Pregnancy and HIV

Treatment of Pregnant Women Living with HIV or Women Considering Pregnancy

Treatment Scenarios

Pregnant Women / Women Who Wish to Conceive

 

1. Women planning to be pregnant or becoming pregnant while already on ART

Maintain ART, unless taking not recommended drugs (see Tables 1 and 2)

2. Women becoming pregnant while treatment-naïve

Starting ART as soon as possible is highly recommended (See Table 3)
3. Women whose follow-up starts late in the second or in the third trimester Start ART immediately (see Table 2) and consider RAL or DTG as the preferred choice to obtain rapid HIV-VL decline and to ensure the HIV-VL is undetectable by the time of delivery
4. Women whose HIV-VL is not undetectable at third trimester Perform resistance testing and consider changing to or adding INSTI (RAL or DTG) if not on this class to obtain rapid HIV-VL decline
5. Women whose HIV-VL is > 50 copies/mL at week 34-36 of pregnancy Elective cesarean section to be planned at week 38, see labour and breastfeeding
6. Women diagnosed with HIV in labour See labour and breastfeeding

Antiretroviral Drugs

Table 1: ARV Drugs Not Recommended in Women Who Wish to Conceive

DRUG

 Reason

 INSTI

 

 DTG

Higher risk of neural tube defects if used preconception. Should be switched to another drug

 

Table 2: ARV Drugs Not Recommended in Women Who Become Pregnant While on ART

DRUG

 Reason

NRTI

 

TAF

Insufficient data about safety and efficacy in pregnancy

INSTI  
RAL qd  Insufficient data about safety and efficacy in pregnancy
BIC  Insufficient data about safety and efficacy in pregnancy
DTG  Higher risk of neural tube defects if used periconception
EVG/c  Lower levels during pregnancy
NNRTI  
DOR  Insufficient data about safety and efficacy in pregnancy
PI  
ATV/c  Lower levels during 2nd and 3rd trimester
DRV/c  Lower levels during 2nd and 3rd trimester
 OTHER  
 COBI Low levels during 2nd and 3rd trimester of pregnancy, subtherapeutic levels of boosted drug should be expected

ARV Regimen

Table 3: Antiretroviral Regimen for ART-naïve Pregnant Women

Pregnant women should be monitored monthly or bimonthly (depending on prior adherence and length of prior virological suppression) and as close as possible to the predicted delivery date. HIV-VL should be tested every two months of pregnancy and including 36 weeks of gestation.

 Regimen Main Requirements Footnotes (Additional Guidance)
Recommended regimens
2 NRTIs + INSTI (PREFERRED)
ABC/3TC + DTG
ABC/3TC/DTG
Initiate after 8 weeks of pregnancy
HLA-B*57:01 negative
HBsAg negative
I     (ABC: HLA-B*57:01, may delay starting ART)
II   (DTG: neural tube defects risk during periconception)
TDF/FTC or TDF/3TC + DTG Initiate after 8 weeks of pregnancy III  (Tenofovir salts)
II   (DTG: neural tube defects risk during periconception)
TDF/FTC or TDF/3TC + RAL 400 mg bid   III (Tenofovir salts)
IV  (RAL in pregnancy, bid dosing)
2 NRTIs + PI/r
TDF/FTC or TDF/3TC + DRV/r 600 mg/100 mg bid With food III  (Tenofovir salts)
V   (DRV dosing)
VI  (COBI boosting)
Alternative regimens
2 NRTIs + INSTI
ABC/3TC + RAL 400 mg bid HBsAg negative
HLA-B*57:01 negative
I   (ABC: HLA-B*57:01, may delay starting ART)
IV (RAL in pregnancy, bid dosing)
2 NRTIs + NNRTI
ABC/3TC + EFV HLA-B*57:01 negative
HBsAg negative
HIV-VL < 100,000 copies/mL
At bed time or 2 hours before dinner
I    (ABC: HLA-B*57:01, may delay starting ART)
VII (EFV HIV-2 & group O)
TDF/FTC or TDF/3TC + EFV
TDF/FTC/EFV
At bed time or 2 hours before dinner III (Tenofovir salts)
VII (EFV HIV-2 & group O)
TDF/FTC or TDF/3TC + RPV
TDF/FTC/RPV
CD4 count > 200 cells/μL
HIV-VL <100,000 copies/mL
Not on proton pump inhibitor
With food
II    (Tenofovir salts)
VIII (RPV exposure during 2nd and 3rd trimester, HIV-2)
IX    (Interactions)
2 NRTIs + PI/r
ABC/3TC + ATV/r HLA-B*57:01 negative
HBsAg negative
HIV-VL < 100,000 copies/mL
Not on proton pump inhibitor
H2 blockers timing recommen-ded
With food
     (ABC: HLA-B*57:01, may delay starting ART)
VI    (COBI boosting)
IX    (Interactions)
X     (Maternal hyperbilirubinemia)
TDF/FTC or TDF/3TC + ATV/r Not on proton pump inhibitor
H2 blockers timing recommen-ded
With food
VI    (COBI boosting)
IX    (Interactions)
    (Maternal hyperbilirubinemia)
ABC/3TC + DRV/r 600 mg/100mg bid HLA-B*57:01 negative and
HBsAg negative
With food
     (ABC: HLA-B*57:01, may delay starting ART)
V     (DRV dosing)
VI    (COBI boosting)
Other drugs not recommended as initial therapy for PLWH but with evidence of safety during pregnancy
AZT   XI    (access)
XII   (toxicity)
LPV/r Dose increase recommended in third trimester of pregnancy XI    (access)
XIII  (toxicity)

