Current HIV basic science research topics

1. Current HIV basic science research topics

2. Toddler "Functionally Cured" of HIV Infection- “the Mississippi Baby” • First well-documented case of an HIV infected child that appeared to be functionally cured • Born prematurely in Mississippi to an HIV infected mother (no HAART) • The infant was put on liquid therapy at 30 hours of age and kept on drugs until 18 months of age • Tests at the time revealed undetectable viral RNA, no anti-HIV antibodies, very low viral DNA levels • Virus resurfaces in infected child 27 months after antiretroviral therapy stopped.

3. Toddler "Functionally Cured" of HIV Infection- “the LA Baby” • Second case of an HIV infected child that appeared to be functionally cured • The infant was put on AZT/3TC/NVP at 4 hours of age and is still on drugs. • Viral RNA/DNA detected before therapy, negative after. • Child is still virus free.

4. Very Early Treatment of a Second Perinatally HIV- Infected Infant High risk exposure: untreated maternal infection Maternal pvL near delivery =138,811 copies/mL;CD4=70 cells/mm3 AZT/3TC/NVP 4 hrs of Age- HIV DNA + (age 4 hrs) HIV RNA + (age 36 hrs); 217 copies/mL Miller Children’s Hospital: Deveikis A; Batra J and Michalik D.

5. Very Early Treatment of a Second Perinatally HIV- Infected Infant (Persistent HIV RNA through DOL#6) AZT/3TC/NVP 4 hrs of Age- CSF+-HIV RNA (DOL#6)=32 copies/mL HIV DNA + (age 4 hrs) HIV RNA + (age 36 hrs); 217 copies/mL Miller Children’s Hospital: Deveikis et al.

6. Rapid Loss of Detection of HIV Infection During Very Early cART (Case #2)

7. Viral decay kinetics after treatment with ART. JBWhitneyet al. Nature 000, 1-4 (2014) doi:10.1038/nature13594

8. Proviral DNA during ART. JBWhitneyet al. Nature 000, 1-4 (2014) doi:10.1038/nature13594

9. Viral rebound kinetics after ART discontinuation. JBWhitneyet al. Nature 000, 1-4 (2014) doi:10.1038/nature13594

10. Host restriction factors

11. Host restriction factors • Naturally occurring proteins in cells that are resistant to the virus • Identified to block certain steps of the virus life cycle • Quite popular as they have the potential to develop into new therapies against HIV • Most recent one – SAMHD1 • Once HIV enters the cells it immediately seizes its molecular material to reproduce like the building blocks to make virus DNA. • SAMHD1 will damage these building bocks preventing virus replication

12. Blocking molecules

13. Blocking molecules • CXCL4 or PF-4, binds to HIV and prevents attachment to or entry into a human cell • AIDS researchers isolate new potent and broadly effective antibodies against HIV • http://www.sciencedaily.com/releases/2011/08/110817130959.htm

14. Berlin Patient Also known as Timothy Brown. Many years on HAART until he developed lymphoma. Stem cells transplants from a matched donor, homozygous for the CCR5∆32 mutation. He is not on HAART anymore, and free of virus. Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation. N Engl J Med 2009; 360:692-698 On July 3… Researcher Reports Two HIV Patients Showing No Signs of Virus in Wake of Stem-Cell Transplants The patients underwent reduced intensity chemotherapy followed by stem-cell transplants. No sign of rebound yet. http://www.amfar.org/amfar-researcher-reports-two-hiv-patients-showing-no-signs-virus-wake-stem-cell-transplants-cure-research/