# Presentation: 498328

## HIV Infection in Pregnancy: 2007 Update

- HIV Infection in Pregnancy: 2007 Update

- George J. Gilson, M.D.
- Alaska Native Medical Center

- Wrangell-St. Elias Range - 2004

## HIV Infection in Alaska: 2004

- Alaska has 1,002 total cases of HIV
- Alaska Natives accounted for 23% (n=228)
- Women accounted for 18% (n=175)
- AN/AI women accounted for 32% of these (n=56)
- Perinatal acquired cases 2% (n=7)

## HIV in Pregnancy: Case 1

- Nellie Benally is a 22 y/o G3P0 at 11 weeks gestation whose routine prenatal HIV test (both EIA and WB) returns (+). She had a former partner who was an IVDU.
- What are the your next steps?

## HIV in Pregnancy: Per-contact Risk of Infection

- _Exposure_				_Risk_
- Receptive vaginal			2-8/1000
- Insertive vaginal			1-3/1000
- Needle sharing			3-6/1000
- Occupational needle stick	1/300

## HIV Screening in Pregnancy Issues

- “opt-in” vs. “opt-out” (informed refusal)
- removes the stigma
- part of routine prenatal labs
- 53% vs. 89% choose testing
- current approach recommended by the CDC, ACOG, and AAP

## HIV Screening in Pregnancy Issues

- Repeat testing in the 3rd trimester? Who?
- Hx STD
- IVDU
- Multiple partners
- Opportunistic infection
- Previously declined testing

## HIV Screening in Pregnancy Issues

- Rapid screening in labor?
- Whole blood, done in L&D
- Results in 20-40 minutes
- OraQuick probably the best (CLIA-waived)
- Sensitivity, specificity, PPV approach 100%
- Initiate prophylaxis and order Western blot to confirm

## HIV Screening in Pregnancy:ANMC Experience	

- Use of “out out” strategy
- 96% of women had a prenatal HIV screen done at the first visit
- 4% declined at the initial visit
- 2% eventually agreed to screening later
- 3% had no screen in labor (transfers in)

## HIV Screening in Pregnancy Issues

- What about “indeterminate” results?
- (+) EIA but WB (-): not infected
- (+) EIA but WB “indeterminate” (<3 bands)
- relatively common in multiparous women
- risk factors? (low prevalence means more false positives...)
- repeat the WB in 3 months
- get a viral load

## HIV in Pregnancy: Other TestsViral Load

- -  viral load is the key to preventing perinatal transmission
- -  goal is to reduce viral load to undetectable (<1,000 copies/mL)
- -  repeat q 2-3 mos, or at least q trimester
- -  2 assay types:
- 	-b-DNA (HIV-1 RNA)
- 	-RT-PCR

## HIV in Pregnancy: Other TestsCD4+ Count

- measure of host immune response
- if <500/mL, repeat every trimester
- if <200/mL, begin PCP prophylaxis
- CD4+ = wbc x %lymphs x %CD4
- eg.  = 10,000 x .30 x .30 = 900

## HIV in Pregnancy: Other TestsBaseline Labs

- CBC (anemia with ZDU)
- LFTs (mitochondrial disease with NRTI, elevated ALT w/ NNRTI and PI)
- amylase (pancreatitis with NRTI)
- early 1-hr OGT (GDM with PI)
- creatinine
- Hep C, CMV, toxo

## Bridal Veil Falls

-          2004

## HIV in Pregnancy: Treatment

- The goal in pregnancy is to reduce viral load to undetectable to minimize perinatal transmission.
- Is the woman willing and able to adhere to the regimen?
- What are the risks and benefits?

## HIV in Pregnancy: Therapy“The Milestone Study”

- _ACTG 076 (1994)_
- Zidovudine (ZDU, formerly AZT) PO prenatally from 14-34 wks to term: 100 mg 5x/d
- ZDU in labor IV: 2 mg/kg load, 1 mg/kg/h maintenance
- ZDU to neonate: 2mg/kg/q6h x 6 wks
- Reduced vertical transmission from 26% to 8%

## HIV in Pregnancy: Therapy

- Any pregnancy regimen should include ZDU, however....
- Combination highly-active anti-retroviral therapy (HAART) is standard in non-pg
- Safety of HAART in pregnancy is reassuring
- No evidence to date that resistance is a major problem for the mother after the pregnancy

## HIV in Pregnancy: Therapy

- Pick the regimen that will be easiest to adhere to and have the fewest side effects
- “2 pills twice a day every day”
- ZDU 200 mg/lamivudine 150 mg(Combivir) + nelfinavir 1250 mg PO bid
-  - Side effects generally mild and treatable: anemia, headache, nausea, diarrhea

## HIV in Pregnancy: Therapy

- Check viral load, CD4+, LFTs, CBC q trim
- Consider change of therapy if viral load still detectable in 3-6 months
- Is she taking her meds??
- Resistance testing usually not indicated during pregnancy (consult)
- perinatal transmission of resistant virus rare
- no improvement in perinatal outcomes

## HIV in Pregnancy: Case 2

- Adelina Low Dog is a 29 y/o G3P2 at 16 wks who is known to be HIV infected and is on triple therapy (ZDU, lamivudine, ritonavir) x 3 yrs. CD4+=373, HIV b-DNA = 490 copies/mL. Now that she is pregnant, is it safe to continue her current meds?

