Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

Abstract

The standard prophylactic regimen used as antiretroviral therapy (ART) for infants born to mothers in high-income and middle-income countries who are infected with human immunodeficiency virus (HIV) infection has been a 6-week course of zidovudine.Randomized controlled trials investigating postexposure prophylaxis for infants born to late-presenting women infected with HIV who did not receive ART in pregnancy have been conducted in breast-fed populations but not in nonYbreast-fed populations. Several trials showed that prophylaxis with combination ART (zidovudine plus Q1 antiretroviral drugs) was effective in reducing viral transmission in high-risk breast-fed populations in low-income countries. However, it is unclear whether prophylaxis with combination ART would prevent intrapartum HIV-1 transmission in nonYbreast-fed infants of women who had not received antenatal ART.This randomized controlled study compared the efficacy and safety of ART prophylactic regimens in a population of solely formula-fed infants whose mothers had not received ART during pregnancy. In designing the study, the authors hypothesized that a 3-drug ART regimen would confer a higher level of protection against intrapartum HIV transmission than a 2-drug regimen. Both regimens were evaluated in this study. Formula-fed infants exposed to HIV-1 were randomly assigned to 1 of 3 ART regimens within 48 hours after birth. Infants in each of the 3 groups received zidovudine for 6 weeks. The first group was given only zidovudine (zidovudine-alone group, n = 566). In addition to zidovudine, the second group received 3 doses of nevirapine during the first 8 days of life (2-drug group, n = 562). The third group received zidovudine plus nelfinavir and lamivudine for 2 weeks (3-drug group, n = 556). The primary study outcome was HIV-1 infection at 3 months of age among infants uninfected at birth. The Kaplan-Meier method was used to estimate transmission rates.The study population included 1684 infants enrolled between 2004 and 2010 at 17 sites in Brazil, Argentina, the United States, and South Africa. The overall rate of in utero transmission of HIV-1 was 5.7% (93 infants); there were no significant differences among the groups. At 3 months, the overall rate of intrapartum transmission was 3.2%. Compared with the zidovudine-alone group, intrapartum transmission at 3 months was reduced by half in the 2-and 3-drug groups: The rate was 4.8% (24 infants) in the zidovudine-alone group versus 2.2% (11 infants) in the 2-drug group and 2.4% Infectious Disease 612

Severe haematologic toxicity is rare in high risk HIV‐exposed infants receiving combination neonatal prophylaxis

“…Serious adverse events possibly related to study drugs were observed in 8.4% of infants, with higher rates in the three‐drug group than in the ZDV‐alone group or the two‐drug group. Neutropaenia and anaemia accounted for the majority of serious adverse events; in particular, grade 2 or greater neutropaenia occurred in 16.4% infants receiving only ZDV and in 15.0% of those receiving two drugs, reaching 27.0% in infants receiving three drugs ( P < 0.0001) .…”

“…However, the optimal prophylactic regimen and the additional efficacy of CNP in reducing MTCT risk in such situations are not well understood. CNP was found to be superior to one‐drug NP in a randomized trial conducted in exclusively formula‐fed infants born to women who had not received ARVs during pregnancy , but data in other high‐risk situations are limited. Furthermore, there is some controversy regarding whether high‐risk newborns should receive therapeutic rather than prophylactic doses of ARVs.…”

“…Data regarding the safety of NP, particularly CNP, are limited in both term and, concerningly, preterm infants. Haematological toxicity associated with in utero or early life exposure to ARVs has been well established, with some studies demonstrating that infants exposed in utero to cART have lower haemoglobin (Hb) levels and neutrophil counts (NCs) than those exposed to ZDV monotherapy or without ART exposure . In the HPTN 040 trial, in which infants had no in utero ART exposure, neutropaenia (grade 2 or above) was more common in the three‐drug arm than in the ZDV/nevirapine (NVP)‐ or ZDV‐only arms, although there was no significant difference with respect to anaemia .…”

What the paediatrician needs to know about HIV‐1 infection

“…In high‐risk children, perinatal prophylaxis should be initiated soon after birth and should include two or three antiretroviral drugs in order to lower the infection risk as much as possible . This approach has been proved to be effective and safe …”

Transmisión vertical del virus de la inmunodeficiencia humana en mujeres usuarias del Centro Hospitalario Pereira Rossell; Uruguay, 2012-2014. Resultados de la aplicación del protocolo zidovudina - nevirapina en niños uruguayos

“…Nielsen-Saines en el año 2012 demostró que la administración de zidovudina por seis semanas con tres dosis de nevirapina o la administración de zidovudina, lamivudina y nelfinavir por 15 días a recién nacidos, hijos de mujeres sin tratamiento antirretroviral en el embarazo o parto fue más eficaz que la zidovudina sola para reducir la transmisión intraparto del VIH al niño (2,2%, 2,4% y 4,8%, respectivamente, p = 0,046). Como los efectos adversos fueron más frecuentes con tres fármacos, la elección de zidovudina con nevirapina comenzó a utilizarse en los casos de mal control del embarazo (13,16) .…”