In the name of god

1. In the name of god HIV INFECTION

2. HIV INFECTION • The estimated number of perinatally acquired AIDS cases had decreased dramatically over the last two decades. This is predominantly due to the implementation of prenatal HIV testing with antiviral therapy given to the pregnant woman and then to her neonate . • In addition, highlyactive antiretroviral therapy(HAART) has led to an increasing number of people living with chronic HIV infectio

4. Etiopathogenesis • RNA retroviruses :, HIV-1 and HIV-2. • Transmission: sexual intercourse, blood or blood-contaminated products, and mothers may infect their fetuses • The common denominator of clinical illness : profound immunosuppressionthat gives rise to a variety of opportunistic infections and neoplasms. • Sexual transmission occurs when mucosal dendritic cells bind to the HIV envelope glycoprotein gp120

5. Etiopathogenesis • two chemokine receptors—CCR5 and CXCR4 • The CCR5 co-receptor is found on the cell surface of CD4 positive (CD4+) cells in high progesterone states such as pregnancy, possibly aiding viral entry • pregnancy has minimal effects on CD4+ T-cell counts and HIV RNA levels, (the latter are often higher 6 months postpartum than during pregnancy).

6. Clinical Manifestations • The incubation period from exposure to clinical disease is days to weeks. Acute HIV infection is similar to many other viral syndromes and usually lasts less than 10 days. • Common symptoms include fever,N/V, and night sweats, …. • After symptoms abate, the set-point of chronic viremia is established. The progression from asymptomatic viremia to AIDS has a median time of approximately 10 years . • Route of infection, the pathogenicity of the infecting viral strain, the initial viral inoculum, and the immunological status of the host all affect the rapidity of progression

7. Prenatal HIV Screening • The CDCP, ACOG, AAP,…recommend prenatal screening using an opt-out approach. • In areas in which the incidence of HIV or AIDS is 1 per 1000 person years or greater or in women at high risk for acquiring HIV during pregnancy, repeat testing in the 3rdtrimester • (HIGH RISK……..) • Screening is performed using an ELISA test with a sensitivity of >99.5%. • A positive test is confirmed with either a Western blot or (IFA) (high specificity). • Antibody can be detected in most patients within 1 month of infection, and thus, antibody serotesting may not exclude early infection. • For acute primary HIV infection, identification of viral p24 core antigen or viral RNA or DNA is possible. False-positive confirmatory results are rare

8. Strategy for Rapid HIV Testing of Pregnant Women in Labor If the rapid HIV test result in labor‘ and delivery is positive : • 1. Tell the woman she may have HIV infection and that her neonate also may be exposed • 2. Explain that the rapid test result is preliminary and that false-positive results are possible • 3. Assure the woman that a second test is being performed to confirm the positive rapid test result • 4. To reduce the risk of transmission to the infant, immediate initiation of antiretroviral prophylaxis should be recommended without waiting for the results of the confirmatory test • 5. After birth, discontinue maternal antiretroviral therapy pending receipt of confirmatory test results • 6. Teil the women that she should postpone breast feeding until the confirmatory result is available because she should not breast feed if she is infected with HIV • 7. Inform pediatric care providers ,maternal test results ,so that they may institute the appropriate neonatal prophylaxis

9. Maternal and Perinatal Transmission • mother-to-child transmission is the most common cause of pediatric HIV infections. 15 and 40% of neonates born to non-breast-feeding, untreated, HIV-infected mothers are infected. • Vertical transmission is more common with preterm births, especially with prolonged membrane rupture (>4 hr ROM)15% TO 25% • women with maternal HSV-2 antibody had a significant 50% increased risk of intrapartum HIV-1 maternal-to-child transmission.

10. Maternal and Perinatal Transmission • MATERNAL FACTORS: -AIDS (progressive diseas) -low CD4 -High viral load –Primary HIV –Other STD –NVD –Age –Malnutrition( Vit A) –Smoking –Drug abuse • FETAL FACTORS: - Chorioamnionitis –LBW –Prematurity –PROM>4hr –Breast feeding

11. Maternal and Perinatal Transmission • Perinatal HIV transmission is most accurately correlated with maternal plasma HIV RNA burden • 1% with <400 copies/mL, and it was > 30 % with >100,000 copies/mL . • (ZDV) therapy that reduced these levels to <500 copies/mL also minimized the risk of transmission • although ZDV is effective in reducing transmission across all HIV RNA levels. • Maternal infusions of HIV-1 hyperimmune globulin did not alter the risk of transmission. • Transmission, however, has been observed at all HIV RNA levels, including those that were nondetectable by current assays. ( discordance between the viral load in plasma and in the genital secretions). • The viral load should not be used to determine whether to initiate antiretroviral therapy in pregnancy.

