HIV Treatment and the Pregnant
    HIV-1 Positive Woman




     Presented By: DeShawndre Bridley
 6th Year Doctorate of P...
Objectives
    Why are we particularly concerned with treatment of
    a pregnant HIV(+) woman?
)   Have the Perinatal HIV...
Why are we particularly
concerned with treatment of a
pregnant HIV(+) woman?
Factors to Consider in the Pregnant
       HIV Infected Woman

2. Antiretroviral treatment of the maternal
   HIV infectio...
AIDS cases due to the perinatal transmission of
HIV infection, by year of diagnosis, 2001–2005,
United States
Race/ethnicity of children (<13 years) with
AIDS diagnosed during 2005 (includes all
children with a diagnosis of AIDS, no...
Have the Perinatal HIV guidelines
changed?
Updated Perinatal Guidelines
   Updated as of Nov. 2, 2007
         Available at http://AIDSinfo.nih.gov
   Updated/New...
Background (I don’t remember how
to HIV is treated! Matter of fact,
What is HIV?!)
Background
   What is HIV-1?
    ◦ Human Immunodeficiency Virus Type 1 is a human
      retrovirus that infects predomina...
Background
   What is HAART?
    ◦ Highly Active Antiretroviral Therapy
    ◦ Consists of a minimum of three antiretrovir...
Background
 What is a NRTI?
 Nucleoside/Nucleotide analog reverse
  transcriptase inhibitor
    ◦ MOA: constrain HIV rep...
Background
 What is a NNRTI?
 Non-nucleoside reverse transcriptase
  inhibitor
    ◦ MOA: bind noncompetitively to rever...
Background
 What is a PI
 Protease Inhibitor
    ◦ MOA: Blocks the action of viral protease required for protein
      p...
Newer Agents
   Entry Inhibitors
    ◦ Enfuvirtide (Fuzeon)
      Pregnancy category B
    ◦ Maraviroc (Selzentry)
     ...
What are some pharmacological
principles of Antepartum HIV
care?
Antepartum Care
   Initiating HAART therapy in a HIV
    positive pregnant woman with at or after
    14 weeks gestation
Pharmacokinetic Changes in the
Pregnant woman
 Gastrointestinal transit time is decreased
 Decreased plasma protein conc...
Protease Inhibitor Therapy and
Hyperglycemia
 Hyperglycemia, new-onset diabetes
  mellitus, exacerbation of existing
  di...
Considerations
   Nelfinavir (Viracept) should not be
    offered
    ◦ Pregnant patients already on nelfinavir should
  ...
Nevirapine(Viramune) and Hepatic/
Rash Toxicity
   Pregnancy category B
   NNRTI
       Single dose at the time of labo...
Delavirdine (Rescriptor)
 NNRTI
 Pregnancy Category C
 Increased risk of ventricular septal
  defects in rodents
 NOT ...
Efavirenz(Sustiva)

 NNRTI
 Pregnancy Category D
 NOT RECOMMENDED IN
  PREGNANCY
Mitochondrial Toxicity and NRTI
drugs
 The relative potency of the nucleosides in
  inhibiting mitochondrial gamma DNA
  ...
Tenofovir
 Potential fetal bone defects
 Potential nephrotoxicity
 Use as a component of maternal
  combination regimen...
Zalcitabine (Hivid)
 Increased risk of hydrocephalus at high
  doses in rodents
 NOT RECOMMENDED IN
  PREGNANCY
 Remove...
Special Considerations
   Antiretroviral Registry
    ◦ Any woman exposed to ART should be
      reported to www.APRegist...
Special Considerations
   Combination Stavudine and didanosine
    ◦ Increased risk of steatosis and
What are some
pharmacological principles of
Intrapartum HIV care?
Lesson From Clinical Trials:
PACTG 076 (Pediatric AIDS Clinical
Trials Group)

