvic and adnexal mass and tenderness 47 Cont. Baseline Physical Examination Neurologic Mental Status Skin - Fundoscopic and visual field changes Focal motor/sensory signs Mood/affect Cognitive/perceptive Memory/judgment/insight Rashes Ulcers Lesions, including Kaposi’s sarcoma (KS) 48 TRANSMISSION OF THE VIRUS Sexual intercourse anal and vaginal Contaminated needles Intravenous drug users needlestick injuries injections 49 Mother child in utero at birth breast milk Organ/tissue donation Semen Kidneys Skin, bone marrow, corneas, heart valves, tendons, etc. 50 HIV Transmission: Global Summary Type of exposure % of Global Total a) Blood Transfusion 3–5 b) Perinatal 5 – 10 c) Sexual intercourse 70 – 80 (Vaginal) (60 – 70) ( Anal) ( 5 – 10) d) Injecting drug use (sharing needles, etc) 5 – 10 e) Health care (needlestick injury, etc) <0-0151 Cumulative AIDS cases reported to the World Health Organization, June 1996 The Americas Europe Africa Oceania Asia - 690,042 167,578 499,037 7,285 ___29,707___ TOTAL - 1,393,649 52 For women with CD4 counts above 500 cells/mm3: Cervicovaginal cytology (Pap smear) six months x 2, if adequate and negative, then annually If Pap smear is positive for the presence of HPV, with koilocytes or condyloma: Three-monthly Pap smear Six-monthly colposcopic acetic acid examination 53 For women with CD4 counts from 200 to 500 cells/mm3: Six-monthly Pap smear Baseline colsposcopic examination using acetic acid visualization, to be repeated annually if Pap smear is negative, or sixmonthly if the presence of HPV is detected. 54 For women with CD4 counts under 200 cells/mm3: Three-monthly Pap smear Colposcopic examination using acetic acid visualization, to be repeated six-monthly 55 First Aid and Inoculation Injuries FIRST AID Body fluids on skin, in eyes, or in mouth Wash away immediately Penetrating wounds Encourage bleeding Wash with soap and water Report to supervisor and medical officer 56 ZIDOVUDINE THERAPY ANTEPARTUM Oral administration of 100mg of Zidovudine (ZDV) five times daily, initiated as soon as possible beyond 14 weeks of gestation and continued throughout the pregnancy. LABOR AND DELIVERY During labor, intravenous administration of ZDV in a 1-hour loading dose of 2mg/kg of body weight, followed by a continuous infusion of 1 mg/kg of body weight per hour until delivery. 57 Cont. ZIDOVUDINE THERAPY NEONATAL Oral administration of ZDV to the newborn (ZDV syrup at 2mg/kg of body weight per dose every 6 hours) for the first 6 weeks of life, beginning 8-12 hours after birth. 58 RISKS TO HEALTH WORKER Needle stick. Risk is .32% or 32:1000 Mucous membranes – Percutaneous exposure to infected blood. 0.03% or 3:1000 No evidence that the virus is spread by mosquitoes, lice, bed bugs, swimming pools, sharing cups or eating and cooking utensils, toilets. 59 FIRST AID MANAGEMENT TO EXPOSURE TESTING ___________ Repeat in 6weeks – 3 months - - - 6 months Test for other blood born infection Hepatitis B & C – risk may _______ 30%. PROPHYLACTIC USE OF AZT 60 RISK OF BLOOD TRANSFUSION HEPATITIS HIV - 1: 100,000 1: 500,000 61 HIV IN GYNECOLOGICAL PATIENT STD Recurrent candida infection refractory to conventional treatment. Recurrent cervical dysplasia - cervical ca. Recommend follow up in HIV positive. 62 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 Recommendation: Initiate maternal ZDV regardless of plasma HIV RNA or CD4 counts. 63 Changing HIV Therapy During Pregnancy Poor CD4 response Drugs with potential teratogenicity Poor viral load response Poor adherence to regimen Evidence of viral resistance 64 Follow-Up Assessment of Pregnant Woman with HIV 4 weeks after initiation of treatment, then every 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 65 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 hours. 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 IV66ZDV and six week ZDV for the newborn. CLINICAL SCENARIO 2 Women currently on antiretroviral therapy: Discuss benefits and potential risks of her current regiment 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. 67 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 1000 regardless of clinical or immunologic status • 3-part ZDV regimen to reduce perinatal transmission for all HIVinfected 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). 68 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 would RNA <30,000 (bDNA) or <55,000 delay therapy & 69 (RT-PCR) observe 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 70 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 71 Follow-Up of Uninfected Infants in 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. 72 Maternal Viral Load and Risk of Transmission (Women & Infants Transmission Study (WITS) ) HIV – 1 RNA <1000 1000 – 10,000 10,001 – 50,000 50,001 - 100,000 >100,000 Transmission % 0 16.6 21.3 30.9 40.6 N 0/57 32/193 39/183 17/54 26/64 73 Factors Influencing Perinatal Transmission Maternal Factors HIV-1 RNA levels (viral load) Low CD4 lymphocyte count Other infections, Hepatitis C, CMV, bacterial vaginosis Maternal infection drug use Lack of ZDV during pregnancy Obstetrical Factors Length of ruptured membranes/chorioamnionitis Vaginal delivery Invasive procedures Infant Factors Prematurity 74 Timing of Perinatal HIV Transmission Cases documented 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 75 National Recommendation for HIV Testing of Pregnant Women Universal testing with patient notification as a routine component of prenatal care American Academic of Pediatrics and the American College of Obstetricians and Gynecologists Joint Statement 1999 76 Impact of PHS Guidelines for Reducing Perinatal HIV Transmission 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% 77 Scope of the Epidemic Among Women and Children 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. 78 RECOMMENDATIONS (SOGC Infectious Disease Committee) Elective cesarean section (38 weeks gestation) has a valuable role for pregnant women with HIV and should be offered in these specific situations: 1. Women who have not received antiretroviral therapy regardless of the antepartum viral load determination. 2. Women receiving antiretroviral monotherapy regardless of the viral load. 3. Patients with detectable viral load regardless of the received therapy. 79 PEOPLE NEWLY INFECTED WITH HIV IN 2001 TOTAL 5 MILLION ADULTS WOMEN CHILDREN <15 YEARS 4.2 MILLION 2 MILLION 800,000 80 NUMBER OF PEOPLE LIVING WITH HIV/AIDS As of End of 2001 TOTAL 40 MILLION ADULTS WOMEN CHILDREN <15 YEARS 37.1 MILLION 18.5 MILLION 3 MILLION 81 AIDS DEATH IN 2001 TOTAL ADULTS WOMEN CHILDREN <15 YEARS 3 MILLION 2.4 MILLION 1.1 MILLION 580,000 82 TOTAL NUMBER OF CHILDREN ORPHANED BY AIDS, AND LIVING, END 2001 14 MILLION 83 PROPHYLACTIC DRUG THERAPY FOR AID RELATED INFECTIONS When CD4 count less that 200/mm2 P carinii pneumonia prophylaxis should be started Trimethropin-Sulfamehoxazole (Bactrim-Septra) 160mg/day Other – Diaphenylsuphane (Dopsane) 100mg daily Pentamide 60mg every 2 weeks AZT prophylaxis should be started 84 RECURRENT CANDIDA Oral Ketoconazole 400mg Fluconazole 100mg or ANTI TB INH or Rifamycin 85 IMMUNIZATION Susceptible patients should received: Hepatitis B Pneumococcal Influenza vaccine 86