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HIV infection in Pregnancy. Natural history The principal target=T lymphocytes The principal target=T lymphocytes Specific at CD4 surface antigen (receptor.

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Presentation on theme: "HIV infection in Pregnancy. Natural history The principal target=T lymphocytes The principal target=T lymphocytes Specific at CD4 surface antigen (receptor."— Presentation transcript:

1 HIV infection in Pregnancy

2 Natural history The principal target=T lymphocytes The principal target=T lymphocytes Specific at CD4 surface antigen (receptor for the virus) Specific at CD4 surface antigen (receptor for the virus) Monocyte-macrophages may be infected Monocyte-macrophages may be infected Incubation period ; days to weeks Incubation period ; days to weeks Acute retroviral syndrome ; fever, night sweats, fatigue, rash, headache, lymphadenophathy, pharyngitis, myalgias, arthralgias, nausea, vomiting, diarrhea ; lasts < 10 days Acute retroviral syndrome ; fever, night sweats, fatigue, rash, headache, lymphadenophathy, pharyngitis, myalgias, arthralgias, nausea, vomiting, diarrhea ; lasts < 10 days

3 After symptoms abate ; chronic viremia After symptoms abate ; chronic viremia Median time = 10 years --- AIDS Median time = 10 years --- AIDS AIDS; generalized lymphadenopathy, oral hairy leukoplakia, aphthous ulcer, thrombocytopenia, opportunistic infections (candida, HSV, TB, CMV, HPV, PCP, toxo), Kaposi sarcoma, non-Hodgkin lymphoma AIDS; generalized lymphadenopathy, oral hairy leukoplakia, aphthous ulcer, thrombocytopenia, opportunistic infections (candida, HSV, TB, CMV, HPV, PCP, toxo), Kaposi sarcoma, non-Hodgkin lymphoma Death Death

4 4 Number of People with HIV/AIDS by Region North America 890,000 Caribbean 330,000 Latin America 1.4 million Western Europe 500,000 Sub-Saharan Africa 22.5 million Eastern Europe & Central Asia 270,000 East Asia & Pacific 560,000 South and South East Asia 6.7 million Australia and New Zealand 12,000 North Africa & Middle East 210,000 Source: UNAIDS/WHO 1998.

5 Virology DNA retrovirus DNA retrovirus HIV-1, HIV-2 HIV-1, HIV-2 Transmission - sexually transmitted Transmission - sexually transmitted - blood-contaminated (e.g., blood transfusions, shared needles, contaminated instruments) - blood-contaminated (e.g., blood transfusions, shared needles, contaminated instruments) - maternal to child - maternal to child -vertical 15-40% -breast feeding 30-40%

6 Maternal to child transmission (MTCT) <14 wk14-36 wk 36 wk- labor Intrapartum % uninfected 25 % infected 4% 16% 50% 30% 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)

8 4. Maternal plasma HIV RNA level Most important factor, HIV RNA viral load > copies/ml : risk > 30 % HIV RNA viral load < 400 copies/ml : risk 1 %

9 5. Stage of disease 6. CD4+ T-cell count 7. Mode of delivery cesarean section vs vaginal delivery cesarean section vs vaginal delivery 8. Breast feeding (risk 30-40%)

10 Pregnancy on HIV infection Pregnancy Pregnancy : slightly immunosuppressive : minimal effect on CD4 count : minimal effect on CD4 count : minimal effect on HIV RNA level : minimal effect on HIV RNA level : does not have significant effect on the clinical or immunological course of HIV infection (Minkoff 2003) : does not have significant effect on the clinical or immunological course of HIV infection (Minkoff 2003) Maternal morbidity and mortality Maternal morbidity and mortality : not increased : not increased HIV infection on pregnancy Slightly increase rate of preterm birth Slightly increase rate of IUGR Slightly increase rate of PROM Fetal and neonatal infection varies from percent

11 Adverse Pregnancy Outcomes and Relationship to HIV Infection Pregnancy Outcome Relationship to HIV Infection Spontaneous abortion Limited data, but evidence of possible increased risk Stillbirth No association noted in developed countries; evidence of increased risk in developing countries Perinatal mortality No association noted in developed countries, but data limited; evidence of increased risk in developing countries Newborn mortality Limited data in developed countries; evidence of increased risk in developing countries Intra-uterine growth retardation Evidence of possible increased risk Anderson 2001.

