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Ovid: Oxford Handbook of Genitourinary Medicine, HIV, and Aids

Editors: Pattman, Richard; Snow, Michael; Handy, Pauline; Sankar, K. Nathan; Elawad, Babiker Title: Oxford Handbook of Genitourinary Medicine, HIV, and Aids, 1st Edition Copyright ©2005 Oxford University Press > Table of Contents > HIV/AIDS > Chapter 54 – HIV: pregnancy Chapter 54 HIV: pregnancy P.536
Preconception Advise HIV discordant couples wishing to conceive on maximizing the chance of conception while minimizing the risk of sexual transmission. ♀ HIV +ve/♂ HIV –ve Advise on how to perform artificial insemination at the time of ovulation, using quills, syringes, and Gallipots. ♂ HIV +ve/♂ HIV –ve

  • Transmission risk ~1:500 per unprotected sexual act, therefore after discussion of risk advise unprotected sexual intercourse around the time of ovulation.
  • Sperm washing, spermatozoa separated from surrounding HIV-infected seminal plasma by a sperm swim-up technique, is available in a number of centres in the UK. To date, there have been no cases of seroconversion in ♀ inseminated with washed sperm.
  • If ♂ has low sperm count, intracytoplasmic sperm injection following sperm washing may be offered.

In vitro fertilization Now considered ethically acceptable for subfertility because of vertical transmission rates of <2% and ↑ life expectancy for parents taking HAART. The effectiveness of pre-conceptual folic acid for those requiring such prophylaxis is unknown although a higher, 5mg dose is recommended. Contraception (see p. 332.). Mother to child (vertical) HIV transmission without intervention Vertical transmission rates vary from 15 to 20% in non-breastfeeding European ♀ to 25–40% in African ♀ who breastfeed. Although transmission is associated with advanced HIV disease and low antenatal CD4 count a high maternal VL is the strongest individual predictor. In ♀ who do not breastfeed >80% of vertical transmission occurs late in the 3rd trimester (from 36 weeks), during labour and at delivery, with <2% during the 1st and 2nd trimesters. The main obstetric risk factors are vaginal delivery, duration of membrane rupture, chorioamnionitis, and preterm delivery. It is estimated that breastfeeding ↑ the mother to child transmission rate by 14% for ♀ infected with HIV before birth and by 30% in those infected postnatally. In ♀ without advanced disease N. American and European studies suggest no ↑ risk of accelerated immunosuppression during pregnancy. CD4 counts may fall but return to pre-pregnancy levels after delivery. P.537
Frequently asked questions Can I get pregnant? It is possible for an HIV +ve ♀ to have a baby. The risk of vertical transmission is 15–40% but this is ↓ to <2% with retroviral treatment, caesarean section (if viral suppression inadequate) and avoidance of breastfeeding. Also the parents’ life expectancy is ↑ with treatment if it is required. Artificial insemination techniques avoid the risk of transmission to an HIV –ve ♂ partner and sperm washing ↓ the risk of a positive ♂ infecting a ♀. Can I have a vaginal delivery? It is generally advisable to have an elective caesarean section as it ↓ the risk of vertical transmission by 50%. However, if there is good viral suppression vaginal delivery may be acceptable. Can I breast feed? No. There is a high risk of mother to child transmission with breastfeeding. P.538
Vertical HIV transmission with intervention Transmission rate has been reduced to <2% by:

  • anti-retroviral therapy, given antenatally and intrapartum to the mother and to the neonate for the first 4–6 weeks of life
  • delivery by elective caesarean section
  • avoidance of breastfeeding.

Management ▶ Guidance on the management of HIV infection changes rapidly with new evidence. It is therefore important to consult contemporary guidelines (see useful resources). Identification Routine antenatal HIV antibody testing should be advised and offered to all pregnant ♀ in early pregnancy (usually at booking). Midwives must be able to provide information on the benefits of early diagnosis ensuring that an expert sees newly diagnosed cases promptly. Management during pregnancy should be multidisciplinary involving an obstetrician, HIV physician, midwife, paediatrician, and appropriate others (e.g. social worker, psychologist). Partner notification should be managed with the ♀’s co-operation and support. However, in the absence of this, the ♀’s HIV status may be disclosed to an at-risk sexual contact (for his protection) although the ♀ must be informed and the clinician able to justify this action. Otherwise assurances should be given regarding confidentiality especially relating to friends and relatives accompanying the ♀ who may be unaware of her HIV diagnosis. Advice should be given about avoiding unprotected sexual intercourse both for the benefit of partner(s) and the safety of the ♀. Assessment and screening Repeat HIV antibody test, to confirm and assess as for any newly diagnosed case (see p. 370) with close monitoring of CD4 counts and plasma viral loads (VLs). HIV infection is associated with presence of other STIs that may ↑ genital HIV VL potentially increasing the risk of vertical transmission. Screening should include:

  • serological testing for syphilis, hepatitis B and C viruses (if not already done at booking)
  • specimens for Chlamydia trachomatis, Neisseria gonorrhoeae,Trichomonas vaginalis, and bacterial vaginosis.