   Demonstrated that the administration of...
What is 3 part Zidovudine(ZDV)

   Oral ZDV initiated at 14 to 34 weeks
    gestation and continued throughout
    pregna...
Considerations
 Studies have shown that single dose
  Nevirapine alone or in combination with
  ZDV is effective in reduc...
Special Considerations
   Cesarean Delivery is recommended for
    women with viral loads greater than 1000
    copies/ml
How can the guidelines be applied
clinically?
Clinical Scenario 1
   HIV-1 infected woman who is antiretroviral
    naïve and has indications for antiretroviral
    th...
HAART Regimen Considerations
 Avoid EFV or other teratogenic drugs and
  combinations (d4T/ddl) in first trimester
 Avoi...
Scenario 2
   HIV infected woman in labor who has not
    received antiretroviral treatment prior to
    labor!!!!!
    1...
Scenario 2
   Alternative
    1. ZDV given as a continuous infusion during
       labor, PLUS a single dose of NVP 200mg
...
Questions?
References
   Perinatal HIV Guidelines Working Group. Public Health Service Task
    Force Recommendations for Use of Ant...
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HIV Pharmacotherapy in Pregnancy

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HIV Pharmacotherapy in Pregnancy

  1. 1. HIV Treatment and the Pregnant HIV-1 Positive Woman Presented By: DeShawndre Bridley 6th Year Doctorate of Pharmacy Candidate Florida A&M University
  2. 2. Objectives Why are we particularly concerned with treatment of a pregnant HIV(+) woman? ) Have the Perinatal HIV guidelines changed? a Background (I don’t remember how to HIV is treated! Matter of fact, What is HIV?!) W What are some pharmacological principles of Antepartum HIV care? a What are some pharmacological principles of Intrapartum HIV care? c How can the guidelines be applied clinically?
  3. 3. Why are we particularly concerned with treatment of a pregnant HIV(+) woman?
  4. 4. Factors to Consider in the Pregnant HIV Infected Woman 2. Antiretroviral treatment of the maternal HIV infection 3. Antiretroviral Chemoprophylaxis to reduce the risk of perinatal transmission of HIV
  5. 5. AIDS cases due to the perinatal transmission of HIV infection, by year of diagnosis, 2001–2005, United States
  6. 6. Race/ethnicity of children (<13 years) with AIDS diagnosed during 2005 (includes all children with a diagnosis of AIDS, not just those who contracted HIV perinatally)
  7. 7. Have the Perinatal HIV guidelines changed?
  8. 8. Updated Perinatal Guidelines  Updated as of Nov. 2, 2007  Available at http://AIDSinfo.nih.gov  Updated/New Sections ◦ Lessons From Clinical Trials ◦ Antepartum management ◦ Intrapartum management ◦ Postpartum management ◦ Infant Management
  9. 9. Background (I don’t remember how to HIV is treated! Matter of fact, What is HIV?!)
  10. 10. Background  What is HIV-1? ◦ Human Immunodeficiency Virus Type 1 is a human retrovirus that infects predominantly lymphocytes that bear the CD4 surface protein ◦ Over time immune dysfunction gives rise to AIDS (Acquired Immunodeficiency Syndrome) which is characterized by development of opportunistic infections, malignancies, and wasting ◦ The virus is transmitted sexually or parenterally, and perinatally
  11. 11. Background  What is HAART? ◦ Highly Active Antiretroviral Therapy ◦ Consists of a minimum of three antiretroviral drugs  Potent HAART regimen typically includes two NRTIs plus one or two Pis or an NNRTI
  12. 12. Background  What is a NRTI?  Nucleoside/Nucleotide analog reverse transcriptase inhibitor ◦ MOA: constrain HIV replication by incorporating into elongating strand DNA, causing chain termination ◦ Associated with Lactic Acidosis presumably related to mitochondrial toxicity  Didanosine, Emtricitabine, Tenofovir  Pregnancy category B