12 Adverse Pregnancy Outcomes and Relationship to HIV Infection (continued) Pregnancy Outcome Relationship to HIV Infection Low birth weight Evidence of possible increased risk Preterm delivery Evidence of possible increased risk, especially w/ more advanced disease Pre-eclampsia No data Gestational diabetes No data Amnionitis Limited data; more recent studies do not suggest an increased risk; some earlier studies found increased histologic placental inflammation, particularly in those with preterm deliveries Oligohydramnios Minimal data Fetal malformation No evidence of increased risk Anderson 2001.

13 Management during pregnancy Therapeutic goals Therapeutic goals ; maximal suppression of viral load and restoration of immunological function ; prevention of maternal to child transmission ARV therapy should be offered to all HIV infected pregnant women regardless of CD4 cell count or HIV RNA level ARV therapy should be offered to all HIV infected pregnant women regardless of CD4 cell count or HIV RNA level To treat the mother as well as to reduce the risk of perinatal transmission To treat the mother as well as to reduce the risk of perinatal transmission Holistic care : antepartum / intrapartum / postpartum Holistic care : antepartum / intrapartum / postpartum : mother / fetus-baby : mother / fetus-baby : psycho / bio / social : psycho / bio / social

14 Antepartum care 1. Posttest counseling / psychological support 2. History taking 3. Physical examination 4. Per vaginal examination 5. Oral health examination 6. Ophthalmic examination 7. Lab tests 8. Tuberculin test 9. Chest X-ray 10. Prenatal care in high risk clinic 11. Nutrition support / vitamin supplementation 12. Ultrasound 13. Prevention of opportunistic infection 14. Immunization 15. Anteretroviral administration

15 Intrapartum care 1. ARV during labor period ; minimum viral load 2. Mode of delivery 3. Labor augmentation is used when needed to shorten the interval to delivery / but avoid ARM 4. Minimize operative obstetrics : scalp electrode, fetal scalp blood sampling, forceps extraction, vacuum extraction 5. Universal 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 isolation

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) 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 % Combined cesarean section with ARV reduced the risk 87 % ACOG 2000 ; recommended C/S when HIV RNA viral loads > 1000 copies/ml ACOG 2000 ; recommended C/S when HIV RNA viral loads > 1000 copies/ml Scheduled C/S is recommended at 38 wk Scheduled C/S is recommended at 38 wk If viral load < 1000 copies/ml ; data insufficient to estimate benefit of C/S (ACOG 2000) If 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 treatment AIDS, HIV infection with CD4<200 ; continue ARV treatment CD ; controversial for ARV CD ; controversial for ARV CD4 > 350 ; stop ARV, monitoring CD4 CD4 > 350 ; stop ARV, monitoring CD4 Baby: ARV 1 / 6 weeks If delivery occurs before treatment is given, the newborn can receive prophylaxis for 6 weeks with zidovudine, or in some cases combination antiretroviral treatment If delivery occurs before treatment is given, the newborn can receive prophylaxis for 6 weeks with zidovudine, or in some cases combination antiretroviral treatment 2. Contraceptives ; condom + OCP points of interest ; TR, injectable, norplant, IUD points of interest ; TR, injectable, norplant, IUD

18 3. Breast feeding Not recommended Not recommended Africa ; breast feeding with continuation of ARV prophylaxis Africa ; breast feeding with continuation of ARV prophylaxis 4. Postpartum clinic and pap smear ; 6 mo / 1 year

19 1. Classes of ARV drugs By FDA pregnancy category classification e-text McGrawHill Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap III L, Wenstrom KD. Williams Obstetrics. 22nd ed. New York: McGRAW-HILL; Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap III L, Wenstrom KD. Williams Obstetrics. 22nd ed. New York: McGRAW-HILL; Guidelines for ARV in pregnancy

