Important note: Information in this article was accurate in August 2004. The state of the art may have changed since the publication date.
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HIV Treatment Bulletin - Vol. 5, No. 7, August/September 2004
Simon Collins, HIV i-Base
The continued use of 3TC to maintain 3TC-associated M184V mutation because of the theoretical impact on viral fitness is supported by several early and persuasive studies. However, no clinical benefit was found in the long-enrolling Colate study when results were eventually presented earlier this year at CROI. [1] Colate had randomised patients on failing 3TC-containing treatment to either stop or maintain 3TC in their subsequent regimen.
Castagna and colleagues from Vita-Salute San Raffaele University, Milan took a different approach. They randomised patients failing treatment (median VL approx 7,000, IQR 3,000 – 15,000) with relatively high CD4 counts (median > 600 cells/mm3, IQR approx 560-750) to either discontinue treatment completely (arm A) or continue with 3TC monotherapy (arm B). The primary endpoint was progression to immunological failure defined as CD4 count failing to <350 cells/mm3. [2]
Results were presented on 45/50 pts: 24 in arm A and 21 in arm B. Discontinuation occurred in 21 patients due to viral failure, one patient who withdrew consent and one patient with oesophageal thrush, and occurred more frequently in patients who discontinued all treatment 14/24 (58%) vs 9/21 (43%).
Although statistical significance analysis was not provided, the nine patients remaining on study taking 3TC showed a protective effect on both CD4 count and virological rebound.
Median (IQR) change in CD4 and viral load:
| Arm A (N=22; NoRx | Arm B (N=18; 3TC mono) | |||
| Disc. | On Study | Disc. | On Study | |
| N | 14 | 8 | 9 | 9 |
| Delta CD4 | -169 | -187 | -111 | +23 |
| (IQR) | (-278/-110) | (-259/-9) | (-159/-93) | (-43/+38) |
| ~ delta VL | 91k | 76k | 15k | 6.6k |
| (IQR) | (42-124k) | (58-160) | (13k-20k) | (1k18k) |
The study concluded that these preliminary results support the hypothesis that 3TC monotherapy reduces the frequency of immunological failure and induces less viral rebound than therapy interruption.
Comment
These results are very interesting, despite low numbers (and lack of statistical analysis!). The interest in a beneficial effect of using 3TC is of course driven by its low toxicity. The cost of 3TC is likely to fall further once 3TC comes off-patent.
It is frustrating that from the tens of thousands of people either using 3TC or with 184V resistance that a larger set of supporting data for this simple approach has still not been assembled.
References:
| 1. | Dragsted U, Fox Z, Mathiesen L et al for the COLATE trial group. Final week 48 analysis of a Phase IV, randomised, open-label, multi-centre trial to evaluate safety and efficacy of continued 3TC twice-daily versus discontinuation of 3TC in HIV-1-infected adults with virological failure on ongoing combination treatments containing 3TC: the COLATE trial. 11th CROI 2004, Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: Abstract No. 549. See, also, Simon Collins, "COLATE study shows no clinical benefit from continuing 3TC to maintain M184V mutation", HIV Treat Bull 2004 Apr 5(3). |
| 2. | Castagna A, Danise A, Carini E et al. E-184V. Pilot study to evaluate immunological response to lamivudine monotherapy vs treatment interruption in failing HIV-1 infected subjects, harbouring the M184V mutation. XV Intl AIDS Conference, Bangkok. Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. WeOrB1286. |
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