Christopher J. Hoffmann, M.D., M.P.H.
- HIV transmission risk to infant is 15-30% during labor & delivery and 15% during breast feeding. Rate of transmission during normal gestation is very low.
- Uncontrolled HIV decreases fertility (by approx. 30%); correlates with VLand disease state
- Uncontrolled HIV worsens pregnancy outcomes (increased still birth, low birth weight, intrauterine growth retardation, chorioamnionitis) and increases maternal mortality (5-fold increase).
- Control of HIV restores fertility (unexpected pregnancy occurs on average of 1 year after ART initiation)
- HIV transmission from mother to child occurs in 15-30% of live births and 15% of breast-fed infants. Risk of HIV during pregnancy, delivery, and breastfeeding is approximately 40% without any interventions for prevention of mother to child transmission (PMTCT).
- Predictors of transmission: acute HIV infection during pregnancy, higher viral load, genital ulcer disease, active HSV
- Pregnancy does not increase HIV progression, risk for OIs, or HIV-related survival.
- Pregnancy-related hemodilution may cause apparent decrease in CD4 count (not CD4 %), esp. in 3rd trimester.
- All pregnant women must be screened for HIV during 1st and 3rd trimesters and consider post-partum to identify new HIV during breast feeding. Also should receive standard antenatal syphilis screening, symptomatic STD screening, supplementation of folate, iron, vitamin A, multivitamins and trace minerals.
- HIV+ women need HIV care and PMTCT services
- Use of PMTCT can decrease rate of transmission during labor/delivery and breastfeeding to 1-5% (from 40%).
EFV is a class D agent; use during 1st trimester may increase risk of neural tube defects. Risk is likely to be low based on US birth registry and African experience. Because neural tube develops during 1st trimester, use after this period is probably safe.
- Initiate HAART with NVP (if CD4 <250, if >250 high risk of hepatotoxicity with NVP) instead of EFV if pregnancy identified in 1st trimester. If pt already on EFV, switch to NVP, even if CD4 >250. Start with full dose NVP 200 mg twice-daily when switching from EFV (no induction dose needed.)
- AZT & 3TC have demonstrated safety. ABC & TDF also appear safe..
LPV/r: decreased serum concentrations during 3rd trimester, of unclear clinical significance in treatment-naive patients. Consider increasing to 3 tabs (600/150 mg) twice-daily during 3rd trimester, especially for PI experienced patients.
d4T + ddI: Do not use because of increased risk of pancreatitis and lactic acidosis.
- ART: Continue ART if on ART. If not on ART, defer initiation until 2nd trimester if mother meets WHO initiation criteria for pregnancy (WHO stage IV; WHO stage III & CD4 <350; CD4<200; Consider if CD4 <350). Recommended regimen for pregnancy: NVP, AZT, 3TC
- No ART, HIV identified early in pregnancy: AZT (300 mg PO twice-daily) starting at 28 wks + AZT 600 mg at onset of labor + single dose (sd)-NVP 200 mg at onset of labor. Post-partum: AZT 300 mg twice-daily + 3TC 150 mg twice-daily x 7-14 days (can also use TDF 300 mg + 3TC 300 mg once-daily x 7-14 days)
- No ART during pregnancy: sd-NVP 200 mg at onset of labor followed by AZT 300 mg twice-daily + 3TC 150 mg twice-daily for 7-14 days
- HAART for mother: fully suppressive HAART prevents transmission via breast milk to the infant
- Post-partum: Infant regimen is NVP 2 mg/kg (or 6 mg) immediately after birth + AZT 4 mg/kg twice daily x 7-42 days.
- If breast feeding: consider NVP (2 mg/kg daily or 5 mg daily) x 6-24 wks (not yet part of WHO guidelines).
- If breast feeding: Exclusive breast feeding may reduce transmission vs. mixed feeding (mixed evidence). High risk of transmission with either exclusive or mixed if no maternal HAART or infant ART prophylaxis.
- WHO recommends exclusive replacement feeding (formula) when acceptable, feasible, affordable, sustainable, and safe. However, replacement feeding not recommended for public health approach based on Botswana study in which exclusive replacement feeding increased diarrheal illness and mortality.
- HIV-negative mothers can become infected during post-natal period. HIV testing and counseling is important if mother is breast feeding.
- Following sd-NVP, resistance to NVP detectable among 20-70% of mothers and 30-80% of infected infants.
- Resistance can be reduced if mother takes AZT+3TC (or TDF+FTC) 1-2 weeks post-partum or if full HAART used during the antenatal period and continued post-partum
- When NVP resistance detectable following sd-NVP, poorer response to NVP or EFV-containing ART if ART started <6 months after receiving sd-NVP. Improved responses with longer intervals between sd-NVP and ART, but durability of response unknown.
- For mothers, ART containing NVP or EFV MUST be delayed >6 months after a mother has received sd-NVP.
- For infants, impact of detectable NVP resistance unclear, but probably compromises NVP or EFV-based ART.
- Infants at risk for MTCT benefit from cotrimoxazole therapy until they are proven HIV-uninfected or CD4 % >25%.
- Consider starting cotrimoxazole 4-6 wks post-partum in infant. Dose: <6 months, SMX/TMP 100/20mg daily; 6 months - 5 yrs, SMX/TMP 200/40 mg daily.
- Malaria risk increased 3-fold by HIV during pregnancy. In addition, HIV reduces effectiveness of WHO recommended 2-dose intermittent preventive treatment during pregnancy with sulfadoxine + pyrimethamine.
- A more effective regimen for preventing malaria parasitemia during pregnancy is monthly sulfadoxine 1500 mg + pyrimethamine 75 mg
Cotrimoxazole also effective for preventing malaria, but not as well studied in pregnancy as sulfadoxine-pyrimethamine.
- Maternal antibodies can remain detectable in infants >1 year post-partum.
- Antibody testing is only interpretable >15-18 mos post-partum. Earlier testing for infection requires nucleic acid testing (PCR to detect HIV RNA or DNA).
- If only antibody tests available, testing should be delayed until 18 mos of age.
- Clinical Dx not sensitive for HIV, as many HIV+ infants remain healthy for 1st year of life. (IMCI clinical Dx guidelines: any 3 of the following: recurrent pneumonia, oral thrush, present or past ear discharge, persistent diarrhea, very low weight, enlarged lymph nodes, parotid enlargement).
- Major current limitation with PMTCT is delivery of services. Current factors limiting delivery are lack of participation by mothers due to stigma of HIV testing and social pressures, availability of testing services, home birthing, and failure to ingest supplied sd-NVP tablet.