Table 3.

Challenges of FDA-approved anti-HIV therapeutic antibodies development.

Challenge	Notes	References
Method	Phage-display library is the most commonly used technique for therapeutic antibody generation.	[53]
	The technique allows both genetic and chemical modification of antibody fragments.	[54]
Cost	The production cost of antibody is higher than the synthesis of small-molecule antivirals. The generation of recombinant antibodies results in higher manufacturing cost.	[21]
Host immunology	Individuals' immune responses towards therapeutic antibodies may be different	[55]
Epidemiology	Geographical distribution affects the resistance mechanism and neutralization escape of viral strains	[56]
Delivery	Conjugation with cell-penetrating peptides improves the cellular delivery of antibodies. Smaller antibody formats such as Fabs, sdAbs, and scFvs also facilitate tissue delivery	[57]
Stability	Fc region engineering improves the half-life, stability, and the effector function of the antibody	[58]
Resistant mutants	Development of antibody-resistant HIV mutants has been reported in VRC01-treated patients, combination therapy will minimize the occurrence of virus mutation	[45]
Toxicity	IL-2 and IFN-γ therapy that may be used as adjuvant therapy for bnAbs therapy to stimulate T-cell killing and HIV-1 transcription resulted in high level of cytotoxicity	[59]