Did you know that another part was also updated?

Perinatal Guidelines: Part II

All children born to HIV-seropositive women are recommended to initiate antiretroviral (ARV) therapy; however, the decision in selecting ARVs for prophylaxis depends on the situation.  There are a few settings to consider for neonatal prophylaxis:

1.    HIV-positive mother who was on antepartum HAART and is virologically controlled

2.    HIV-positive mother was NOT on antepartum HAART (with or without intrapartum IV zidovudine)

3.    HIV-positive mother who was on antepartum HAART but is NOT virologically controlled

4.    HIV-positive mother was has known ARV-resistant virus

In setting 1, neonates should receive 6 weeks of oral zidovudine (AZT); the most recent dosing recommendation was discussed in the previous blog.  In settings 3 and 4, it is highly recommended to contact the National HIV/AIDS Clinicians’ Consultation Center Perinatal HIV Hotline (available at 1.888.448.8765) to discuss the optimal combination of ARVs.  The 2011 Prevention of Mother to Child Transmission has new recommendations for ARV prophylaxis in setting 2.

Previously, it was recommended to provide 6 weeks of AZT, a single-dose of nevirapine (NVP) and 7 days of lamivudine (3TC) to neonates; it was recognized that even a single dose of nevirapine could lead to drug-resistant virus and a “tail” of 3TC could decrease the risk.  However, side effects, such as neutropenia, were more common in this combination of ARVs.

The NICHD HPTN 040/PACTG 1043 sought to compare the efficacy and safety of 3 regimens to prevent intrapartum transmission of HIV-1 in neonates whose mothers did not receive antepartum HAART (but could receive intrapartum IV AZT:

1.    AZT x 6 weeks alone (n = 566)

2.    AZT x 6 weeks with 3 doses of NVP (n = 562)

3.    AZT x 6 weeks with 3TC and nelfinavir (NFV) x 2 weeks (n = 556)

Of the 1684 neonates who were evaluable for the study, 140 neonates were infected with HIV, of which 47 were from intrapartum transmission. The transmission rate in each group: AZT alone group = 4.9%, AZT + NVP = 2.2%, and AZT +3TC/NFV = 2.5%; the rate was considered significantly lower in the patients who received combination therapy compared to AZT alone (p = 0.045 for both).  A high viral load (the median viral load was log ₁₀ 4.17) and drug abuse was associated with intrapartum transmission of HIV; I think that this is particularly interesting since the current guidelines recommend a Cesarean section if the viral load > 1000 copies/mcL and in this study, a majority of women had a natural birth (65%) and transmission was not associated with the mode of birth.  On the other hand, there were a small number of patients with intrapartum transmission and the study may not have been powered to look at this association.  When looking at safety of the ARVs, it was found that group 3 had a significantly higher rate of neutropenia (p < 0.0001); other factors, such as anemia, transaminitis, or thrombocytopenia was similar amongst all groups.

Due to the increased efficacy in comparison to AZT alone, and lesser toxicity in comparison to the 3-drug regimen, it is now recommended to provide 6 weeks of AZT and 3 doses of NVP to the neonate where HIV-seropositive mothers did not receive antepartum HAART.

Of note, the infants included in this study were NOT breastfed; formula was provided to the family through the study.  The ideal ARV regimen for neonates who are breastfed by HIV-seropositive mothers is still under investigation.

1.       Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. May 24, 2010; pp 1-117.

2.       Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Sep. 14, 2011; pp 1-207. Available at http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf.

3.       Nielsen-Saines K, Watts DH, Santos VV, et al. Phase III randomized trial of the safety and efficacy of three neonatal antiretroviral regimens for preventing intrapartum HIV-1 transmission (NICHD HPTN 040/PACTG 1043). Paper presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI); Feb. 27-Mar 3, 2011; Boston, MA.