Presentation on theme: "HIV infection in Pregnancy"— Presentation transcript:
1 HIV infection in Pregnancy รองศาสตราจารย์ นายแพทย์ อติวุทธ กมุทมาศสาขาสูติศาสตร์และนรีเวชวิทยาคณะแพทยศาสตร์ มหาวิทยาลัยธรรมศาสตร์
2 Natural history The principal target=T lymphocytes Specific at CD4 surface antigen (receptor for the virus)Monocyte-macrophages may be infectedIncubation period ; days to weeksAcute retroviral syndrome ; fever, night sweats, fatigue, rash, headache, lymphadenophathy, pharyngitis, myalgias, arthralgias, nausea, vomiting, diarrhea ; lasts < 10 days
3 After symptoms abate ; chronic viremia Median time = 10 years --- AIDSAIDS; generalized lymphadenopathy, oral hairy leukoplakia, aphthous ulcer, thrombocytopenia, opportunistic infections (candida, HSV, TB, CMV, HPV, PCP, toxo), Kaposi sarcoma, non-Hodgkin lymphomaDeath
4 Number of People with HIV/AIDS by Region Western Europe500,000Eastern Europe &Central Asia270,000North America890,000East Asia& Pacific560,000North Africa &Middle East210,000Caribbean330,000South andSouth East Asia6.7 millionNorth America: 890,000Caribbean: 330,000Latin America: 1.4 millionWestern Europe: 500,000Eastern Europe and Central Asia: 270,000North Africa and the Middle East: 210,000Sub-Saharan Africa: 22.5 millionEast Asia and the Pacific: 560,000South and South East Asia: 6.7 millionAustralia and New Zealand: 12,000Sub-SaharanAfrica22.5 millionLatinAmerica1.4 millionAustralia and New Zealand12,000Source: UNAIDS/WHO 1998.
5 Virology DNA retrovirus HIV-1 , HIV-2 Transmission - sexually transmitted- blood-contaminated (e.g., blood transfusions, shared needles, contaminated instruments)- maternal to child-vertical 15-40%-breast feeding 30-40%HIV-1 = more common and more virulent
6 Maternal to child transmission (MTCT) 36 wk-labor<14 wk14-36 wkIntrapartum75 %uninfected25 %infected814124% % % %Kourtis and colleagues, 2001
7 Risk factors for vertical transmission 1. Preterm birth (3.7 relative risk for intrapartum transmission ; Kuhn and assoc 1999)2. Prolonged membrane rupture (increase rate from 15 to 25% in ROM > 4 hr ; Landesman and co-workers 1996)3. Placental inflammation, chorioamnionitis, concurrent syphylis (Mwanyumba 2002)C/S reduce vertical transmissionAntibiotics not prove to decrease the risk
8 4. Maternal plasma HIV RNA level ARV decrease the riskMost important factor,HIV RNA viral load > copies/ml : risk > 30 %HIV RNA viral load < 400 copies/ml : risk 1 %
9 5. Stage of disease6. CD4+ T-cell count7. Mode of deliverycesarean section vs vaginal delivery8. Breast feeding (risk 30-40%)
10 Pregnancy on HIV infection HIV infection on pregnancyPregnancy: slightly immunosuppressive: minimal effect on CD4 count: minimal effect on HIV RNA level: does not have significant effect on the clinical or immunological course of HIV infection (Minkoff 2003)Maternal morbidity and mortality: not increasedSlightly increase rate of preterm birthSlightly increase rate of IUGRSlightly increase rate of PROMFetal and neonatal infectionvaries from percent
11 Adverse Pregnancy Outcomes and Relationship to HIV Infection Spontaneous abortionLimited data, but evidence of possible increased riskStillbirthNo association noted in developed countries; evidence of increased risk in developing countriesPerinatal mortalityNo association noted in developed countries, but data limited; evidence of increased risk in developing countriesNewborn mortalityLimited data in developed countries; evidence of increased risk in developing countriesIntra-uterine growth retardationEvidence of possible increased riskThere may be association between HIV and:Spontaneous abortionStillbirthMaternal mortalityNewborn mortalityLow birth weightPreterm deliveryAmnionitisAnderson 2001.
