AEGiS-15IAC: Early detection of HIV-specific T cell responses in infants undergoing combination antiretroviral/structured treament intrerruption intervention in HIV C clade infection in Durban, South Africa.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Early detection of HIV-specific T cell responses in infants undergoing combination antiretroviral/structured treament intrerruption intervention in HIV C clade infection in Durban, South Africa.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1054)

Thobakgale C, Ramduth D, Honeyborne I, Chetty P, Nene N, Ntumba N, Henry C, Brander C, Kiepiela P, Walker BD, Goulder PJ
HPP, University of Natal, Durban, South Africa

BACKGROUND: Life-long dependence upon CART is not a feasible option for infants. The optimal use of CART in paediatric infection has not been determined. To examine the potential for CART, initiated in early paediatric infection, followed by subsequent supervised treatment interruption (STI), to boost HIV-specific immunity, and thereby reduce the requirement for lifelong CART, a pilot study was initiated in Durban, South Africa.

METHODS: Consented infected infants were randomised to one of 3 arms: A) Deferred CART - onset when defined clinical criteria or CD4% levels were met; B) Onset of CART at diagnosis, continued for 12 months, then discontinued; restart as in A; C) Onset of CART at diagnosis, interrupted once VL stably<50 for 9 weeks, restarted once VL>5,000. Repeat CART-STI cycles ending at 18 months' age with final STI; restart as in A. Characterisation of CD8+ T cell responses using a panel of 410 overlapping peptides spanning the expressed genome. Peptides were synthesised based upon the C clade consensus sequence. IFN-g detection was by elispot and intracellular staining (ICS) assays following PBMC stimulation by peptides. CD4+ T cell activity was undertaken by ICS similarly, but included IL-2 measurement.

RESULTS: Currently 10 infants have been enrolled. Four have been enrolled onto Arm A, 3 to Arm B and 3 to Arm C. In infants enrolled onto Arm A, 3/4 had CD8+ T cell responses by week 4. In infants enrolled onto Arms B or C, CD8+ T cell responses have been detectable in 3/6 infants at between 2 and 10 weeks. CD4 responses were detectable in 1/6 infants. Onset of CART is associated with rapid falls in VL and loss of detectable CD8+ T cell responses.

CONCLUSIONS: These preliminary data indicate that CD8+ T cell responses are readily detectable by 4 weeks' age in CART-naïve infants, whereas CD4+ T cell responses are less commonly seen. Further study of these and other enrolled infants will provide valuable insights into the potential role of CART and STI as a means to boost anti-HIV immunity in infected infants.

Keywords: AEGIS, HIV, Acquired Immunodeficiency Syndrome, HIV Infections, HIV Seropositivity, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Anti-HIV Agents, HIV Core Protein p24, HIV Antibodies, Antigens, CD8, Antigens, CD4, HIV Protease Inhibitors, HIV Antigens, Interferon Type II, South Africa, Infant, Humans, Child, immunology

040711
MoOrA1054