Integrative Activity: HIV

1. Integrative Activity: HIV Baluyut, G.T., Benavidez, R.E.E., Chua, M.F.P., Del Prado, V. F., Dela Cruz, C. D., Parco, M.D.S., Pascua, R.C. Sacdalan, C.P. Tsai, K., Tud, A.R.,& Villarete, N.R.T. (2011)

2. Evaluation and management of RS Question 1:

3. Salient Features History: • R.S., 36 year old female residing in Quezon City • OB Score: G2P2 (2,0,0,2) • January 2, 2011- gave birth via C-section due to fetal distress • Didn’t have prenatal check-ups • Had Recurrent Urinary tract infections • G1: (2007), girl, delivered via NSD at a lying in clinic in QC, no perinatal/ neonatal complications, baby was breastfed for one year • Married for 8 years to a seafarer who goes home to the Philippines 1-2x/year

4. Salient Features History: • G2 • 38 weeks AOG • male infant via primary caesarian section due to fetal distress at a government hospital last January 2, 2011 • Upon birth: APGAR Score of 9/10 • Birth weight: 2600g (Normal is 3400g) • Birth length: 50 cm • Normal physical examination findings

5. Salient Features Physical Examination: • Whitish plaques on the tongue • (+) CLAD • Yellowish vaginal discharge on internal examination Laboratory tests • HIV screening positive • CD4 Count = 180

6. Points to Consider • RS is HIV screening positive with CD4 of 180 • It’s not elaborated if she had a confirmatory test done. • She gave birth last January 2, 2011 • This means that we will only be managing RS’s HIV and we will not be able to do intrapartum prophylaxis anymore. • RS has a baby girl which she breastfed for one year. • This might have implications in prevention of MTCT of HIV.

7. Evaluation • Clinical categories of HIV Infection: • Category A: Consists of > 1 of the ff conditions in an adolescent or adult (>13 years) with documented HIV infection. Conditions listed in categories B and C must not have occurred. • Asymptomatic HIV infection • Persistent generalized lymphadenopathy • Acute (primary) HIV infection with accompanying illness or history of acute HIV infection

8. Evaluation 2.Category B: With > 1 of the following criteria: (1) conditions attributed to HIV infection or indicate defect in cell-mediated immunity; or (2) the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection

9. Evaluation 2. Category B

10. Evaluation 3. Category C – with conditions listed in the AIDS surveillance case definition

11. Evaluation 3. Category C

12. Classification

13. Evaluation of RS • Physical Examination: • Whitish plaques on the tongue (oral leukoplakia) • (+) CLAD • Yellowish vaginal discharge on internal examination (vulvovaginal candidiasis) *patient is most likely fall under category B because she was already symptomatic but does not manifest conditions under category C

14. Evaluation of RS • Laboratory: • HIV screening positive • CD4 Count = 180 (class 3) *further classifying the patient into class B3

15. Initial Evaluation

16. Diagnostics • ELISA or Enzyme immunoassay • standard blood screening test for HIV • Sensitivity is 95%, but less specific compared to western blot test • Detect both HIV-1 and HIV-2 • False positives to antibodies to class II antigens, autoantibodies, hepatic disease, recent influenza vaccination, and acute viral infections

17. Diagnostics •  Western Blot • Most common confirmatory test • Criteria (U.S. FDA in 1993): Positive Western blot if two of the three HIV proteins: p24, gp41, and gp120/160 were identified.