20 DrugCategory Nucleoside reverse transcriptase inhibitors Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zalcitabine Zidovudine Non-nucleoside reverse transcriptase inhibitors Delavirdine Efavirenz Nevirapine Protease inhibitors Amprenavir Atazanavir Fosaprenavir Indinavir Lopinavir/ritonavir Nelfinavir Ritonavir Saquinavir Fusion inhibitors Enfuvirtide CBBCCBCCCCCCBCCCBBBBCBBCCBCCCCCCBCCCBBBB

21 NRTI/ NNRTI FI PI

22 2. Regimens NNRTI-based NNRTI-based PI-based PI-based Triple NRTI-based Triple NRTI-based FI-based FI-based

23 3. Monitoring CD4 count at initiation then CD4 count every 3 months CD4 count at initiation then CD4 count every 3 months HIV RNA levels at 4 weeks after initiation of treatment then HIV RNA levels monthly until undetectable, then every 3 months HIV RNA levels at 4 weeks after initiation of treatment then HIV RNA levels monthly until undetectable, then every 3 months HIV RNA level at GA 36 weeks HIV RNA level at GA 36 weeks

24 4. Heavy, Light, or Medium HeavyMediumLight Short course AZT NVP-single dose Short course AZT+SD NVP AZT+3TC AZT+3TC+NVP AZT+3TC+PI

25 Short course ZDV / SD NVP HIVNET012 ; Guay, Lancet 1999;354: PHPT-2; Lallemant, NEJM 2004; 351: TR 8% (ACTG076) MASHI; Shpiro, AIDS 2006; 20: Short course AZT ; TR 8% (ACTG076) Short course ZDV NVP-NVP P-P NVP-P NVP-NVP P-NVP

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27 NVP concentration after SD-NVP Median T1/2 = 61.3 hours Drug can be detected up to 19 days Lower limit assay quantification 50 ng/ml ; 3-4 weeks postpartum Cressey TR. JAIDS 2005; 38: SD NVP covering the tail ; ZDV/3TC 7 days : reduce resistance from 60 % to % TOPH Trial, SA

28 Two drugs regimen Short course AZT (28 week)+SD NVP : TR 6.3% (PHPT-2) Short course AZT (28 week)+SD NVP : TR 6.3% (PHPT-2) AZT+ddI (36 wk to 1 wk PP) : TR 6.9% (SIMBA trial) AZT+ddI (36 wk to 1 wk PP) : TR 6.9% (SIMBA trial) AZT+3TC 32 wk add SD NVP : TR 4.7% (Ditrame Plus) AZT+3TC 32 wk add SD NVP : TR 4.7% (Ditrame Plus) AZT 36 wk + SD NVP : TR 6.5% AZT 36 wk + SD NVP : TR 6.5%

29 HAART Depend on immune status of mother 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? Which HAART? -NNRTI based HAART -PI based HAART

30 Toxicities concerned NVP NVP -rash ; women>men (3.7 x) -more common with high CD4 > 250 (10X increase in women) Hepatotoxicity Hepatotoxicity -symptomatic hepatotoxicity ; CD4 250: % -fetal hepatic events ; CD : 0.42%, CD4 >400 : 1.1%) -TRC cohort ; low : high CD4 2.9% versus 7.7%

31

32 5. Factors for selection Mother ChildMedical services

33 Action reports from Thammasat Hospital

34 (. ) (. ) ( ) ( )

35 < 2540 ; no ARV important role of a termination of pregnancy < 2540 ; no ARV important role of a termination of pregnancy ; AZT + SD NVP ; AZT + SD NVP > 2547 ; HAART > 2547 ; HAART

36

37 AZT regimen Prevalence of HIV infection pregnancy in TUH = 1-2 percent Prevalence of HIV infection pregnancy in TUH = 1-2 percent AZT alone = infection rate 3.9 percent AZT alone = infection rate 3.9 percent AZT regimen from other studies ; infection rate 5-8 percent, ACTG 076 protocol = 8% AZT regimen from other studies ; infection rate 5-8 percent, ACTG 076 protocol = 8% Cesarean section = beneficial Cesarean section = beneficial MPH ; still using AZT regimen MPH ; 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) 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 delivery Intrapartum: IV Zidovudine in a 1-hr initial dose of 2 mg/kg, followed by a continuous infusion of 1 mg/kg/hr until delivery Neonates: begin at 8-12 hr after birth, and give syrup at 2 mg/kg every 6 hr for 6 weeks Neonates: begin at 8-12 hr after birth, and give syrup at 2 mg/kg every 6 hr for 6 weeks

