FTC studies at EACS: reduced incidence of M184V compared to 3TC; side effect profile in clinical practice

11 February 2006. Related: Conference reports, Antiretrovirals, EACS 10 Dublin 2005.

Simon Collins, HIV i-Base

After a relatively long and low profile development, FTC (emtricitabine) was licensed in Europe in October 2003. It quickly became included in UK and US treatment guidelines as a drug that is interchangeable with 3TC (lamivudine), with which it shares a similar chemical structure and resistance pattern.

Although 3TC was recently licensed as a once-daily drug, the plasma and intracellular half-lives of FTC (10 hours versus 7.9 hours; and > 39 hours versus 16 hours) are longer than that of 3TC, providing a theoretical advantage for FTC in terms of late or missed doses. This advantage has not been shown to produce a clinical advantage over 3TC in studies.

McColl and colleagues from Gilead pooled results from three Phase III studies that included either FTC or 3TC in various regimens with efavirenz plus another RTI. [1] The studies were FTC-301 (FTC/ddI/EFV vs d4T/ddI/EFV), GS903 (3TC/TDF/EFV vs 3TC/d4T/EFV) and GS934 (FTC/TDF/EFV vs 3TC/AZT/EFV). The frequency of M184V/I mutation was analysed in each group.

A total of 522 patients were treated with FTC QD and 841 patients were treated with 3TC BID. Failure rates in these studies were generally low. When looking at ‘time to loss of virological response (TLOVR), 3/14 (21%) FTC patients and 20/37 (54%) 3TC patients developed M184V/I. Using the denominator of all patients treated: 3/522 (0.6%) FTC patients vs 20/841 (2.4%) 3TC patients developed M184V/I (p=0.015). Results were similar when the criteria for virologic failure were confirmed >400 copies/mL. Of these failures, 5/26 (19%) FTC and 27/75 (36%) 3TC patients developed M184V/I. Using the denominator of all patients treated: 5/522 (1%) FTC patients and 27/841 (3.2%) 3TC patients developed M184V/I (p=0.009).

Two other studies from the conference provided new information on use of FTC in clinical practice.

Pollock and colleagues from the Chelsea and Westminster Hospital in London performed a retrospective review of case notes of patients who subsequently switched back to 3TC after a change to FTC. A total of 158 patients made the initial switch from 3TC to FTC. Of these 13 switched back (8%) The most common cause for intolerance to FTC was mood/psychological disturbance (38%) Other reasons included diarrhoea or GI symptoms (23%) or aching muscles (18%)

The study concluded that ‘although FTC has been introduced as a well tolerated once a day drug, the results suggest this is not the case in all patients’ and ‘raises the possibility of a psychological side effect that needs further evaluation’.

Rawlings and colleagues from the Peabody Health Center, Dallas, and Gilead Sciences conducted a prospective study in 200 patients of African decent to further characterise hyperpigmentation of the palms that is reported as a side effect of FTC.

All patients were evaluated for any appearance of pigmentation changes on palms, soles, oral mucosa, and other body parts periodically, with photographs of the palms of the hands taken against an 18% grey background at a distance of 90 cm. Photographs were then reviewed to evaluate the prevalence of freckling (skin discoloration) by clinical staff.

44 (22 %) of the 200 patients of African descent were identified with hyperpigmentation on their palms. One patient in both the hyperpigmentation and no pigmentation groups were on AZT prior to FTC use.

Comment

The clinical use of FTC – mainly with TDF as fixed-dose combination – and of 3TC mainly with AZT – may affect the findings of cohort analysis.

References:

1. McColl DJ, Lu B, Miller MD et al. Pooled analysis of recent emtricitabine and lamivudine clinical trials reveals differences in rates of development of the M184V/I mutation. 10th European AIDS Conference (EACS), 17-20 November 2005, Dublin, Ireland. Poster PE 7.3/17.
2. Pollock KM, Nelson M. Emtricitabine intolerance in treatment experienced patients switched from Lamivudine; Kobler outpatients Chelsea and Westminster Hospital, London. 10th EACS, Poster 9.1/5
3. Rawlings K, Calderon R, Albert A, et al. The evaluation of palmar freckling in HIV positive patients of African descent at a single center. 10th European AIDS Conference (EACS), 17-20 November 2005, Dublin, Ireland. Poster PE9.1/6.