  13. 13. Background  What is a NNRTI?  Non-nucleoside reverse transcriptase inhibitor ◦ MOA: bind noncompetitively to reverse transcriptase ◦ Side effects include rash, increased ALT and AST, and Stevens-Johnson syndrome (more likely with nevirapine) ◦ CNS side effects are commonly experienced with efavirenz (sleepiness, vivid dreams, dizziness)
  14. 14. Background  What is a PI  Protease Inhibitor ◦ MOA: Blocks the action of viral protease required for protein processing late in the viral cycle ◦ Most common side effect is GI intolerance ◦ These agents are associated with glucose intolerance, increased cholesterol and triglycerides, and body fat redistribution ◦ Potent CYP 450 inhibitors  Several Drug interactions  Atazanavir, Saquinavir, Nelfinavir**  Pregnancy Category B
  15. 15. Newer Agents  Entry Inhibitors ◦ Enfuvirtide (Fuzeon)  Pregnancy category B ◦ Maraviroc (Selzentry)  Pregnancy category B  Integrase Inhibitors ◦ Raltegravir (Isentress)  Pregnancy category C
  16. 16. What are some pharmacological principles of Antepartum HIV care?
  17. 17. Antepartum Care  Initiating HAART therapy in a HIV positive pregnant woman with at or after 14 weeks gestation
  18. 18. Pharmacokinetic Changes in the Pregnant woman  Gastrointestinal transit time is decreased  Decreased plasma protein concentrations  Increased renal sodium reabsorption  Changes in liver enzymatic metabolic pathways  Body water and fat increase ◦ Increased cardiac output ◦ Increased ventilation ◦ Increased renal and liver blood flow
  19. 19. Protease Inhibitor Therapy and Hyperglycemia  Hyperglycemia, new-onset diabetes mellitus, exacerbation of existing diabetes, and diabetic ketoacidosis have been reported  Pregnancy itself is a risk factor for hyperglycemia  Recommended to perform glucose tolerance testing between 24 to 28 weeks gestation
  20. 20. Considerations  Nelfinavir (Viracept) should not be offered ◦ Pregnant patients already on nelfinavir should be switched to another agent ◦ 9/2007 Pfizer sent out a letter to providers regarding the presence of EMS (ethyl methane sulfonate) in it’s product Viracept  Process related impurity  EMS is mutagenic, carcinogenic, and teratogenic
  21. 21. Nevirapine(Viramune) and Hepatic/ Rash Toxicity  Pregnancy category B  NNRTI  Single dose at the time of labor has been shown to decrease perinatal transmission of HIV  Increases in ALT and AST levels associated with toxicity may be seen during the first 18 weeks of treatment  Monitor transaminases at baseline, every two weeks for the first month, monthly through month 4, and every 1 to 3 months thereafter  More common in women  Risk varies with CD4 count  CD4 count >250 cells/mcl  Signs and Symptoms  Fatigue, malaise, anorexia, nausea, jaundice, liver tenderness, hepatomegaly  Can occur with or with elevated transaminases
  22. 22. Delavirdine (Rescriptor)  NNRTI  Pregnancy Category C  Increased risk of ventricular septal defects in rodents  NOT RECOMMENDED IN PREGNANCY
  23. 23. Efavirenz(Sustiva)  NNRTI  Pregnancy Category D  NOT RECOMMENDED IN PREGNANCY
  24. 24. Mitochondrial Toxicity and NRTI drugs  The relative potency of the nucleosides in inhibiting mitochondrial gamma DNA polymerase in vitro is highest for zalcitabine(ddC), followed by didanosine (ddl), stavudine (d4T), ZDV, 3TC, abacavir (ABC), and tenofovir  Neuropathy, myopathy, cardiomyopathy, pancreatitis, hepatic steatosis, and lactic acidosis
  25. 25. Tenofovir  Potential fetal bone defects  Potential nephrotoxicity  Use as a component of maternal combination regimens only after careful consideration of other alternatives
