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)

7. Have the Perinatal HIV guidelines
changed?

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

23. Efavirenz(Sustiva)
 NNRTI
 Pregnancy Category D
 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

28. Special Considerations
 Combination Stavudine and didanosine
◦ Increased risk of steatosis and

29. What are some
pharmacological principles of
Intrapartum HIV care?

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

34. How can the guidelines be applied
clinically?

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

39. Questions?

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