Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal

Table 6 SIV-specific antibody responses in plasma at the end of tenofovir treatment and after tenofovir withdrawal

		SIV-specific binding IgG¹	Neutralizing antibody ID50 in TZM-bl cells²				ADCVI³
		SIV-specific binding IgG¹	Neutralizing antibody ID50 in TZM-bl cells²				% inhibition of 1:100 serum dilution
Animal number	Time point		SVA-MLV	SIVmac239CS.23	SIVmac251-CS	SIVmac251-TCLA	SIVmac251-CS	SIVmac251-TCLA	SIVmac251 (UCD)	RT-SHIV
29276	Euthanasia	409,600	20	<10	17	29,462	48.89	99.98	99.99	nd
30577	TFV withdrawal	409,600	<10	<10	12	380,644	61.77	99.94	93.49	99.89
“	Euthanasia	409,600	<10	13	11	>1,562,500	33.29	99.94	94.48	99.89
32186	TFV withdrawal	1,638,400	<10	<10	10	>1,562,500	99.98	99.98	99.99	nd
“	Euthanasia	1,638,400	<10	<10	<10	>1,562,500	99.98	99.98	99.06	nd
33088	TFV withdrawal	409,600	<10	<10	13	451,911	99.98	99.98	99.99	nd
“	Euthanasia	409,600	<10	<10	<10	>1,562,500	99.78	99.98	99.99	nd
33091	TFV withdrawal	6,553,600	<10	<10	10	>1,562,500	99.98	99.98	99.99	nd
“	Euthanasia	6,553,600	<10	<10	12	>1,562,500	99.98	99.98	99.99	nd

¹Values of SIV-binding antibody titers are the reciprocal of the highest plasma dilution (of 4-fold dilutions) that gave a positive signal on whole-virus antibody ELISA assay specific for IgG.
²Values of neutralizing antibody are the serum dilution at which relative luminescence units (RLUs) were reduced 50% compared to virus control wells (no test sample); viruses tested were pseudoviruses SIVmac239CS.23 and SVA-MLV grown in 293 T cells, and replication-competent SIVmac251-CS (hPBMC-grown) and uncloned SIVmac251-TCLA (H9-grown; tissue culture lab adapted).
³ADCVI: antibody-dependent cell-mediated virus inhibition was tested at a 1:100 serum dilution with SIV-infected CEM.NKr R5 as targets and human PBMC as effector cells. The reported values of % inhibition are the averages of 2 independent experiments. The SIVmac251CS and SIVmac251-TCLA are the same as those used in the neutralizing antibody assay; SIVmac251 (UCD) is a stock grown in rhesus PBMC derived from the same seed stock as the SIVmac251 stock that was used to inoculate animals 32186, 33088 and 33091. The RT-SHIV stock was grown in rhesus PBMC from the same seed stock used to infect animal 30577. Only serum of RT-SHIV infected animal 30577 was tested for ADCVI activity against RT-SHIV. nd indicates not done.

ISSN: 1742-4690