18. Diagnostics •   P24 antigen capture assay • Measurement of levels of HIV-1 core protein in an EIA-based format following dissociation of antigen-antibody complexes by weak acid treatment • Direct detection of HIV • PCR • PCR amplification of cDNA generated from viral RNA (target amplification) • Direct detection of HIV

19. Diagnostics •   bDNA • Measurement of levels of particle-associated HIV RNA in a nucleic acid capture assay employing signal amplification • Direct detection of HIV • Nuclisens • Isothermic nucleic acid amplification with internal controls • Direct detection of HIV

20. Algorithm

21. Monitoring • CD4+ T Cell Counts (flow cytometry) • best indicator of the immediate state of immunologic competence of the patient with HIV infection • CD4+ T cell counts <200/L - high risk for P. jiroveci, • CD4+ T cell counts <50/L - high risk of disease from CMV, mycobacteria of the M. avium complex (MAC) and/or T. gondii

22. Monitoring • CD4+ T Cell Counts (flow cytometry) • Should have CD4+ T cell measurements performed at the time of diagnosis and every 3–6 months thereafter. • CD4 T cell count <350/L is an indication for consideration of initiating ARV therapy • Decline in CD4+ T cell count of >25% is an indication for considering a change in therapy. Once the CD4+ T cell count is <200/L, patients should be placed on a regimen for P. jiroveci prophylaxis, and once the count is <50/L, primary prophylaxis for MAC infection is indicated.

23. Evaluation in Pregnant Patients • HIV screening should be a routine component of preconception care, maximizing opportunities for all women to know their HIV status before conception. • Screening early in pregnancy enables HIV-infected women and their infants to benefit from appropriate and timely interventions (e.g., antiretroviral medication, scheduled cesarean delivery, and avoidance of breastfeeding). • HIV screening should be included in the routine panel of prenatal screening tests for all pregnant women. Patients should be informed that HIV screening is recommended for all pregnant women and that it will be performed unless they decline (opt-out screening).

24. Evaluation in Pregnant Patients • Repeat HIV testing in the third trimester, preferably in <26 weeks AOG, is recommended for all women at risk for HIV or AIDS or showing signs of HIV /AIDS • Rapid HIV testing should be performed for all women in labor who do not have documentation of results from an HIV test during pregnancy. Patients should be informed that HIV testing is recommended for all pregnant women and will be performed unless they decline (opt-out screening). Immediate initiation of appropriate antiretroviral prophylaxis should be recommended on the basis of a reactive rapid HIV test result, without awaiting the result of confirmatory testing. • In postpartum setting, if status is not know at time of delivery, mother should be screened immediately postpartum with rapid HIV test

25. Management • WHO Guideline: • Women who need ARV treatment for their own health should receive it in accordance with the WHO guidelines on ARV treatment.

26. HIV and Pregnancy • Steps to prevent transmitting an HIV infection: • Using antiviral drugs • having a cesarean section • not breastfeeding your child • lower your infants risk of infection to less than 2%.

27. ARV treatment Guideline: • If CD4 testing is available, WHO recommends offering ARV treatment to adolescents and adults with: • WHO Stage IV disease irrespective of CD4 cell count • WHO Stage III disease with consideration of using CD4 cell counts less than 350 106 cells/L to assist decision making and; • WHO Stages I and II disease in the presence of a CD4 cell count less than 200 106 cells/L.

28. ARV Treatment • The WHO-recommended first-line ARV regimens for adolescents and adults consist of a five-drug formulary, with a triple combination of: • ZDV + 3TC + NVP or • d4T + 3TC + NVP or • ZDV + 3TC + EFV or • d4T + 3TC + EFV. * ZDV (Zidovudine) 3TC (Lamivudine) d4T (Stavudine) EFV (Efavirenz) NVP (Nevirapine)

29. The selection of ARV regimen for women should consider the possibility of a planned or unintended pregnancy and that ARV drugs may be received in the first trimester of pregnancy during the period of organogenesis and before a pregnancy is recognized. • Similarly, the possibility of a future pregnancy should be considered in selecting an ARV regimen for pregnant women.

30. In addition to substantial clinical experience with the use of ZDV among pregnant women and among infants, the efficacy and safety of ZDV prophylaxis have been more extensively studied than those of other ARV drugs. When ARV treatment is initiated during pregnancy, ZDV should therefore be included in the regimen whenever possible.