Anti-retroviral treatment ▶ Advised for all ♀ during pregnancy and at delivery. The AIDS Clinical Trials Group protocol 076 (1994) demonstrated that zidovudine monotherapy, initiated between 14 and 34 weeks of pregnancy, P.539
intravenously during delivery and to infants for 6 weeks, ↓ risk of HIV-1 infection if not breastfeeding from 25.0% to 7.6%. In the UK zidovudine is currently the only antiretroviral drug specifically indicated for use during pregnancy (excluding 1st trimester) but monotherapy does not fully suppress plasma viraemia, leading to ↑ risk of viral resistance. Therefore HAART, involving 3 or more drug combinations should be used if the mother requires it for her own health. It should be considered if the CD4 count falls below 350cells/µL but may be deferred, especially with a low VL (<10,000copies/mL). Its introduction before the CD4 count falls <200cells/µL is important as opportunistic infections develop more commonly. Prophylaxis against Pneumocystis jiroveci (carinii) should be considered for those presenting with a CD4 count <200cells/µL. 1st line prophylaxis is co-trimoxazole, a folate antagonist, therefore potential benefits have to be balanced with the risks of fetal neural tube defects. If used in early pregnancy folic acid supplements should be provided and ultrasound scanning arranged after the 1st trimester. P.540
To prevent vertical transmission only (♀ does not requiring HIV treatment for own health) UK (RCOG) guidelines recommend starting treatment between 28 and 32 weeks of gestation (may be earlier if multiple pregnancy or history of preterm labour), US (CDC) guidelines from 14 to 34 weeks. Options are:

  • short-term anti-retroviral therapy (START), especially with a high VL (>10,000copies/mL).
    • During pregnancy: HAART regimen, if possible containing zidovudine, which may be stopped shortly after pregnancy providing that the maternal VL is <50copies/mL.
    • Pre-delivery: intravenous zidovudine infusion, 2mg/kg for 1st hour reducing to 1mg/kg/hour until delivery. If stavudine is part of the HAART regimen it should be stopped as it competes with zidovudine for the same phosphorylation pathway
    • Delivery: requirement for caesarean section uncertain if VL<50copies/mL.
    • Neonate: oral zidovudine syrup, 2mg/kg four times a day for 6 weeks.
  • zidovudine monotherapy
    • During pregnancy: 300mg twice daily or 200mg three times a day by mouth, stopping immediately after delivery
    • Pre-delivery: start intravenous zidovudine infusion, 2mg/kg for 1st hour reducing to 1mg/kg/hour until delivery
    • Delivery: caesarean section
    • Neonate: oral zidovudine syrup, 2mg/kg four times a day for 6 weeks.

Consensus appears to be moving away from monotherapy as combination treatment is more likely to suppress VLs to undetectable levels with a ↓ risk of viral resistance. However, its use must be balanced against the risks to mother and fetus of exposure to multiple potentially toxic drugs. Evidence suggests that pre-eclampsia is more common among pregnant treated ♀ with HAART, but there is no apparent ↑ rate of premature delivery, ↓ birth weight, ↓ Apgar scores, or stillbirths with such regimens with or without protease inhibitors. Treatment in advanced HIV infection Ideally resistance testing should be performed before commencing HAART, if possible deferring its introduction until the end of the 1st trimester or beginning of the 2nd. It should be continued after delivery. A zidovudine containing regimen is recommended unless there is resistance or other contraindication (extensive safety data in pregnancy). Zidovudine should be given intrapartum, even if not used as part of the maternal regimen, by infusion, until the cord is clamped. Treatment as described above should be given to the neonate for 6 weeks. Women conceiving while taking HAART Continue regimen if effective viral suppression. If failing, consider changing therapy after 1st trimester following resistance testing. P.541
P.542
Women presenting in late pregnancy or during labour If immunological and virological assessment is not possible, HAART, including zidovudine (intravenously intrapartum), should be started. Continue HAART intrapartum and postpartum until the results of the CD4 count and VL are known. Delivery should be by caesarean section with consideration given to its timing to allow peak fetal concentrations. If this is not available a single 200mg oral dose of nevirapine can be given during labour and the neonate treated with nevirapine, 2mg/kg 48 hours post-delivery. Nevirapine monotherapy may lead to non-nucleoside reverse transcriptase inhibitor resistant mutations which could compromise future treatment options for the ♀as well as ↑ risk of further transmission of resistant virus. Symbol

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Options in countries with limited resources

  • Zidovudine/lamivudine combination: from 36 weeks of gestation, intrapartum and for 1 week postpartum—50% ↓ in vertical transmission for African breastfeeding ♀.
  • Nevirapine (long half-life): single 200mg dose at onset of labour and 2mg/kg single dose to the neonate 48 hours post-delivery. Relative efficacy at 14–16 weeks—47%. All ♀ who receive antiretroviral therapy in pregnancy should be registered prospectively with the Anti-retroviral Pregnancy Registry, which in Europe is managed by GlaxoSmithKline (http://www.uk.gsk.com).

