Paediatric AIDS - Reservoirs

My notes from the Thursday Morning Plenary

Professor Deborah Persaud – Paediatrics Johns Hopkins University School of Medicine. Known for the “Mississippi Baby”. Time magazine top 100 most influential people in 2013.

Children with HIV - 2.6 mil

New HIV in 2014 - 220 000

Deaths due to AIDS in 2014 -150 000

Decreasing number of mother to child transmission around the world due to treatment.

Early treatment of babies in the perinatal treatment allows a 99% survival at 6 years. Without treatment 50% die by age 2.

Effects of HIV in Children: Lipoatrophy, substance abuse, bone disorder, mental health issues, learning disabilities, abnormal lipids, STIGMA

Barrier to HIV -1 Cure

• Viral Reservoirs. Sites that protected the virus from antiretrovirals. Within 2 weeks of cessation of treatment, the virus returns.

• Exists in resting memory CD4 T Cells. Memory response after naïve cells are activated by initial HIV infection. Cells are present all over the body. High concentration in lymphoid tissue. They have a half-life of 3.6yrs. An Adult would need to take ARV for 78 yrs to get rid of 1000000 million memory CD4 Cells.

• Treating a child for 10 years doesn’t change the rebound time of 2 weeks.

Goals of HIV -1 Cure

• Eradicate latent reservoir (as in the Berlin patient)

  • Bone marrow transplants for those who need BMT for other conditions

• Control viral rebound off ART (Sustained Virologic remission)

  • Early treatment to limit reservoir. Other immunosuppressive treatment.

Infant Immune System

• Lower immune cell activiation. Slower memory cells. Less memory cells.

• Unlike adults early treated children end up having a much lower number of infected cells/reservoir.

• This shows that the reservoir doesn’t evolve over time.

Very Early ART at less than 48hrs of age (Mississippi Baby)

Baby was started on AZT 3TC and Neviripine. Started within 48hrs but not immediately after birth due to lack of resources at location of birth. Drug was ceased at 18 months. At this time there was no plasma viremia, no HIV antibodies, no latent reservoir. No protective genetic alleles. No evidence of immune response. The child however ended up having a vira rebound at 27 months.  Small latent reservoir can lay dormant for 1-2 yrs when child is treated very early.  No adverse effects of rebound and child was effectively treated after to viral suppression.

 Findings – early treated with ARV is feasible safe, and ideal.

AZT, 3TC, Nevirapine is the only current recommended treatment for immediate treatment. Kaletra can be used from 2 months.

Long acting injectables to neutralize antibodies early on to reduce reservoir in early infancy are currently being developed to last for 6 months.