HIV Infection and Pregnancy

Oluwatosin Jaiyeoba

Michael J. Kilby

INTRODUCTION

Significant advances have been made in the prevention of mother-to-child HIV transmission (MTCT) to the extent that in countries with access to modest health care resources, it is a reasonable goal that no child should be born with HIV. With the implementation of recommendations for universal prenatal HIV counseling and testing, antiretroviral prophylaxis (including multidrug highly active antiretroviral regimens, rather than monotherapy, for infected mothers), scheduled cesarean delivery, and avoidance of breast-feeding, the rate of perinatal transmission of HIV has dramatically diminished to <2% in the United States and Europe.

EPIDEMIOLOGY

Men and women are equally affected by HIV infection worldwide. However, the United States has consistently experienced a relative increase in the number of HIVinfected women in recent years. In 2009, women accounted for 24% of new US HIV infections.
Fifty-seven percent occurred in African American women, 21 % in Caucasian women, and 16% in Hispanic/Latinas.

ANTIRETROVIRAL THERAPY

Importance of Antiretroviral Therapy

Decreases maternal viral load (VL) in blood and genital secretions, reduces perinatal transmission, and functions as infant preexposure prophylaxis.
Three-part strategy: antepartum, intrapartum, infant prophylaxis.
Three-drug combination therapy is recommended, generally:

2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTI)

PLUS

1 nonnucleoside reverse transcriptase inhibitor (NNRTI)

OR

1 protease inhibitor (PI) boosted with 100 mg oral ritonavir

Consideration Should Be Given to Drug Distribution in Pregnancy

Altered drug pharmacokinetics (PK) during pregnancy
- Placental transport of the drug, compartmentalization of the drug in the embryo/fetus and placenta, biotransformation of the drug by the fetus and placenta, and elimination of the drug by the fetus
Altered drug dosing requirements and susceptibility to toxicity
NRTI and NNRTI have similar PK properties in pregnant and nonpregnant women.
PI show variable PK properties in pregnant women particularly in the second and third trimesters. See Table 5-1.

When to Initiate Antiretroviral Therapy

Always counsel about antiretroviral therapy (ART) use during pregnancy and prevention of perinatal transmission, regardless of plasma HIV RNA levels.
Perform genotypic resistance testing before initiating ART if HIV RNA levels are above the threshold for resistance testing.
Begin ART
- Immediately in women requiring treatment for their own health.
- After the first trimester in women not requiring immediate therapy.
- See Table 5-1 for commonly used preferred and alternative regimens.
Continue ART unchanged in women who become pregnant during therapy
- ART-experienced patients should continue medication unless regimen includes efavirenz, which is not recommended for use in the first trimester and should only be used in the second and third trimesters if there are no alternatives.

Importance of Viral Load and Immune Status on Risk of HIV Transmission

Plasma HIV RNA VL correlates predictably with transmission risk. However, there is no absolute VL threshold below which there is no known risk of transmission.

ANTEPARTUM MANAGEMENT

Management to include the recommendations in Table 5-2 and routine obstetric care following American College of Obstetricians and Gynecologists (ACOG) guidelines.
Monitor CD4 cell count at initial antenatal visit and at least every 3 months.
HIV RNA VL monitoring:
- Initial visit or before initiation of therapy
- Two to four weeks after initiating or changing therapy
- Every 4 to 8 weeks until plasma HIV RNA levels are undetectable
- Every 2 months for the remainder of the pregnancy
One log decline in plasma viremia expected 1 month after initiation of therapy.
Complete viral suppression achieved within 12 to 24 weeks after initiation of therapy
Plasma HIV RNA viral level assessment at 36 weeks of gestation to decide mode of delivery
- Plasma HIV RNA VL >1,000 copies/mL = cesarean delivery
- Plasma HIV RNA VL <1,000 copies/mL = may have vaginal delivery if no obstetric contraindication
Repeat genotypic resistance testing in patients who report adherence but experience suboptimal viral suppression or viral rebound to detectable levels.
Monitor for common complications of ART during pregnancy (renal dysfunction when receiving tenofovir, or anemia due to zidovudine).

