HIV Prevention Trials in Infants

A consultation to discuss challenges of conducting trials in HIV-exposed infants.

Testing HIV preventive modalities in infants born to HIV-positive mothers in resource-limited settings (RLS) presents a number of ethical, trial design, and logistical challenges.  Defining the challenges and balancing them against the need to prevent the residual incidence of MTC HIV transmission is critical for making decisions on future clinical trials.  Input on these issues is needed from clinicians, scientists, advocates, government officials, and community representatives from countries where such trials are planned.

The Enterprise and partners convened a consultation in Entebbe Uganda 22 – 23 January 2013 on HIV Prevention Trials in Infants.   Together with the researchers involved in organizing that meeting, the Enterprise published a paper focusing on the opportunities presented by the discovery of broadly neutralizing antibodies (bNAbs) to HIV: HIV Monoclonal Antibodies: A New Opportunity to Further Reduce Mother-to-Child HIV Transmission.  While highlighting the great advances that were made with antiretroviral (ARV) therapy in preventing mother-to-child HIV transmission (MTCT), they state that “it appears unlikely that the goal of global elimination will be met with current ARV interventions alone, and continued investigation of preventive interventions to reduce MTCT, including maternal and/or infant passive/active immunization, remains important.”  In the paper, the authors discuss the various factors that impact the translation of these antibodies from basic discovery into the clinical trials, including the choice of the product, costs, and complexities of conducting efficacy trials in this vulnerable and hard-to-reach population.  They also use a proposed passive immunization trial with the monoclonal antibody VRC01 as a case study to explore the conduct of trials in infants exposed to HIV-1 via breastfeeding.

Organizing Committee:

  • Dr. Jeffrey Safrit, Elizabeth Glaser Pediatric AIDS Foundation, USA
  • Dr. Coleen Cunningham, Duke University, USA
  • Dr. Mary Glenn Fowler, Makerere University/Johns Hopkins University, Uganda
  • Dr. Barney Graham, Vaccine Research Center, USA
  • Dr. Pontiano Kaleebu, MRC-Uganda, Uganda
  • Dr. Betsy McFarland, University of Colorado, USA
  • Dr. Lynne Mofenson, NIH/NICHD, USA
  • Dr. Yegor Voronin, Global HIV Vaccine Enterprise, USA

Meeting Objectives

  • Produce a position statement with recommendations on the conduct of preventive MTCT trials in breastfed infants of HIV+ mothers from vulnerable populations in developing countries
  • Provide recommendations on trial design and logistical challenges in potential passive immunization trials using the VRC01 mAb by the IMPAACT network as an example, including, but not limited to:
    • Current state-of-the-art PMTCT regimens vs standard-of-care in RLS: what regimens need to be offered for PMTCT in the context of a clinical trial?
    • Rationale for testing preventive strategies in infants in RLS without first having done similar studies in the US or other developed countries.
    • Informed consent in women during the late stages of pregnancy.
    • Sample size based on anticipated changes in incidence over time.


Despite our knowledge and best efforts to date, there are still up to 1000 infants infected with HIV every day.  While the state of the art PMTCT regimens block 99% of transmissions, many pregnant women don’t have access to the necessary services.  In the absence of access to clean water and baby formula, WHO recommends breastfeeding as a way to reduce infant mortality in developing countries.  Other HIV prevention modalities are needed in addition to daily antiretroviral drugs1.  Passive immunization with recently discovered broadly-neutralizing antibodies presents a potential prevention approach, which can also inform design and testing of pediatric vaccine candidates2.

Infants have been involved in HIV vaccine research although no vaccine efficacy trials have been performed in this population3–5.  Previous studies, conducted in the USA and Uganda, have demonstrated safety and immunogenicity of envelope-based vaccines and different ALVAC vaccine constructs in young infants born to HIV-infected women, where they showed immunogenicity similar to that seen in adults6–8.  A previous collaboration between EGPAF, IMPAACT, HVTN and Merck to test the Merck Ad5 vaccine in a breastfeeding population in sub-Saharan Africa was abandoned after the STEP trial results became available.  Further progress in this area was limited to the search of vaccine candidates that product developers would be willing to test.

Previous attempts at passive immunization of infants at risk for HIV infection either failed to show efficacy or were not initiated due to concerns of auto-reactivity of the antibodies available at the time. Recent discoveries of antibodies which are orders of magnitude more potent and broad, and are not auto-reactive, present a new opportunity in this area.  A new collaboration between VRC, IMPAACT and EGPAF is considering several trials of the VRC01 antibody, including two trials in breastfed infants, first looking at safety and feasibility, and later at efficacy.  Design of these studies and of the above mentioned vaccine trials in breastfed infants present a number of challenges, which need to be thoroughly discussed  in a transparent fashion among the relevant stakeholders.

Opinions, Commentaries, and Discussion

From Scarcity to Abundance. Who decides the priority for clinical trials in resourse poor countres? by Arthur Ammann

Comment on Ethics of PMTCT Research by Nigel Rollins

If you have any questions or comments about the topic, or would like to highlight a particular aspect that should be discussed during the meeting, please use the comments form below.


  1.  Mofenson, L. M. Prevention of mother-to-child HIV-1 transmission–why we still need a preventive HIV immunization strategy. J. Acquir. Immune Defic. Syndr. 58, 359–362 (2011).
  2. Guay, L. A. et al. Phase I/II trial of HIV-1 hyperimmune globulin for the prevention of HIV-1 vertical transmission in Uganda. AIDS 16, 1391–1400 (2002).
  3. Safrit, J. T. HIV vaccines in infants and children: past trials, present plans and future perspectives. Curr. Mol. Med. 3, 303–312 (2003).
  4. Safrit, J. T. et al. Immunoprophylaxis to prevent mother-to-child transmission of HIV-1. J. Acquir. Immune Defic. Syndr. 35, 169–177 (2004).
  5. Cunningham, C. K. & McFarland, E. Vaccines for prevention of mother-to-child transmission of HIV. Curr Opin HIV AIDS 3, 151–154 (2008).
  6. McFarland, E. J. et al. HIV-1 vaccine induced immune responses in newborns of HIV-1 infected mothers. AIDS 20, 1481–1489 (2006).
  7. McFarland, E. J. et al. Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine. J. Infect. Dis. 184, 1331–1335 (2001).
  8. Ssewanyana, I. et al. Immunogenicity of ALVAC-HIV vCP1521 in infants born to HIV-1 infected women in Uganda (HPTN 027). AIDS Vaccine meeting 2007.

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