PERINATAL HIV. AIIMS- NICU protocols Sunil Saharan 1, Rakesh Lodha 2, Ramesh Agarwal 2, Ashok Deorari 3, Vinod Paul 3 1

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1 PERINATAL HIV Sunil Saharan 1, Rakesh Lodha 2, Ramesh Agarwal 2, Ashok Deorari 3, Vinod Paul 3 1 Senior resident, 2 Assistant Professor, 3 Professor Division of Neonatology, Department of Pediatrics All India Institute of Medical Sciences Ansari Nagar, New Delhi Address for correspondence: Dr Ramesh Agarwal Assistant Professor Department of Pediatrics All India Institute of Medical Sciences

2 2 Ansari Nagar, New Delhi

3 3 Abstract HIV pandemic is one of the most serious health crises the world faces today. Approximately 5-10% of all cases of HIV are children. Majority of children acquire infection through mother-to-child transmission either during pregnancy, delivery, or by breast-feeding. MTCT can be reduced to <2% by antiretroviral prophylaxis to women during pregnancy and labour and to the infant in the first weeks of life, obstetrical interventions including elective caesarean delivery and complete avoidance of breastfeeding. Guidelines for postnatal diagnosis of HIV infection, feeding, immunization and administration of cotrimoxazole prophylaxis have been described in the protocol. Keywords: HIV, pregnancy, perinatal, mother-child transmission, neonate

4 4 1. Introduction: The human immunodeficiency virus (HIV) pandemic is one of the most serious health crises the world faces today. AIDS has killed more than 25 million people since 1981 and an estimated 33.2 million people are now living with HIV, about 2.5 million of whom are children (1). In 2007 alone, an estimated 420,000 children were newly infected with HIV (1). In India estimated 2.47 million (2-3.1million) people are living with HIV infection as on year Adult prevalence of HIV infection in our country is 0.36% ( %). The prevalence rate for females is 0.29 percent, while for males it is 0.43 percent. Prevalence of HIV in pregnant women population was observed to be 0.60% (2). 2. Mode of transmission Most children living with HIV acquire the infection through motherto-child transmission (MTCT). HIV infection can be transmitted from an infected mother to her fetus during pregnancy, during delivery, or by breast-feeding. HIV can be transmitted to the fetus as early as the first and second trimester of pregnancy. However, maternal transmission to the fetus occurs most commonly in the perinatal period. Perinatal transmission is an extremely important form of transmission of HIV infection in developing countries. 3. Risk factors for Perinatal HIV transmission (3)

5 5 Viral factors: High viral load, non syncytium inducing phenotype, HIV 1 Maternal factors: Advanced disease (low CD4 count, symptoms of AIDS), primary infection of mother during pregnancy, first of twins, rupture of membranes more than four hrs, maternal bleeding, mother not on antiretroviral therapy, vaginal delivery, other sexually transmitted diseases, isolated HIV-1 infection Fetoplacental factors: chorioamnionitis, placenta previa, prematurity (increased peripartum transmission) Infant factors: HLA concordance with mother Postnatal factors: breast feeding, higher breast milk virus load, mastitis or maternal nipple lesions, maternal seroconversion during breastfeeding, infant having thrush at less than six month age (in breastfeeding infant) 4. Prevention of perinatal HIV In the absence of any intervention the risk of perinatal transmission is 15 30% in non-breastfeeding populations. Breastfeeding by an infected mother increases the risk by 5 20% to a total of 20 45% (4). The risk of MTCT can be reduced to under 2% by interventions that include antiretroviral (ARV) prophylaxis given to women during pregnancy and labour and to the infant in the first weeks of life, obstetrical interventions

6 6 including elective caesarean delivery (prior to the onset of labour and rupture of membranes), and complete avoidance of breastfeeding (5-7). 5. ARV regimens for treating pregnant women (8) Refer to figure-1. Recommended regimen for pregnant women with indication for antiretroviral therapy (ART) is combination of zidovudine (AZT), lamivudine (3TC) and nevirapine (NVP) in antepartum, intrapartum and postpartum period. Recommended regimen for pregnant women who are not eligible for ART, but for preventing MTCT is: o o Antepartum: AZT starting at 28 weeks of pregnancy Intrapartum: a combination of single dose (Sd) NVP, AZT and 3TC o Postpartum: a combination of AZT and 3TC for 7 days. Recommended regimen for pregnant women who are in labour and have not received ART is: o o Intrapartum: a combination of Sd-NVP, AZT and 3TC Postpartum: a combination of AZT and 3TC 7 weeks Omission of the Sd-NVP for the mother may be considered for women who receive at least four weeks of AZT before delivery.

7 7 When Sd-NVP is used to prevent MTCT, either alone or in combination with AZT, the rationale of giving AZT and 3TC intrapartum and for seven days postpartum is to prevent resistance to NVP. 6. ARV regimens for infants born to HIV positive mothers (8) The recommended regimen for infants is Sd-NVP + AZT for one week. When delivery occurs within two hours of a woman taking Sd-NVP, the infant should receive Sd-NVP immediately after delivery and AZT for four weeks. If the mother receives less than four weeks of antenatal ART, then four weeks rather than one week of AZT is recommended for the infant.

8 8 7. Intrapartum interventions Avoid ARM unless medically indicated. Delivery by elective caesarean section at 38 weeks before onset of labour and rupture of membranes. Avoid procedures increasing risk of exposure of child to maternal blood and secretions like use of scalp electrodes. 7. Breast feeding Breast-feeding is an important modality of transmission of HIV infection in developing countries. The risk of HIV infection via breast-feeding is highest in the early months of breast-feeding (9). Factors that increase the likelihood of transmission include detectable levels of HIV in breast milk, the presence of mastitis and low maternal CD4+ T cell count. Exclusive breast-feeding has been reported to carry a lower risk of HIV transmission than mixed feeding (9). According to current UN recommendations (WHO, 2001) when replacement feeding is acceptable, feasible, affordable, sustainable and safe (AFASS), avoidance of all breastfeeding by HIV-infected mothers is recommended. Otherwise exclusive breastfeeding is recommended during the first months of life.