31. Among women of childbearing potential or pregnant women who are eligible for ARV treatment, based on the same criteria as for non-pregnant women, the first-line ARV regimens are ZDV + 3TC + NVP or d4T + 3TC + NVP. • The NNRTI component of these regimens is NVP, which is a potent drug with demonstrated clinical efficacy, is relatively easy to use and is available as part of a three-drug fixed-dose combination.

32. Alternative ARV drugs have limitations. EFV, an NNRTI drug, is considered potentially teratogenic and is not recommended in the first trimester of pregnancy. • If EFV has to be used, then it should only be taken after the first trimester of pregnancy and avoided among women of childbearing age unless effective contraception can be ensured. Among non-pregnant women using effective contraception, EFV remains a viable option for the NNRTI component of the regimen.

33. C-Section • HIV-positive women may have a c-section done at 38 weeks or have a vaginal birth. • lower risk of mother-to-child transmission, it is considered to be major surgery and does have some associated risks. • Recommended for those women whose • viral load at 36 weeks is unknown or more than 1000copies/mL; • have not taken any antiviral drugs or only taken ZDV during their pregnancy; • who have not received any prenatal care prior to 36 weeks gestation.

34. Breastfeeding: • The efficacy of ARV drugs in preventing postnatal transmission during breastfeeding is not yet known. • Because HIV can be transmitted through breast milk, mothers should not breastfeed their baby. Infant formula is a safe and healthy alternative to breast milk for the babies of HIV-infected mothers.

35. Evaluation and management of RS’s baby Question 2:

36. Anti-retroviral Prophylaxis – When to Start • Infants • Initiate ART for all HIV-infected infants diagnosed in the first year of life, irrespective to CD4 count or WHO clinical stage. • Children - Initiate ART for all HIV-infected children between 12 and 24 months of age irrespective of CD4 count or WHO clinical stage. - Initiate ART for all HIV-infected children between 24 and 59 months of age with CD4 count of ≤750 cells/mm3 or %CD4+ ≤25, whichever is lower, irrespective of WHO clinical stage. Taken from – Antiretroviral therapy for HIV infection and children: Towards universal access 2010 by WHO

37. Children (cont’d) • Initiate ART for all HIV-infected children more than 5 years of age with a CD4 count of ≤350 cells/mm3 (as in adults), irrespective of WHO clinical stage. • Initiate ART for all HIV-infected children with WHO clinical stages 3 and 4, irrespective of CD4 count. • Initiate ART for any child less than 18 months of age who has been given a presumptive clinical diagnosis of HIV infection. Taken from – Antiretroviral therapy for HIV infection and children: Towards universal access 2010 by WHO

38. First-line ART regimens for infants and children • Infants For infants not exposed to ARVs, start ART with nevirapine (NVP) + 2 nucleoside reverse tran- scriptase inhibitors (NRTIs). For infants exposed to maternal or infant NVP or other NNRTIs used for maternal treatment or PMTCT, start ART with lopinavir/ritonavir (LPV/r) + 2 NRTIs. For infants whose exposure to ARVs is unknown, start ART with NVP + 2 NRTIs. Taken from – Antiretroviral therapy for HIV infection and children: Towards universal access 2010 by WHO

39. Children For children between 12 and 24 months of age exposed to maternal or infant NVP or other NNRTIs used for maternal treatment or PMTCT, start ART with lopinavir/ritonavir (LPV/r) + 2 NRTIs. For children between 12 and 24 months of age not exposed to NNRTIs, start ART with NVP + 2 NRTIs. For children more than 24 months and less than 3 years of age start ART with NVP + 2 NRTIs. For children 3 years of age and older, start ART with NVP or efavirenz (EFV)-containing regimen + 2 NRTIs. Taken from – Antiretroviral therapy for HIV infection and children: Towards universal access 2010 by WHO

40. Diagnosing HIV Infection in Infants • HIV DNA PCR at 6 to 8 weeks of life • 2 consecutive (+) are diagnostic for infection • Sensitivity 95%, specificity 97% • HIV ELISA at 18 months • If DNA PCR not available • Infant should be constantly monitored • Not used in neonates due to maternal transfer of antibodies

