Table 1.
Inhibition of HIV-1 replication by ACV in tonsillar tissues ex vivoa
| Strainb | HIV replicationc |
% Inhibition by ACVd |
|||
|---|---|---|---|---|---|
| Untreated control | ACV |
3 μM | 30 μM | ||
| 3 μM | 30 μM | ||||
| Primary HIV-1 isolates | |||||
| HIV-1LAI.04 | 13,052 (4,508–19,484) | 7,714 (1,487–12,305) | 749 (267–3,238) | 47 ± 17 | 83 ± 15 |
| HIV-196USNG31 | 4,455 (566–27,716) | 3,836 (608–16,167) | 871 (175–2,031) | 20 ± 18* | 71 ± 13 |
| HIV-197USNG30 | 14,050 (4,373–71,055) | 12,926 (3,568–46,592) | 7,438 (1,404–24,983) | 54 ± 22 | 82 ± 21 |
| HIV-196USNN20 | 5,365 (3,351–10,700) | 4,832 (2,017–10,142) | 2,059 (596–5,403) | 34 ± 26 | 68 ± 18 |
| HIV-1ME1 | 4,462 (2,166–6,919) | 2,263 (1,137–3,287) | 261 (215–336) | 53 ± 11 | 91 ± 6 |
| AZT-resistant variant HIV-1AZT.4X | 18,006 (15,618–30,906) | 10,325 (9,033–15,529) | 6,946 (6,573–9,967) | 57 ± 3 | 74 ± 7 |
| Lamivudine-resistant variant HIV-1M184V | 33,750 (27,305–44,612) | 37,165 (28,921–43,976) | 10,103 (8,118–14,408) | 14 ± 18* | 65 ± 27 |
| Multi-NRTI-resistant variants | |||||
| HIV-17324–4 | 1,904 (752–4,139) | 791 (203–1,782) | 67 (0–598) | 58 ± 17 | 92 ± 12 |
| HIV-110076–4 | 4,664 (513–11,393) | 1,415 (360–13,650) | 29 (13–627) | 57 ± 42 | 90 ± 15 |
| HIV-16463–13 | 793 (577–16,866) | 782 (550–17,295) | 33 (17–3,359) | 4 ± 7* | 90 ± 10 |
| HIV-17303–3 | 3,389 (1,940–10,550) | 2,524 (867–7,047) | 1,054 (253–4,206) | 31 ± 26 | 73 ± 29 |
| HIV-11617–1 | 12,559 (1,693–34,307) | 9,125 (2104–23,525) | 1,861 (216–4,273) | 18 ± 15* | 88 ± 13 |
| HIV-135764–2 | 933 (818–9,311) | 295 (211–3,349) | 98 (91–302) | 55 ± 31 | 91 ± 11 |
| Nevirapine-resistant variant HIV-1N119 | 52,832 (18,027–139,405) | 8,019 (6,935–9,104) | 16,599 (6,152–29,579) | 55 ± 51 | 84 ± 12 |
| Fusion inhibitor-resistant variant HIV-1pNL4–3 gp41(36G)/V38A/N42D | 1,043 (778–2,881) | 619 (600–1,174) | 48 (44–56) | 35 ± 32 | 94 ± 6 |
| Protease inhibitor-resistant HIV-1 variants | |||||
| HIV-1L10R/M46I/L63P/V82T/I84V | 23,863 (18,986–31,508) | 12,590 (11,524–15,546) | 902 (614–1,148) | 40 ± 37 | 96 ± 2 |
| HIV-1M46I/L63P/V82T/I84V | 4,410 (287–10,834) | 3,685 (55–8,507) | 348 (24–1,095) | 47 ± 31 | 86 ± 11 |
For each isolate and each experimental condition, 27 tonsillar tissue blocks were inoculated with each HIV-1 isolate from a multi-NRTI-resistant HIV-1 panel and treated for 12 days with 3 or 30 μM ACV.
Multi-NRTI-resistant clone HIV-17324-4 carried the mutations 41L, 70R, 215F, and 219E on its reverse transcriptase. HIV-110076-4 carried mutations 41L, 215Y, and 184V. HIV-16463-13 carried the mutations 41L, 67N, 210W, 215Y, 184V, and 118I. HIV-17303-3 carried the mutations 41L, 67N, 201W, 215Y, 69D, 44D, and 118I. HIV-11617-1 carried the mutations G70, 184V, 69K, 75I, 77L, 116Y, and 151 M. HIV-135764-2 carried the mutations 75I, 77L, 118Y, and 151 M (11).
For each viral isolate, the median cumulative p24gag release (pg/ml) and interquartile range (25 to 75%) in culture supernatant of infected tissues were calculated from n independent experiments. n = 3 to 7 for all conditions (except HIV-1AZT.4X replication in the untreated control and HIV-1N119 in the 3 μM ACV-treated condition, where n = 2).
Percentage (mean ± SD) of inhibition of HIV replication by 3 or 30 μM ACV is defined as [1−(RACV/RCtl)] × 100, where RACV and RCtl are the amounts of p24 accumulated in the medium over the 12-day culture period in ACV-treated cultures and in donor-matched untreated cultures, respectively.
, P < 0.05 (inhibition of replication of HIV variants compared to reference strain HIV-1LAI.04).