Ultrasound

Table 5-1 List of Anti-retrovirals Commonly Used in Pregnancy. ( List includes individual medications and co-formulations)

Drug (Abbreviated Name) Trade Name	Dosage Recommendation	Co-Formulations	PKs	Recommendations for Use in Pregnancy
NRTI
Lamivudine (3TC) Epivir	150 mg b.i.d. or 300 mg once daily	Combivir (AZT+3TC) 3TC 150 mg + ZDV 300 mg	PK not significantly altered. High placental transfer	Recommended dual-NRTI backbone in ART-naïve patients
Zidovudine (AZT, ZDV) Retrovir	300 mg b.i.d. or 200 mg t.i.d.	Combivir 1 tablet b.i.d.	PK not significantly altered. High placental transfer	Recommended dual-NRTI backbone in ART-naïve patients. Monitor for anemia
Abacavir (ABC) Ziagen	Ziagen 300 mg b.i.d. or 600 mg once daily	Epzicom (ABC+3TC) ABC 600 mg + 3TC 300 mg	PK not significantly altered. High placental transfer	Alternative NRTI for dual-NRTI backbone
Emtricitabine (FTC) Emtriva	Emtriva 200-mg capsule once daily or 240 mg (24 mL) oral solution once daily	Truvada (FTC+TDF) FTC 200 mg + TDF 300 mg. Atripla^a (EFV+FTC+TDF) 1 tablet at or before bedtime. Take on an empty stomach to reduce side effects.	PK slightly lower levels in third trimester. No clear need to increase dose. High placental transfer	Alternative NRTI for dual-NRTI backbone
Tenofovir Disoproxil Fumarate (TDF) Viread	Viread 300-mg tablet once daily	Truvada 1 tablet once daily. Atripla^a 1 tablet at or before bedtime	High placental transfer to fetus	Preferred NRTI in combination with 3TC or FTC in women with chronic HBV infection. Because of potential for renal toxicity, renal function should be monitored.
NNRTIs
Nevirapine (NVP) Viramune	200-mg tablets or 50-mg/5-mL oral suspension	PK not significantly altered. High placental transfer	Initiate in pregnant women with CD4 counts >250 cells/mm³ only if benefit clearly outweighs risk because of the increased risk of potentially life-threatening hepatotoxicity in women with high CD4 cell counts
Efavirenz^a (EFV) Sustiva	600 mg once daily at or before bedtime Take on an empty stomach to reduce side effects.	Atripla^a 1 tablet once daily at or before bedtime	No change in dose indicated. Moderate placental transfer to fetus	EFV should be avoided in the first trimester. Use after the first trimester can be considered if, after consideration of other alternatives, this is the only choice for a specific woman.
Etravirine (ETR) Intelence	200 mg b.i.d. Take following a meal		No PK studies in human pregnancy, placental transfer rate unknown	No experience in human pregnancy
Rilpivirine (RPV) Endurant	25 mg once daily with a meal.	Complera (RPV+TDF+FTC) RPV 25 mg + TDF 300 mg + FTC 200 mg	No PK studies in human pregnancy, placental transfer rate unknown	No experience in human pregnancy
PIs
Lopinavir + Ritonavir (LPV/r) Kaletra	Tablets: (LPV 200 mg + RTV 50 mg) or (LPV 100 mg + RTV 25 mg) standard dose is LPV/r 400mg/100mg b.i.d	Increase dose to LPV/r 600 mg/150 mg b.i.d. in second and third trimester	PK suggests dose should be increased to 600 mg/150 mg b.i.d. in second and third trimester. Low placental transfer	Recommended PI in ART-naïve patients. There is extensive experience with use in pregnancy.
Atazanavir (ATV) Reyataz (combined with low-dose ritonavir [RTV] boosting)	ATV 300 mg + RTV 100 mg once daily		PK suggests that standard dosing results in decreased plasma concentration compared with non-pregnant adults. However, for most pregnant women, dose adjustment of ATV is not needed. Low placental transfer to fetus	Alternative PI. ART-experienced pregnant women on either tenofovir or H2-receptor blocker (not both) should increase ATV dose to 400 mg (with ritonavir 100 mg).
Darunavir (DRV) Prezista (combined with low-dose RTV boosting)	(DRV 800 mg + RTV 100 mg) once daily. (DRV 600 mg + RTV 100 mg) b.i.d. if any DRV resistance mutations		No PK studies in human pregnancy. Minimal to low placental transfer to fetus	No data about the use of DRV in pregnancy but clinically there has been an increase in its use in pregnancy.
Integrase Inhibitors
Raltegravir (RAL) Isentress	400-mg tablets b.i.d.	With rifampin: 800 mg b.i.d.	Standard dose appears appropriate during pregnancy. Variable but high placental transfer to fetus	No experience in human pregnancy
^aAvoided in first trimester, and may be considered by some clinicians as a last resort later in pregnancy. But generally to be avoided.