39 Regimen MPH Antepartum; 300 mg twice a day, initiating at (28) wk,continue throughout pregnancy (regardless of CD4 count) Antepartum; 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 orally Intrapartum; AZT 300 mg every 3 hr and single dose NVP 200 mg orally Postpartum; AZT 300 mg+3TC 150 mg twice a day for 2 weeks Postpartum; AZT 300 mg+3TC 150 mg twice a day for 2 weeks Neonates; NVP 2 mg/kg single dose and AZT 2 mg/kg every 6 hr for 6 weeks Neonates; NVP 2 mg/kg single dose and AZT 2 mg/kg every 6 hr for 6 weeks Disadvantages (compare to HARRT) : Disadvantages (compare to HARRT) : Higher transmission rate Higher transmission rate High incidence of NVP resistance High incidence of NVP resistance

40 HAART (AZT+3TC+NVP)

41 Triple agents (HARRT) Thammasat Hospital ; transmission rate 1.2 % Triple agents (HARRT) Thammasat Hospital ; transmission rate 1.2 % Other studies ; transmission rate 1-1.5% Other studies ; transmission rate 1-1.5%

42 Regimen : TUH 1. CD4 200 / GA 14 weeks Antepartum; AZT(300)/3TC(150) q 12 hr + NVP(200) OD for 2 wk then AZT(300)/3TC(150) +NVP(200) q 12 hr Antepartum; AZT(300)/3TC(150) q 12 hr + NVP(200) OD for 2 wk then AZT(300)/3TC(150) +NVP(200) q 12 hr Intrapartum; AZT 300 mg q 3 hr and AZT(300)/3TC(150) +NVP(200) q 12 hr Intrapartum; AZT 300 mg q 3 hr and AZT(300)/3TC(150) +NVP(200) q 12 hr Postpartum; AZT(300)/3TC(150) +NVP(200) q 12 hr Postpartum; AZT(300)/3TC(150) +NVP(200) q 12 hr Neonates; AZT 2 mg/kg q 6 hrx6 wk Neonates; AZT 2 mg/kg q 6 hrx6 wk

43 2. CD4 > 200 / GA 28 weeks Antepartum; AZT(300)/3TC(150) q 12 hr + NVP(200) OD for 2 wk then AZT(300)/3TC(150) +NVP(200) q 12 hr Intrapartum; AZT 300 mg q 3 hr and AZT(300)/3TC(150) +NVP(200) q 12 hr Postpartum; AZT(300)/3TC(150) q 12 hr x 14 days, stop NVP Neonates; 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/Nelfinavir(NLF) (250 mg 5 tabs q 12 hr, no need for test dose, no covering tail) AZT/3TC/Efavirenz (GA>24wk) AZT/3TC/Efavirenz (GA>24wk) GPOvir(3TC/d4T/NVP)(follow the protocol AZT/3TC/NVP and test doses NVP for 2 wk) GPOvir(3TC/d4T/NVP)(follow the protocol AZT/3TC/NVP and test doses NVP for 2 wk) In case C/S Start AZT with 30 cc of water since NPO then NPO except medicine with water until delivery and postop care period hr Start AZT with 30 cc of water since NPO then NPO except medicine with water until delivery and postop care period hr For no ANC patients Intrapartum; AntiHIV stat, NVP 200 mg single dose (immediately) and AZT 300 mg q 3 hr regardless of CD4 count Intrapartum; AntiHIV stat, NVP 200 mg single dose (immediately) and AZT 300 mg q 3 hr regardless of CD4 count Postpartum;AZT300/3TC150 q 12 hrx14wk Postpartum;AZT300/3TC150 q 12 hrx14wk Neonates; NVP 2 mg/kg single dose + AZT 2 mg/kg q 6 hr x 6 wk (start immediately) Neonates; 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


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