41. Symptoms of HIV Infection in Infants • Recurrent bacterial infections seen commonly in childhood like otitis media, sinusitis, pneumonia • Recurrent viral infections • Fungal infections • Failure to thrive (poor growth) • Developmental delay

42. Prophylaxis against Pneumocystis Jiroveci Pneumonia • Majority of cases happen during the first year of life • Before HIV infection is documented • Before decrease in CD4+ • Recommended even for HIV indeterminate status • Started at 4 to 6 weeks of life • Continued until infant is proven HIV-negative

43. Prophylaxis against Pneumocystis Jiroveci Pneumonia • TMP-SMX, 5mg/kg/day of the TMP component administered orally in divided doses twice daily and administered seven days per week; • TMP-SMX, 5mg/kg/day of the TMP component administered orally divided twice daily and administered three times per week on alternate days (e.g. Monday-Wednesday- Friday); • TMP-SMX, 5mg/kg/day of the TMP component administered orally in divided doses twice daily and administered three times per week on consecutive days (e.g. Monday- Tuesday-Wednesday); • TMP-SMX, 5mg/kg/day of the TMP component administered orally as a single daily dose and administered three times per week on consecutive days (e.g. Monday- Tuesday-Wednesday). • Higher dosing may result to bone marrow toxicity when given daily

44. Immunization • No live vaccines should be given until proven that the infant is HIV-negative • eg. MMR, BCG

45. Evaluation of National Health Programs for HIV Question 3:

46. National Health Programs on Prevention of MTCT of HIV

47. National Health Programs on PMTCT of HIV • Administrative Order No. 2009-0016 by Sec. Francisco T. Duque III on May 20, 2009 • “Policies and Guidelines on the Prevention of Mother to Child Transmission (PMTCT) of Human Imunodeficiency Virus (HIV) • General Objective: To provide policies and guidelines on the prevention of mother to child transmission of HIV that shall be used by health care providers nationwide.

48. National Health Programs on PMTCT of HIV • Ten Components of PMTCT • Information and Education • Basic and essential information on STI, HIV and AIDS • Risk Assessment • For pregnant women with complaints pertaining to the reproductive tract • Multiples sex partners, symptoms of STI, drug use, history of voluntary HIV counseling and testing • STI Case Management - Proper management of women and partners diagnosed with STI based on “Revised National Sexually Transmitted Infections Case Management Guidelines” • HIV Counseling and Testing • Offered to women and partners with one or more risk factors • Informed consent and confidentiality • Counseling on the Prevention of Unintended Pregnancies • Counseling on Family Planning • Information and access to safe and effective contraception methods • Information on PMTCT program and availability of essential care and support services

49. National Health Programs on PMTCT of HIV 6. Referral to Treatment Hubs - Access to proper treatment and care such as ARV - Treatment Hubs: San Lazaro Hospital, PGH, RITM, etc. 7. Anti-Retroviral Treatment and Prophylaxis for HIV-Infected Pregnant Women and Their Newborn - Anti-retroviral Therapy (ART) for eligible HIV infected pregnant women - ARV prophylactic regimen for HIV infected pregnant women with no indication for ART - Newborns of HIV infected pregnant women: ARV prophylactic regimen - Confirmed HIV infected infants: ART based on Guideline on the Integrated Management of Pediatric HIV and AIDS 8. Management of Labor and Delivery of HIV Positive Pregnant Women - Delivery at nearest treatment Hub 9. Counseling of HIV Infected Mothers Regarding Feeding Options for Their Infants - Information on risk and benefits of exclusive breastfeeding and exclusive replacement feeding

50. National Health Programs on PMTCT of HIV 10. Follow-Up, Care, Treatment & Support for Mothers Infected with HIV, Their Children and Families - HIV-related care and ART (when indicated), adherence support, cotrimoxazole prophylaxis, sexual and reproductive health services, diagnosis of HIV infection in infants -Early diagnosis and initiation of treatment for all exposed infants following the Integrated Management of Pediatric HIV and AIDS