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. 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. Why are we particularly
concerned with treatment of a
pregnant HIV(+) woman?
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. AIDS cases due to the perinatal transmission of
HIV infection, by year of diagnosis, 2001–2005,
United States
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)
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. Background (I don’t remember how
to HIV is treated! Matter of fact,
What is HIV?!)
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. 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. 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. 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. 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. Newer Agents
Entry Inhibitors
◦ Enfuvirtide (Fuzeon)
Pregnancy category B
◦ Maraviroc (Selzentry)
Pregnancy category B
Integrase Inhibitors
◦ Raltegravir (Isentress)
Pregnancy category C
16. What are some pharmacological
principles of Antepartum HIV
care?
17. Antepartum Care
Initiating HAART therapy in a HIV
positive pregnant woman with at or after
14 weeks gestation
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. 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. 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. 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. Delavirdine (Rescriptor)
NNRTI
Pregnancy Category C
Increased risk of ventricular septal
defects in rodents
NOT RECOMMENDED IN
PREGNANCY
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. Tenofovir
Potential fetal bone defects
Potential nephrotoxicity
Use as a component of maternal
combination regimens only after careful
consideration of other alternatives
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. 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
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. 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. 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. Special Considerations
Cesarean Delivery is recommended for
women with viral loads greater than 1000
copies/ml
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. 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. 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. 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
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