12 Relationship to HIV Infection Adverse Pregnancy Outcomes and Relationship to HIV Infection (continued)Pregnancy OutcomeRelationship to HIV InfectionLow birth weightEvidence of possible increased riskPreterm deliveryEvidence of possible increased risk, especially w/ more advanced diseasePre-eclampsiaNo dataGestational diabetesAmnionitisLimited data; more recent studies do not suggest an increased risk; some earlier studies found increased histologic placental inflammation, particularly in those with preterm deliveriesOligohydramniosMinimal dataFetal malformationNo evidence of increased riskAnderson 2001.
13 Management during pregnancy Therapeutic goals; maximal suppression of viral load and restoration of immunological function; prevention of maternal to child transmissionARV therapy should be offered to all HIV infected pregnant women regardless of CD4 cell count or HIV RNA levelTo treat the mother as well as to reduce the risk of perinatal transmissionHolistic care : antepartum / intrapartum / postpartum: mother / fetus-baby: psycho / bio / social
14 Antepartum care Posttest counseling / psychological support History takingPhysical examinationPer vaginal examinationOral health examinationOphthalmic examinationLab testsTuberculin testChest X-rayPrenatal care in high risk clinicNutrition support / vitamin supplementationUltrasoundPrevention of opportunistic infectionImmunizationAnteretroviral administration
15 Intrapartum care ARV during labor period ; minimum viral load Mode of deliveryLabor augmentation is used when needed to shorten the interval to delivery / but avoid ARMMinimize operative obstetrics : scalp electrode, fetal scalp blood sampling, forceps extraction, vacuum extractionUniversal precaution ; percutaneous exposure of needle=0.3%, mucous membrane exposure=0.09%, atraumatic needle, absorbable suture, non-touch technique, 0.5% sodium hypochloride, room for isolationAdditional vaccine ทำเมื่อ viral suppression is achieved
16 Cesarean section ; decrease vertical transmission one-half compared with vaginal delivery (metaanalysis of 15 prospective cohort studies by the international perinatal HIV group 1999)Combined cesarean section with ARV reduced the risk 87 %ACOG 2000 ; recommended C/S when HIV RNA viral loads > 1000 copies/mlScheduled C/S is recommended at 38 wkIf viral load < 1000 copies/ml ; data insufficient to estimate benefit of C/S (ACOG 2000)
17 Postpartum care 1. ARV Mother: AIDS, HIV infection with CD4<200 ; continue ARV treatmentCD ; controversial for ARVCD4 > 350 ; stop ARV , monitoring CD4Baby: ARV 1 / 6 weeksIf delivery occurs before treatment is given, the newborn can receive prophylaxis for 6 weeks with zidovudine, or in some cases combination antiretroviral treatment2. Contraceptives ; condom + OCPpoints of interest ; TR, injectable, norplant, IUD
18 3. Breast feedingNot recommendedAfrica ; breast feeding with continuation of ARV prophylaxis4. Postpartum clinic and pap smear ; 6 mo / 1 year
19 Guidelines for ARV in pregnancy 1. Classes of ARV drugsBy FDA pregnancy category classificatione-text McGrawHillCunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap III L, Wenstrom KD. Williams Obstetrics. 22nd ed. New York: McGRAW-HILL; 2005.