Additional Guidance:

  1. ABC contraindicated if HLA-B*57:01 positive. Even if HLA-B*57:01 negative, counselling on HSR risk still mandatory. If testing for HLA-B*57:01 results in delay of ART initiation, consider other recommended backbone
  2. Data from the Tsepamo observational cohort showed neural tube defects occurred in 3 per 1000 deliveries among women on DTG from conception, a small but significant increase compared with all other antiretroviral exposures [16]
  3. Some generic forms of TDF use phosphate, maleate, and succinate salts instead of fumerate. They may be used interchangeably. In certain countries, TDF is labelled as 245 mg rather than 300 mg to reflect the amount of the prodrug (tenofovir disoproxil) rather than the fumarate salt (tenofovir disoproxil fumarate)
  4. There were no reports of neural tube defects among 1991 prospective reports of RAL exposure in pregnancy, 456 of which were in the periconception period. No data on RAL 1200 mg qd: not recommended
  5. DRV/r 800/100 mg qd not recommended during pregnancy due to decreased levels. DRV/c is not recommended during pregnancy due to significant lower exposures of DRV and COBI in the second and third trimester of pregnancy
  6. Boosting with COBI is not recommended after the second trimester of pregnancy (insufficient drug levels)
  7. EFV not active against HIV-2 and HIV-1 group O strains
  8. Lower RPV exposure during second and third trimesters; Consider monitoring VL more frequently. RPV is not active against HIV-2
  9. Pregnant women are often prescribed anti-H2 or proton pump inhibitors for nausea. Careful review of concomitant medicines at each visit and providing pregnant women with information on potential interactions is recommended
  10. ATV/r may produce maternal hyperbilirubinemia, no evidence for neonatal hyperbilirubinemia
  11. In countries with limited access to drugs listed in recommended and alternative regimens, treatment with 2 NRTIs + LPV/r or including AZT as part of the NRTI backbone are acceptable choices for pregnant women
  12. AZT may cause maternal anaemia, consider monitoring for haematological toxicity
  13. LPV/r has higher toxicity then other PIs (nausea)

Labour

Scenarios:

1) Women whose HIV-VL is > 50 copies/mL at week 34-36:

  • Elective cesarean section to be planned at week 38
  • iv ZDV: During labor and delivery: 2 mg/kg loading dose followed by continuous iv infusion of 1 mg/kg/hour until delivery
    • Scheduled cesarean delivery: start iv ZDV 3 hours before surgery
    • Unscheduled cesarean delivery: consider administering loading dose then proceed to delivery

2) Women diagnosed with HIV during labour:

  • If possible, perform caesarean section
  • iv ZDV: During labor and delivery: 2 mg/kg loading dose followed by continuous iv infusion of 1 mg/kg/hour until delivery. Consider administering loading dose then proceed to delivery

PEP should be given to all newborns born to mothers living with HIV according to local guidelines

Breastfeeding

  • The topic of feeding intentions should be discussed with a pregnant woman as early as possible in pregnancy, together with providing education and support to the mother
  • We advise against breastfeeding, as in high-income settings the optimal way to prevent mother-to-child transmission is to feed infants born to mothers living with HIV with formula milk
    • To reduce the potential physical and emotional discomfort associated with breast engorgement, together with the risk of covert breastfeeding, women living with HIV should be given cabergoline to suppress lactation after delivery
  • In situations where a woman chooses to breastfeed, we recommend input from an interdisciplinary team including adult HIV specialist, paediatrician and obstetrician/gynecologist
    • We recommend monthly follow-up during the whole breastfeeding period with increased clinical and virological monitoring of both the mother and the infant. Measurement of drug concentrations in the milk could be done to inform clinical practice
    • Maternal HIV-VL > 50 copies/mL should result in a stop of breastfeeding, providing cabergoline and support from interdisciplinary team and a nursing specialist
    • Immediate consulting by the interdisciplinary team should be provided in case of signs and symptoms of mastitis, infant mouth or gut infections
    • Currently there is no evidence supporting PrEP recommendation for the infants who are breastfed
    • After stopping the breastfeeding, the child should undergo routine diagnostics as recommended in HIV-exposed children