Current recommendations for specific antiretroviral drugs are available in existing guidelines (USA and UK). [9, 30]
Preferred antiretroviral drugs are those with clinical trial data in adults that have demonstrated:
- Optimal efficacy and durability
- Acceptable toxicity and ease of use
- Pregnancy-specific pharmacokinetic (PK) data available to guide dosing
- No associated teratogenic effects
- No reported maternal, foetal or newborn adverse outcomes
Transplacental passage of antiretroviral drugs is an important mechanism of infant pre-exposure prophylaxis (PrEP). For this reason, at least one nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) with a high placental transfer should be included in the ART regimen. The US guidelines currently recommend an ART regimen in pregnancy consisting of two NRTIs and an integrase inhibitor (INSTI) or two NRTIs and a ritonavir-boosted protease inhibitor (PI/r).
Current recommendations January 31, 2024
Current recommendations for the initial commencement of specific antiretroviral drugs in pregnant women, based on the guidelines in the United States, are summarised in Table 5. The guidelines are very extensive regarding prevention of perinatal transmission and interventions during pregnancy. For reasons of brevity, only Table 5 is summarised below. Table 5 presents preferred regimens, for which there are clinical trial data in adults demonstrating optimal efficacy and durability with acceptable toxicity and ease of use, PK data in pregnancy are available, and there is no evidence of teratogenic effects or established adverse outcomes for mother, foetus, and newborn. The full guidelines should be referred to for selection rationale and full antiretroviral drug safety data (http://aidsinfo.nih.gov/guidelines).
Table 5. Preferred initial antiretroviral regimens in pregnancy
Preferred initial regimens are designated as Preferred in the Guidelines when clinical data in adults have demonstrated efficacy and durability and a favourable risk-benefit balance for mother, foetus, and infant outcomes. When considering risks associated with Preferred and Alternative ARVs, the lack of suitable data indicates neither the presence nor absence of risk.
Note, two-drug regimens are NOT recommended in pregnancy.
Also, data suggests decreased drug levels during pregnancy with associated loss of viral suppression with regimens containing cobicistat, e.g., EVG/c or DRV/c, are not recommended for initiation during pregnancy.
| Recommended initial regimens | Additional information |
| Preferred dual NRTI backbone ABC/3TC TAF/FTC or TAF + 3TC TDF/FTC or TDF/3TC |
HLAB5701 negative. ABC not active against hepatitis B When combined with DTG is associated with more treatment-associated obesity in nonpregnant adult women compared to TAF/FDC TDF – potential concerns re foetal bone abnormalities though clinical findings reassuring Potential for renal toxicity – use with caution in patients with renal insufficiency |
| Preferred INSTI regimens DTG/ABC/3TC or DTG + preferred dual NRTIs |
Potential concerns re weight gain |
| Preferred PI regimen DRV/r + preferred dual NRTIs |
Requires twice daily dosing in pregnancy – with food PIs may increase the risk of pre-term birth |
| Alternative initial regimens | Additional information |
| BIC/TAF/FTC | PK and safety data remains limited to small studies T3 drug levels are reduced but remain above EC95 May be associated with weight gain |
| RAL + dual NRTI backbone | Twice daily dosing recommended Lower barrier to resistance than DTG Specific timing/fasting if taken with calcium, iron tabs |
| Alternative PI regimen ATV/r + dual NRTI |
ATV/r plus a preferred two-NRTI backbone – once-daily administration. Extensive experience in pregnancy Maternal hyperbilirubinemia appears to have no adverse effects on the neonate, no maternal clinical significance Increase dosing in T2 and T3 PIs may increase risk of preterm delivery Do not use with PPIs, adjust timing with H2 blockers |
| DRV + dual NRTI | Twice daily dosing – with food PIs may increase risk of preterm delivery |
| Alternative dual NRTI backbone | |
| ZDV/3TC | Twice daily dosing Potential side effects may include nausea, headache, reversible maternal and neonatal anaemia and neutropenia |
| EFV/TDF/FTC (FDC) or EFV/TDF/3TC (FDC) or EFV plus a Preferred dual-NRTI Backbone |
Overall higher rates of adverse events than some Preferred drugs Requires enhanced surveillance for depression and suicidality Increased risk of adverse birth outcomes has been observed with EFV/TDF/FTC versus DTG/TAF/FTC started during pregnancy Increased risk of toxicity, including dizziness, fatigue, hepatotoxicity, vivid dreams/nightmares |
| RPV/TDF/FTC (FDC) or RPV/TAF/FTC (FDC) or RPV (oral) plus a Preferred Dual-NRTI Backbone | Limited use with high pre-treatment HIV RNA RPV is not recommended in patients with pretreatment HIV RNA >100,000 copies/mL or CD4 counts <200 cells/mm3 Requires close viral monitoring in T2 and T3 – PK data suggest lower drug levels Insufficient data to suggest dosing changes Do not use with PPIs Requires consideration of timing with H2 blockers Requires administration with food |
| Insufficient data | |
| DOR or DOR/TDF/FTC | Limited PK, toxicity and efficacy data in pregnancy Initial studies suggest potential low drug levels in T3 |
Source: Recommendations for the Use of Antiretroviral Drugs during Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Updated: January 31, 2024.