What is new in perinatal HIV prevention?

Abstract

Purpose of review: The purpose of this review is to describe recent clinical trial, laboratory and observational findings that highlight both the progress that can be achieved in elimination of new pediatric infections in international clinical trial settings among HIV-infected breastfeeding women while also describing recent safety concerns related to currently used antiretroviral regimens. The article will also address the ongoing adherence challenges for HIV-infected mothers in taking their antiretroviral drugs. This information is timely and relevant as new regimens are being considered for both prevention of mother-to-child transmission (PMTCT) of HIV and HIV treatment options worldwide.

Recent findings: The main themes described in this article include both efficacy of different antiretroviral therapy (ART) regimens currently being rolled out internationally for PMTCT as well as safety findings from recent research including a large multisite international trial, PROMISE.

Summary: The findings from the IMPAACT PROMISE trial as well as other recent trial and observational findings suggest that while progress has been steady in reducing PMTCT worldwide, the goal of virtual elimination of pediatric HIV worldwide will require careful attention to optimizing safety of new regimens which are less dependent on maternal daily ART adherence and safer in preventing certain toxicities.

Figure 1. Increased antiretroviral drug coverage for prevention of mother-to-child transmission of HIV, by Global Plan Priority (GPP) coutry in sub-Saharan Africa (2009–2015). UNAIDS data

Legend: Bar graph. Source UNAIDS 2016 data estimates. Based on [] http://www.unaids.org/sites/default/files/media_asset/GlobalPlan2016_en.pdf (last accessed Oct 18, 2017). PMTCT ARV maternal uptake for 20 UNAIDS GPP countries in sub-Saharan Africa. The presented 2016 estimates do not include Ethiopia. Country-level data were based on proportion of HIV-infected pregnant women who received antiretroviral medicines (excluding single-dose nevirapine only regimens) for PMTCT. Botswana, Mozambique, Namibia, South Africa, Swaziland, and Uganda achieved the UNAIDS 90% coverage by 2015 target set in 2009.

Figure 2. Antiretroviral Therapy Randomized Control Trials for Prevention of mother to child transmission of HIV (1994–2017)

Legend: Presentation of Key Perinatal HIV Prevention Trials, modified from power point slide by Dr. James McIntyre. Key: Lamivudine (3TC); Antiretroviral therapy (ART); US Centers for Disease Control and Prevention (CDC); HIV Prevention Trials Network (HPTN); Nelfinavir (NFV); Nevirapine (NVP); Pediatric AIDS Clinical Trials Group (PACTG); Post-Exposure Prophylaxis (PEPI); Promoting Maternal and Infant Survival Everywhere (PROMISE); Single dose Nevirapine (sdNVP); Six Weeks of Nevirapine (SWEN); Zidovudine (ZDV)

Figure 3. Overall design of the PROMISE 1077BF trial including the Antepartum, Postpartum and Maternal Health components. N=3490

PROMISE Trial 1077 Schema: In the Antepartum Component, pregnant HIV infected women were randomized to one of three regimens: either maternal Zidovudine (ZDV) or one of two Maternal Antepartum Triple Antiretroviral Regimens: antepartum Zidovudine/Lamivudine/Lopinavir/Ritonavir or Tenofovir/emtracitibine/Lopinaovir/RitonavIr. In the Postpartum Component, HIV infected mothers or their newborns were randomized to either receive daily maternal triple antiretroviral prophylaxis, Tenofovir/Emcitrabine/Lopinaovir/Ritonavir; or to daily infant nevirapine, using WHO weight adjusted dosing through 18 months post delivery or cessation of breastfeeding, whichever occurred sooner. In the Maternal Health Component, HIV infected mothers who had been randomized to postpartum Triple ARVs were randomized at entry into Maternal Health Component to either continue or stop triple antiretrovirals at 18 months post delivery; or at the cessation of breastfeeding, whichever occurred sooner. The mothers were then followed to the end of PROMISE. Based on [19].