dual bnab treatment in children

Conditions: HIV Infection

Summary: the purpose of this study is to evaluate the impact of two broadly neutralizing antibodies, vrc01ls and 10-1074, on the maintenance of hiv suppression in a cohort of early-treated children in botswana.

this study will evaluate the impact of two broadly neutralizing antibodies, vrc01ls and 10-1074, on the maintenance of hiv suppression in a cohort of early-treated children in botswana. the primary objectives are as follows: 1. to conduct an interventional clinical trial to determine the safety, pharmacokinetics, dosing and antiviral efficacy of up to 24 weeks of maintenance vrc01ls and 10-1074 immunotherapy in early-treated hiv-1 infected children in botswana. 2. to evaluate effects of treatment with vrc01ls and 10-1074 on the size and cellular composition of residual viral reservoirs. 3. to investigate the influence of vrc01ls and 10-1074 treatment on the magnitude and quality of antiviral innate and adaptive immune responses. the study includes 4 steps: the pharmacokinetics (pk) step, step 1, step 2, and step 3. in the pk step, antiretroviral treatment (art) is continued and 12 study participants will undergo safety and pk testing, 6 for each bnab used in the study (10-1074 and vrc01ls). in step 1, art is continued and dual bnab treatment occurs, with pk confirmation of dual bnab dosing for the first 6 participants in step 1. in step 2, art is withdrawn and dual bnab maintenance treatment occurs. in step 3, dual bnabs will be discontinued and participants will be re-started on art. participants will be in the study for a minimum of 56 weeks, and a maximum of 98 weeks for those who start in the pk step and continue through the study.

Eligibility criteria:
inclusion criteria for pk step\*: * on art for at least 96 weeks * greater than or equal to 96 weeks and less than 5 years of age at enrollment * hiv rna less than 40 copies/ml for at least 24 weeks prior to entry * ability to remain in close study follow-up for at least 12 weeks * willingness to receive iv infusions of bnabs * willingness to provide signed informed consent (by the parent/guardian) * \*it is anticipated that all children in pk step will be from early infant treatment (eit) study (nct02369406); however, up to 4 hiv+ children outside the pk study (age range 2-5 years) may participate in the pk step if otherwise eligible and if eit children are unavailable. inclusion criteria for entry into step 1 (followed by participation in steps 2-3): * eit study participant (nct02369406) * on art for at least 96 weeks * greater than or equal to 96 weeks and less than 7 years of age at enrollment * hiv rna less than 40 copies/ml for at least 24 weeks prior to entry * ability to remain in close study follow-up for at least 56 weeks * willingness to receive iv infusions of bnabs * willingness to provide signed informed consent (by the parent/guardian) exclusion criteria: * medical condition making survival for at least 32 weeks unlikely * active tuberculosis or malignancy * actively breastfeeding * previous receipt of vrc01/vrc01ls or 10-1074 (except during the pk step)

Keywords: broadly neutralizing antibodies hiv suppression