What are the current recommendations for Antiretroviral Therapy (ART) prophylaxis for infants of Human Immunodeficiency Virus (HIV)-positive mothers, both high-risk and low-risk?

From the Guidelines

Antiretroviral therapy (ART) prophylaxis for infants born to HIV-positive mothers should be tailored to the infant's risk category, with high-risk infants receiving a three-drug regimen and low-risk infants receiving zidovudine monotherapy. For high-risk infants (mothers with high viral load >1000 copies/mL, inadequate ART during pregnancy, or diagnosed with HIV during labor/delivery), a three-drug regimen is recommended: zidovudine (ZDV) 4 mg/kg twice daily, lamivudine (3TC) 2 mg/kg twice daily, and nevirapine (NVP) 6 mg/kg twice daily for 6 weeks 1. For low-risk infants (mothers with viral suppression <50 copies/mL and good ART adherence during pregnancy), zidovudine monotherapy at 4 mg/kg twice daily for 4 weeks is sufficient 1. Some key points to consider include:

• Prophylaxis should begin as soon as possible after birth, ideally within 6-12 hours 1.
• All exposed infants should undergo HIV testing at birth, 2-3 weeks, 1-2 months, and 4-6 months of age 1.
• Breastfeeding is not recommended in resource-rich settings, but if unavoidable, maternal ART and infant prophylaxis should continue throughout the breastfeeding period 1. These regimens effectively reduce perinatal HIV transmission by preventing viral replication during the infant's highest exposure period, with the intensity of prophylaxis matching the level of transmission risk 1. It's also important to note that the choice of antiretroviral regimen in HIV-infected pregnant women must include consideration of fetal drug exposure, while assuring optimal treatment to preserve maternal health 1. The WHO recommends exclusive breastfeeding for HIV-infected women for the first 6 months of life, unless replacement feeding is acceptable, feasible, affordable, sustainable, and safe for them and their infants before that time 1. In resource-limited settings, the WHO recommends a tiered approach for the delivery of antiretroviral to pregnant women who are infected with HIV, including triple-drug antiretroviral treatment for those women who are eligible 1. Overall, the goal of ART prophylaxis is to reduce the risk of perinatal HIV transmission, while also considering the potential risks and benefits of different regimens for both the mother and the infant 1.

From the FDA Drug Label

2.3 Prevention of Maternal-Fetal HIV-1 Transmission 1.2 Prevention of Maternal-Fetal HIV-1 Transmission

The current recommendations for Antiretroviral Therapy (ART) prophylaxis for infants of Human Immunodeficiency Virus (HIV)-positive mothers are not explicitly stated in the provided drug label for zidovudine (PO) 2. However, the label does mention the indication for prevention of maternal-fetal HIV-1 transmission.

• The label does not provide specific recommendations for high-risk or low-risk infants.
• It does not outline the ART prophylaxis regimen for infants of HIV-positive mothers. Therefore, no conclusion can be drawn about the current recommendations for ART prophylaxis for infants of HIV-positive mothers.

From the Research

Current Recommendations for Antiretroviral Therapy (ART) Prophylaxis

The current recommendations for ART prophylaxis in infants of HIV-positive mothers, both high-risk and low-risk, are as follows:

• For high-risk infants, multidrug regimens are recommended to reduce transmission rates, with no significant difference between 2- and 3-drug regimens 3
• For breastfed infants, prolonged ARV prophylaxis (6 months of nevirapine) has been shown to result in lower HIV transmission rates compared to a standard 6-week nevirapine regimen 3
• The World Health Organization (WHO) recommends antiretroviral drugs such as zidovudine, lamivudine, lopinavir/ritonavir, nevirapine, and raltegravir for use in neonates 4
• All infants born to mothers with HIV infection should receive antiretroviral postexposure prophylaxis as soon as possible, ideally within six hours after delivery, with the type of prophylaxis depending on whether the mother has achieved virologic suppression and if the infant is at high risk of vertical transmission of HIV 5

Factors Influencing Transmission Risk

Several factors can influence the risk of transmission, including:

• Maternal viral load: a higher maternal viral load is associated with an increased risk of transmission 6, 7
• Maternal use of illegal substances: maternal use of illegal substances is associated with an increased risk of transmission 6
• Maternal seroconversion during pregnancy or breastfeeding: maternal seroconversion during pregnancy or breastfeeding is a risk factor for vertical transmission of HIV 5
• Advanced maternal HIV disease: advanced maternal HIV disease is a risk factor for vertical transmission of HIV 5

Treatment Regimens

Several treatment regimens have been shown to be effective in reducing mother-to-child transmission (MTCT) of HIV, including:

• AZT/3TC/NVP: this regimen has been shown to decrease MTCT 7
• AZT/3TC/LPV-r: this regimen has been shown to decrease MTCT 7
• AZT/3TC/ABC: this regimen has been shown to decrease MTCT 7