14. Maternal and Perinatal Outcomes • Although maternal morbidity and mortality rates are not increased in seropositive asymptomatic women, it appears that adverse fetal outcomes may be increased . • If the CD4+ T-cell count is <200/mm3, primary prophylaxis for P. jiroveci(formerly P. carinii) pneumonia is recommended with sulfamethoxazole-trimethoprim or dapsone. Pneumonitis is treated with oral or intravenous sulfamethoxazole-trimethoprim or dapsone-trimethoprim.

15. Maternal and Perinatal Outcomes • Even with treatment, the incidence of perinatal complications in HIV-infected women is increased. • Adverse fetal outcomes were associated with a CD4+ cell proportion of <15 percent. - preterm birth was 20 % -fetal-growth restriction was 24 %. (adverse outcomes were even more prevalent in developing countries.) • Prenatal exposure to HAART may increase the risk for neonatal neutropenia, although no long-term hematological or hepatic toxicities have been identified • women given combination PI regimens had an increased risk of very-lBW infants. Despite this, combined therapy should not be withheld

16. Preconceptional Counseling • Effective contraception if pregnancy is undesired. • Certain antiviral medications decrease the efficacy of hormonal contraception. • Education for decreasing high-risk sexual behaviors to prevent transmission and to decrease the acquisition of other STD . • High teratogenic potential are avoided if the woman becomes pregnant.( efavirenz ) • Decrease HIV RNA viral load effectively prior to pregnancy.

17. Management DuringPregnancy • · Standard prenatal laboratory surveys : (Cr,CBC, and bacteriuria screening ) • ·Plasma HIV RNA quantification-"viralload" and CD4+ T-lymphocyte count as well as antiretroviral resistance testing • · Serum hepatic transaminase levels • · HSV-1and -2,CMV, toxo, and hepatitis C screening • .Baseline chest radiograph • · Tuberculosis skin testing (PPD) • · Evaluation of need for pneumococcal, hepatitis B, and influenza vaccine · • .Sonographic evaluation to establish gestational age.

18. Antiretroviral Therapy • Treatment is recommended for all HIV-infected pregnant women. • Treatment reduces the risk of perinatal transmission regardless of CD4+ T-cell count or HIV RNA level. • starting HAART regimen is two nucleoside reverse transcriptase inhibitors (NRTIs) plus a (NNRTI) or protease inhibitor(s). • Because of an increased risk of hepatotoxicity, nevirapine is reserved for women with a CD4+ cell count <250 cells/mm3.

20. Recommendations for Antiviral Drug Use During Pregnancy

21. HIV-infected woman on antiretroviral therapywho becomes pregnant • . Continue current medication if viral suppression adequate and patient tolerating • - Avoid efavirenz in the first trimester . • If virus detectable, order HIV antiretroviral drug-resistance testing . If first trimester, continue medications. If stopped, stop all medications and then reinitiate in the second trimester. • .If not receiving zidovudine (ZDV) antepartum, start IV ZDV in labor

22. HIV-infected woman who is antiretroviral na"iveand has maternal indications for HAART • .Order HIV antiretroviral drug-resistance testing . • Initiate HAART: - Avoid efavirenz in the first trimester - Use ZDV-containing regimen if feasible - Avoid nevirapine in women with a CD4+ count>250 cells/mm3 . • HAART should be initiated as early as possible for maternal indications . • If not receiving zidovudineantepartum, start IV ZDV

23. HIV-infected woman who is antiretroviral na"ivewith no maternal indication for HAART • Order HIV antiretroviral drug-resistance testing .Initiate HAART: - Consider delaying therapy until the start of the second trimester (14weeks) - Use ZDV-containing regimen if feasible - Avoid nevirapine in women with a CD4+ count >250 cells/mm3 . ZDV monotherapy is controversial: • - If used, use in women with HIV RNA levels <1000 copies/mL • - If not receiving zidovudineantepartum, start IV ZDVin

24. HIV-infected woman previously on antiretroviralmedications but not on medications currently • . Order HIV antiretroviral drug-resistance testing . • initiate HAART with regimen based on prior therapy history and resistance testing . • Avoid efavirenz in the first trimester . • Use ZDV-containing regimen if feasible . • Avoid nevi rapine in women with a CD4+ count>250 cells/mm3 . • If not receiving zidovudineantepartum, start IV ZDV

25. HIV-infected woman on no antiretroviral medicationwho presents in labor • . Order initial HIV laboratory assessment . • Start zidovudine intravenous protocol . • or . Start intravenous zidovudine plus a single dose of nevirapine(NVP). • if NVP initiated, consider adding lamivudine for 7 days postpartum to decrease NVP resistance .