## HIV in Pregnancy: Therapy

- Are there any ART drugs contraindicated during pregnancy?
- Most HAART drugs have FDA pregnancy classification C (a few B), however....
- Efavirenz, delaviridine, zalcitabine, and hydroxyurea are teratogenic in animals
- Enfuvirtide, fosamprenavir, atazanavir, tenofovir have insufficient data in pregnancy

## HIV in Pregnancy: Therapy Issues

- Is HAART associated with an increased incidence of preterm birth/LBW?
- Is combo HAART superior to ZDU alone?
- If the patient has ZDU resistance, should it still be given during pregnancy?
- Is lactic acidosis and fatty liver increased in pregnant patients?

- Ship Lake 2004

## HIV in Pregnancy: Case 3

- Nora Koyukuk is a 32 y/o G5P4 w/o PNC who presents in false labor at 37 wks and has an HIV test drawn. When she returns the following week she is in active labor (cx 3 cm/75%/-1 sta, BOW-I) and the test is found to be positive. How should you manage?

## HIV in Pregnancy: Is Cesarean Delivery Necessary?

- _French Perinatal Cohort -1998 (n=2819)_
- _HIV(+) taking ZDU (n=902)_
- Emergent cesarean	11.4% transmission
- Vaginal delivery		6.6% transmission
- Elective cesarean		0.8% transmission

## HIV in Pregnancy: Is Cesarean necessary?

- _French Perinatal Cohort (1998) (n=2819)_
- _HIV(+)/ __*not*__ taking ZDU (n=1917)_
- Emergent cesarean	15.6% transmission
- Vaginal delivery		17.5% transmission
- Elective cesarean		17.2% transmission

## HIV in Pregnancy:Is Cesarean Necessary?

- _International Perinatal HIV Group (1999)_
- Meta-analysis – 15 studies (n=8533)
- ZDU alone			  7% transmission
- Cesarean alone	     	10% transmission
- ZDU + cesarean		  2% transmission

## HIV in Pregnancy:Is Cesarean Necessary?

- _PACTG-367 – (2004) (n=347 pairs)_
- Unknown viral load	11.6% transmission
- >10,000 copies		   4.6% transmission
- <10,000 copies		   2.3% transmission
- Undetectable		   0.9% transmission

## HIV in Pregnancy:Is Cesarean Necessary?

- Elective cesarean delivery decreases perinatal HIV transmission
- Women on HAART may not derive further benefit from cesarean delivery
-  Women with undetectable viral loads may not derive benefit from cesarean delivery

## HIV in Pregnancy: Is Cesarean Necessary?

- Women with viral loads of <1,000 copies should be offered vaginal delivery
- Women with >1,000 copies should be offered elective cesarean at 38 weeks
- Women’s autonomy should always be respected, especially in this situation where the data are insufficient

## Parking violation????

## HIV in Pregnancy: How about ruptured membranes?

- Probability of transmission

- Duration of ruptured membranes

- N Engl J Med 1996;334;1617-23. Copyright Massuchusetts Medical Society

## HIV in Pregnancy: Management of Labor

- All patients should get IV ZDU per the _ACTG 076_ protocol:
- ZDU 2 mg/kg IV load  1 mg/kg/hr IV maintenance throughout labor
- No AROM, no IUM, no scalp electrodes, no forceps/VE, no episiotomy
- Augment labor if SROM

## HIV in Pregnancy: Case 4

- Sophie Aquino is a 34 y/o G8P7 who has had no PNC. She presents in active labor and is found to be completely dilated. She precipitously delivers a healthy newborn. Her screening lab work reveals she is HIV(+). How should this infant be managed?

## HIV and BreastfeedingAfrican Data

- Overall risk of neonatal transmission is 14% over 2 years of nursing
- More diarrhea associated deaths however
- Breast feeding mothers fare less well (11% vs. 4% death) at 2 years post delivery
- ZDU or nevirapine po may decrease transmission 37-49%
- Breast feeding is contraindicated in the US

## There is no duty we so much underrate as the duty of being happy.“            Robert Louis Stevenson

- There is no duty we so much underrate as the duty of being happy.“            Robert Louis Stevenson

## HIV: Management of the Newborn

- Infants should receive po ZDU according to the _ACTG 076_ protocol:
- ZDU 2 mg/kg/dose q6h x6 wks beginning 6-12h after birth
- CBC, LFTs, CD4+, WB, viral load
- Viral load at birth, 6 wks, 6 mos, 18 mos
- PCP prophylaxis at 6 wks (SMX/TMP)

## HIV: Postpartum Care

- Women with viral loads >55,000 copies and/or CD4+ <350/mm should be offered long-term HAART (keep it simple!)
- Women with low level viral loads should be followed q 3-6 mos for progression
- No breast feeding
- Contraceptive issues

## HIV in PregnancyReferences

-  - PHS Task Force Recommendations
-  - _[http://AIDSinfo.nih.gov](http://aidsinfo.nih.gov/)_
-  - _[www.hivatis.org](http://www.hivatis.org/)_
-  - _[http://www.apregistry.com](http://www.apregistry.com/)_

## The End...

**The End...**