Current HIV basic science research topics

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.

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.

Very Early Treatment of a Second Perinatally HIV- Infected Infant

HIV DNA + (age 4 hrs)HIV RNA + (age 36 hrs); 217 copies/mL

AZT/3TC/NVP4 hrs of Age-

High risk exposure: untreated maternal infectionMaternal pvL near delivery =138,811 copies/mL;CD4=70 cells/mm3

Miller Children’s Hospital: Deveikis A; Batra J and Michalik D.

Very Early Treatment of a Second Perinatally HIV- Infected Infant (Persistent HIV RNA through DOL#6)

HIV DNA + (age 4 hrs)HIV RNA + (age 36 hrs); 217 copies/mL

AZT/3TC/NVP4 hrs of Age-

CSF+-HIV RNA (DOL#6)=32 copies/mL

Miller Children’s Hospital: Deveikis et al.

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

Biomarker Age at Testing (months)

cART Duration(Months)

Finding

Plasma viral load (copies/ml) 0.36 (11 days) 0.36 <201.6 1.6 <202.2 2.2 <204.6 4.6 <206.2 6.2 <209.5 9.5 <20

Proviral DNA (Clinical Assay) 0.2 (6 days) 0.2 (6 days) negative1.6 1.6 negative2.2 2.2 negative

Infectious Virus Recovery (IUPM) 1 1 <0.133 3 <0.209 9 <0.15

Non-Induced Proviral Genomes 1 1 positive

3 3 negative9 9 negative

Proviral DNA (ddPCR)/per Million PBMCs 3 3 <6.39 9 <1.6

HIV Serostatus (Western Blot) 9 9 Seronegative

JB Whitney et al. Nature 000, 1-4 (2014) doi:10.1038/nature13594

Viral decay kinetics after treatment with ART.

JB Whitney et al. Nature 000, 1-4 (2014) doi:10.1038/nature13594

Proviral DNA during ART.

JB Whitney et al. Nature 000, 1-4 (2014) doi:10.1038/nature13594

Viral rebound kinetics after ART discontinuation.

Host restriction factors

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

Blocking molecules

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

Berlin PatientAlso 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 TransplantsThe 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/