26. Laboratory Assessment • CD4+ count, HIV RNA viral load ,CBC ,LFT: 4 weeks after beginning or changing therapy to assess responseand evidence of toxicity. • HIV RNA viral load and CD4+ quantification are determined each trimester. • If the HIV RNA viral load increases or does not decrease appropriately, then medication compliance and antiretroviral drug resistance are assessed. • Poor adherence to therapy appears to be a significant problem in pregnancy. • Abnormal GCT and PI use ? • careful surveillance for : interactions between antiretroviral drugs with TX for opportunistic infection, methadone, and TB.

27. Prenatal HIV Transmission • Maternal HAART + intrapartum ZDV prophylaxis has dramatically reduced the perinatal HIV transmission risk from about 25 % to 2 % or less. • Optimal management of labor is uncertain, • If labor is progressing with intact membranes, artificial rupture and invasive fetal monitoring are avoided. • Labor augmentation is used when needed to shorten the interval-to-delivery to further decrease the risk of transmission. • Operative delivery with forceps or vacuum extractor is avoided if possible. • Postpartum hemorrhage is managed with oxytocin and prostaglandin analogs because methergine and other ergot alkaloids interact with reverse transcriptase and protease inhibitors to cause severe vasoconstriction.

28. Prenatal HIV Transmission • Cesarean delivery has been recommended to decrease HIV prenatal transmission. • (8533 mother-neonate pairs) Vertical HIV transmission was reduced by approximately half when C/S was compared with NVD. And when antiretroviral therapy was given in the prenatal, intrapartum, and neonatal periods along with C/S, the likelihood of neonatal transmission was reduced by 87 % compared with other modes of delivery and without antiretroviral therapy. • ACOG concluded that scheduled C/S should be discussed and recommended for HIV-infected women whose HIV-1 RNA load exceeds 1000 copies/mL.(38 weeks ) . • Although data are insufficient to estimate such benefits of cesarean delivery for women whose HIV RNA levels are below 1000 copies/mL, it is unlikely that scheduled cesarean delivery would confer additional risk reduction

29. Pediatric AIDS Clinical Trials Group (PACTG) 076 ZidovudineRegimen • Antepartum : 100 mg orally five times daily, initiated at 14 to 34 weeks and continued throughout pregnancy. • Intrapartum: During labor, IV zidovudine in a 1-hour initial dose of 2 mgjkg, followed by a continuous infusion of 1 mgjkgjhr until delivery. • Neonate: Begin at 8 to 12 hours after birth, and give syrup at 2 mgjkg Q6h for 6 weeks. • IV dosage for infants who cannot tolerate oral intake is 1.5 mgjkg IV Q6h). ( alternative regimens include 200 mg TID or 300 mg BID) • beFor elective C/S, IV zidovudine is begun at least 3 hr prior to surgery. • For PROM or labor with a planned operative delivery, the loading dose may be given over the half hour prior to surgery.

30. Diagnosis of infant HIV status • the first DNA PCR test for HIV : within 48 hours of birth. • Testing of the umbilical cord blood should not be done due to possible risk of contamination with maternal blood. • A positive test will provisionally mean that the newborn infant is infected and further HIV DNA/RNA testing should be undertaken straight away to confirm the diagnosis and enable an early switch from ZDVm to ART. • If negative, further HIV DNA tests at 6 &12 weeks from birth • The third test may be more important if the risk of transmission is considered to be high and ART prophylaxis is prescribed for four weeks. Further investigation of any positive result should be undertaken without delay to allow appropriate early therapy if HIV infection is confirmed.

31. Diagnosis of infant HIV status • Where HIV DNA testing is not available, HIV RNA assays can be used but the pitfalls of both low copy number RNA false positives and negative results during or shortly after infant ART for PMTCT need to be recognized and such results interpreted with caution. • Even for HIV-exposed children testing negative, follow up and documentation of seroreversion by an HIV antibody test is recommended at 15–18 months. • low titres of maternal antibody can be detected even at 15 months in uninfected children and should be interpreted with caution or the test delayed until 18 month

32. BREAST FEEDING • Vertical transmission is increased by breast feeding, and it generally is not recommended in HIV-positive women. • The probability of HIV transmission per liter of breast milk ingested is estimated to be similar in magnitude to heterosexual transmission with unsafe sex in adults

33. Thanks for your attention