23 3. MonitoringCD4 count at initiation then CD4 count every 3 monthsHIV RNA levels at 4 weeks after initiation of treatment then HIV RNA levels monthly until undetectable, then every 3 monthsHIV RNA level at GA 36 weeks
27 NVP concentration after SD-NVP Median T1/2 = 61.3 hoursDrug can be detected up to 19 daysLower limit assay quantification 50 ng/ml ; 3-4 weeks postpartumCressey TR. JAIDS 2005; 38:SD NVP covering the tail ; ZDV/3TC 7 days : reduce resistance from 60 % to %TOPH Trial, SA
29 HAART Depend on immune status of mother -low CD4 <200 ; start for maternal health-high CD4 ; consider-pro ; low TR (PACTG316, TR 1.5%)-con ; high risk of NVP toxicity, increase risk of GDM with PI, risk of preterm delivery (controversial)Which HAART?-NNRTI based HAART-PI based HAART
30 Toxicities concerned NVP -rash ; women>men (3.7 x) -more common with high CD4 > 250 (10X increase in women)Hepatotoxicity-symptomatic hepatotoxicity ; CD4 <250 : %, CD4 > 250: %-fetal hepatic events ; CD : 0.42%, CD4 >400 : 1.1%)-TRC cohort ; low : high CD4 2.9% versus 7.7%
37 AZT regimen Prevalence of HIV infection pregnancy in TUH = 1-2 percent AZT alone = infection rate 3.9 percentAZT regimen from other studies ; infection rate 5-8 percent, ACTG 076 protocol = 8%Cesarean section = beneficialMPH ; still using AZT regimen
38 Regimens ; Pediatrics AIDS clinical trials group, USA Antepartum: 100 mg 5times/day, initiating at wk,continue throughout pregnancy (or 200 mg 3times/day, 300 mg twice a day)Intrapartum: IV Zidovudine in a 1-hr initial dose of 2 mg/kg, followed by a continuous infusion of 1 mg/kg/hr until deliveryNeonates: begin at 8-12 hr after birth, and give syrup at 2 mg/kg every 6 hr for 6 weeks
39 Intrapartum; AZT 300 mg every 3 hr and single dose NVP 200 mg orally Regimen MPHAntepartum; 300 mg twice a day, initiating at (28) wk,continue throughout pregnancy (regardless of CD4 count)Intrapartum; AZT 300 mg every 3 hr and single dose NVP 200 mg orallyPostpartum; AZT 300 mg+3TC 150 mg twice a day for 2 weeksNeonates; NVP 2 mg/kg single dose and AZT 2 mg/kg every 6 hr for 6 weeksDisadvantages (compare to HARRT) :Higher transmission rateHigh incidence of NVP resistance
42 Regimen : TUH1. CD4 ≤ 200 / GA 14 weeksAntepartum; AZT(300)/3TC(150) q 12 hr + NVP(200) OD for 2 wk then AZT(300)/3TC(150) +NVP(200) q 12 hrIntrapartum; AZT 300 mg q 3 hr and AZT(300)/3TC(150) +NVP(200) q 12 hrPostpartum; AZT(300)/3TC(150) +NVP(200) q 12 hrNeonates; AZT 2 mg/kg q 6 hrx6 wk
43 2. CD4 > 200 / GA 28 weeksAntepartum; AZT(300)/3TC(150) q 12 hr + NVP(200) OD for 2 wk then AZT(300)/3TC(150) +NVP(200) q 12 hrIntrapartum; AZT 300 mg q 3 hr and AZT(300)/3TC(150) +NVP(200) q 12 hrPostpartum; AZT(300)/3TC(150) q 12 hr x 14 days, stop NVPNeonates; AZT 2 mg/kg q 6 hrx6 wk
44 Alternative regimens; AZT/3TC/Nelfinavir(NLF) (250 mg 5 tabs q 12 hr, no need for test dose, no covering tail)AZT/3TC/Efavirenz (GA>24wk)GPOvir(3TC/d4T/NVP)(follow the protocol AZT/3TC/NVP and test doses NVP for 2 wk)In case C/SStart AZT with 30 cc of water since NPO then NPO except medicine with water until delivery and postop care period hrFor no ANC patientsIntrapartum; AntiHIV stat, NVP 200 mg single dose (immediately) and AZT 300 mg q 3 hr regardless of CD4 countPostpartum;AZT300/3TC150 q 12 hrx14wkNeonates; NVP 2 mg/kg single dose + AZT 2 mg/kg q 6 hr x 6 wk (start immediately)
45 Thank you for your attention until the end of the session