Obstetric arrangements Elective caesarean section before labour or rupture of membranes Overall provides 50% ↓ in vertical transmission persisting when anti-retroviral treatment used. Effective even with low VL (1000copies/mL) but additional benefit uncertain in those taking HAART if VL <50copies/mL. US (ACOG) guidelines recommend elective caesarean section if maternal VL near delivery is >1000copies/mL. It should be timed to take place after 38 weeks of gestation. ‘Bloodless’ technique (using a staple gun) may further reduce transmission rates. Prophylactic antibiotics are recommended. A zidovudine infusion should be started 4 hours before beginning the caesarean section and continued until the umbilical cord has been clamped. Maternal VL should be checked at delivery. The cord should be clamped as soon as possible after delivery and the baby bathed immediately after birth. Vaginal delivery If a woman chooses a vaginal delivery:

  • membranes should be left intact for as long as possible
  • fetal scalp electrodes and fetal blood sampling should be avoided
  • emergency caesarean section may be required for other obstetric reasons including prolonged rupture of membranes (in pre-HAART era transmission rate doubled after 4 hours).

The neonate All infants born to ♀ who are HIV +ve should be treated with anti-retroviral therapy from birth. Unless the mother started anti-retroviral therapy late in pregnancy (within 4 weeks of delivery) treatment of the infant may be discontinued after 4–6 weeks. Zidovudine monotherapy should be used if the infant’s mother received zidovudine antenatally or intrapartum, either as monotherapy or in HAART regimen. Consider HAART for neonates of mothers starting antiretroviral therapy late in pregnancy, with a high VL at delivery or a complicated delivery. Preterm or sick infants may not tolerate oral therapy and zidovudine is the only anti-retroviral drug available as an intravenous preparation. Maternal antibodies crossing the placenta are detectable in most neonates of mother who are HIV-positive. Therefore nucleic acid amplification, by an ultrasensitive polymerase chain reaction technique, is used for the early diagnosis of infant infection. Typically tests are carried out at birth, then at 3 weeks, 6 weeks, and six months. At 6 months this test will detect >99% of infected babies if not breastfed. Final confirmation is a negative HIV antibody test at 18 months of age, following decay of maternal antibodies. Infant feeding All HIV positive mothers should be advised to avoid breastfeeding.Mixing breast with artificial feeding appears to ↑ risk of viral transmission compared with breastfeeding alone (African data). P.543
Anti-retroviral drugs used in pregnancy with usual doses Nucleoside reverse transcriptase inhibitors (NRTIs) Recommended

  • Zidovudine (300mg twice daily): preferred NRTI in HAART that usually includes 2 NRTIs with either a NNRTI or one or more PIs.
  • Lamivudine (150mg twice daily): in combination with zidovudine recommended NRTI backbone for pregnant ♀.

Alternative

  • Didanosine (400mg either single daily dose or 200mg twice daily):only use with stavudine if no other options. Lactic acidosis, including fatalities, has been reported with this combination.
  • Stavudine (40mg twice daily): only use with didanosine if no other options (see above). Avoid concurrent use with zidovudine due to potential antagonism.
  • Abacavir (300mg twice daily): in non-pregnant hypersensitivity 5–8%.
  • Emtricitabine (200mg daily): another NRTI for dual nucleoside background though no data in pregnancy.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Recommended

  • Nevirapine (200mg daily for 1st 14 days then 200mg twice daily): caution in combination therapy if CD4 counts >250cells/µL when initiating treatment in ♀. ↑ risk of potentially fatal liver toxicity, often associated with a rash. (Unclear if further ↑ risk with pregnancy.)

Avoid

  • Efavirenz: reports of neural tube defects in infants when used in 1st trimester.

Protease inhibitors (PIs) Recommended

  • Nelfinavir (1.25g) twice daily: preferred PI in pregnancy.
  • Saquinavir tablets (1g) boosted with ritonavir (100mg) twice daily: considered as a preferred PI for combination treatment.

Alternative

  • Indinavir (800mg) boosted with ritonavir (100mg) twice daily: although indinavir produces viral suppression blood levels are lower during pregnancy. Boosting with ritonavir is probably required.
  • Lopinavir (400mg) + ritonavir (100mg) twice daily: early studies suggest ↑ dose may be required during pregnancy.

Monitoring in pregnancy Electrolytes and liver function tests should be performed every 2 weeks during the 3rd trimester in view of the potential risk of lactic acidosis and hepatic steatosis when using nucleoside reverse transcript- ase inhibitors.

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