  26. 26. Zalcitabine (Hivid)  Increased risk of hydrocephalus at high doses in rodents  NOT RECOMMENDED IN PREGNANCY  Removed from the market but still included in the updated guidelines
  27. 27. Special Considerations  Antiretroviral Registry ◦ Any woman exposed to ART should be reported to www.APRegistry.com  Resistance testing should be performed on all pregnant HIV (+) women who are treatment naïve  Resistance testing should be performed in women who are treatment experienced but have not achieved optimal viral suppression
  28. 28. Special Considerations  Combination Stavudine and didanosine ◦ Increased risk of steatosis and
  29. 29. What are some pharmacological principles of Intrapartum HIV care?
  30. 30. Lesson From Clinical Trials: PACTG 076 (Pediatric AIDS Clinical Trials Group)  Demonstrated that the administration of 3 part ZDV to the mother and her infant child could reduce perinatal transmission of HIV by 70% in 2004
  31. 31. What is 3 part Zidovudine(ZDV)  Oral ZDV initiated at 14 to 34 weeks gestation and continued throughout pregnancy ◦ 300mg PO BID or 200mg PO TID  IV ZDV during labor  Oral administration of ZDV to infant for 6 weeks after delivery
  32. 32. Considerations  Studies have shown that single dose Nevirapine alone or in combination with ZDV is effective in reducing the risk of perinatal HIV transmission  d4T (stavudine) can be used during pregnancy but should be discontinued while ZDV is administered IV started at labor  Antagonistic drug interaction
  33. 33. Special Considerations  Cesarean Delivery is recommended for women with viral loads greater than 1000 copies/ml
  34. 34. How can the guidelines be applied clinically?
  35. 35. Clinical Scenario 1  HIV-1 infected woman who is antiretroviral naïve and has indications for antiretroviral therapy 1. Drug Resistance Testing 2. Initiate HAART Regimen 3. During Labor-ZDV intravenous continuous infusion; continue other agents orally 4. Scheduled cesarean delivery at 38 weeks if plasma HIV RNA >1000 copies/ml near time of delivery 5. Give infant ZDV for 6 weeks starting within 6-12 hours after birth
  36. 36. HAART Regimen Considerations  Avoid EFV or other teratogenic drugs and combinations (d4T/ddl) in first trimester  Avoid Nelfinavir until further notice  Use ZDV if feasible  NVP can be used as a component of HAART for women with CD4 count ≤250 cells/mm3, but should only be used as a component of therapy in women with CD4 counts >250 cells/ mm3 if the benefit clearly outweighs the risk due to an increased risk of severe hepatotoxicity.
  37. 37. Scenario 2  HIV infected woman in labor who has not received antiretroviral treatment prior to labor!!!!! 1. Give mother ZDV 2mg/kg IV over 1hr, followed by continuous infusion of 1mg/kg/hr during labor until delivery 2. Give infant ZDV for six weeks starting within 6 to 12 hours after birth  Infant <35 weeks gestation: 1.5mg/kg/dose IV  Infant >35 weeks gestation: 2mg/kg/dose PO q 12h advancing to q8h at two weeks of age if ≥ 30 weeks gestation at birth or at 4 weeks if of age if <30 weeks at birth
  38. 38. Scenario 2  Alternative 1. ZDV given as a continuous infusion during labor, PLUS a single dose of NVP 200mg PO at the start of labor 2. Give infant single dose NVP 2mg/kg PO at 2-3 days of birth if mother received single dose NVP at start of labor (give at birth if mother did not receive NVP at start of labor) and ZDV for 6 weeks starting within 6 to 12 hours after birth
  39. 39. Questions?
  40. 40. References  Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV- Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. November 2, 2007 1-96. Available at: http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf  The Washington Manual of Medical Therapeutics 32nd Edition

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