9 9 WHO recommends that the transition between exclusive breastfeeding and early cessation of breastfeeding should be kept as short as possible, -"early and abrupt cessation (10) - bearing in mind that mixed feeding during this period carries a 70% greater risk of MTCT. Replacement feeding should be given by katori spoon. 8. Postnatal Diagnosis of HIV Infection (11) Refer to figure-2 In children younger than 18 months diagnosis of HIV infection is based on: a positive virological test at 6 weeks for HIV or its components (HIV-RNA or HIV-DNA or HIV p24 antigen) confirmed by a second virological test obtained from a separate determination taken more than four weeks after the first one (12) If an infant or child is breastfeeding, he or she remains at risk of acquiring HIV infection throughout the breastfeeding period. Virological assays to detect HIV infection should be conducted at least six weeks or more after the complete cessation of breastfeeding to rule out HIV infection. Positive antibody testing is not recommended for definitive or confirmatory diagnosis of HIV infection in children until 18 months of age. 9. Co-trimoxazole prophylaxis

10 10 Co-trimoxazole prophylaxis is recommended for all HIV-exposed infants under age 18 months starting at 4 6 weeks of age or when first seen and continued until HIV infection can be excluded (13). Co-trimoxazole prophylaxis is also recommended for a breastfeeding child of any age, continued until HIV infection can be excluded following cessation of breastfeeding, with testing performed six weeks or more after breastfeeding was stopped. In children < 6 month dose is 2.5 ml once a day (trimethoprim 40 mg & sulphamethoxazole 200 mg/ 5 ml) 10. Immunization (14) HIV exposed or infected but asymptomatic children should receive all standard vaccines as per national schedule. HIV infected children with immune suppression or symptoms should receive all standard vaccines except varicella, BCG and OPV vaccines. Consider HiB and pneumococcal vaccines in all HIV exposed children (irrespective of symptoms or CD4 count)

11 11 References 1. UNAIDS/WHO. AIDS Epidemic Update. December National AIDS Control Organization. HIV Sentinel Surveillance Report (HSS-2005). 3. Peter L Havens, David Waters. Management of the infant born to a mother with HIV infection. Pediatr Clin North Am 2004; 51: De Cock KM, Fowler MG, Mercier E, de Vincenzi I, Saba J, Hoff E, Alnwick DJ, Rogers M, Shaffer N. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283(9): European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clinical Infectious Diseases, 2005, 40: Dorenbaum A, Cunningham CK, Gelber RD, Culnane M, Mofenson L, Britto P, Rekacewicz C, Newell ML, Delfraissy JF, Cunningham- Schrader B, Mirochnick M, Sullivan JL; International PACTG 316 Team. Two-dose intrapartum/ newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA 2002; 288(2): Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose Perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004; 351: WHO. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants: towards universal access Magoni M, Bassani L, Okong P, Kituuka P, Germinario EP, Giuliano M, Vella S. Mode of infant feeding and HIV infection in children in a program for prevention of mother-to-child transmission in Uganda. AIDS 2005; 19(4): Preble E A, Piwoz E. Mother-to-child-transmission of HIV in Africa: A framework for prevention Draft document 2001.

12 WHO. Antiretroviral therapy of HIV infection in infants and children: towards universal access Sherman GG, Cooper PA, Coovadia AH, Puren AJ, Jones SA, Mokhachane M, Bolton KD. Polymerase chain reaction for diagnosis of human immunodeficiency virus infection in infancy in low resource settings. Pediatr Infect Dis J 2005; 24(11): WHO. Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults in resourcelimited settings recommendations for a public health approach Indian Academy of Pediatrics. Update on Policies, Guidelines and Recommendations on Immumnization. 2001

13 13 Figure 1 Protocol on approach to a baby born to HIV infected mother 8 HIV infected mother: diagnosed by ELISA test Clinical assessment and CD4 count of mother mother No indication of ART for the ART indicated for mother ART for preventing MTCT Three drug ART AZT + 3TC + NVP AZT starting at 28 weeks Intrapartum Sd-NVP + AZT+3TC Postpartum AZT+3TC 7 days Baby born to HIV positive mother 1. Check antenatal ART (drugs, duration, and compliance) 2. Caesarean / normal delivery 3. Check for PROM 4. Intrapartum ART given or not Mother on antepartum ART Only intrapartum ART No antepartum/intrapartum ART Infant: Sd-NVP + AZT 7 days Infant: Sd-NVP + AZT 4 weeks Infant: Sd-NVP immediately after birth + AZT 4weeks

14 14 Note: If the mother receives less than four weeks of AZT before delivery, the AZT dose for the infant should be extended to four weeks When delivery occurs within two hours of a woman taking Sd-NVP, the infant should receive Sd-NVP immediately after delivery and AZT for four weeks Abbreviations:ART - Antiretroviral therapy AZT - Zidovudine (4 mg/kg twice a day) Sd NVP - Single dose nevirapine (2 mg/kg)

15 15 Figure 2 Diagnostic approach for HIV exposed infants 11 Neonate born to HIV infected mother HIV testing by DNA PCR at or around 6 week age Positive Negative Repeat DNA PCR immediately on a different blood sample If positive, confirms HIV infection (Perform antibody testing after 18 month of age) Repeat test If breastfed: 6-8 wk after cessation of breastfeeding If not breastfed: at 4-6 month age If negative, No HIV infection (Perform antibody testing after 18 month)