ICAAC: Tolerability key to superior showing of tenofovir/FTC in head to head match with Combivir

A head-to-head comparison of tenofovir (Viread) / FTC (emtricitabine, Emtriva) with AZT (zidovudine) / 3TC (lamivudine, Combivir) shows that after the first 24 weeks of treatment, patients randomised to the tenofovir group were more likely to have undetectable viral load, apparently due to treatment discontinuations in the Combivir group as a result of poorer tolerability.

Professor Brian Gazzard of the Chelsea and Westminster Hospital, London, presented 24-week interim data from Gilead 934, a randomised comparison of AZT / 3TC / efavirenz (Sustiva) and tenofovir / FTC / efavirenz. The study compared the once daily regimen of tenofovir / FTC / efavirenz (with tenofovir and FTC dosed as separate tablets, not the coformulation of Truvada) with twice daily dosing of AZT / 3TC as Combivir plus efavirenz once daily. Combivir / efavirenz is the most commonly prescribed first-line regimen in the United Kingdom and is also a popular first-line regimen in the United States.

The 934 study recruited 517 treatment-naïve patients with viral loads above 10,000 copies/ml. The median baseline viral load in both groups was 100,000 copies/ml, and median CD4 cell counts were 233 cells/mm³ in the tenofovir / FTC group and 241 cells/mm³ in the Combivir group. The study population provided a good reflection of patients now beginning therapy in all respects except gender (14% of the tenofovir group and 13% of the Combivir group were women).

By week 24, 11% of patients randomised to the tenofovir group and 21% of patients randomised to the Combivir group had discontinued treatment. Patients randomised to Combivir were significantly more likely to discontinue therapy due to adverse events (9 vs. 3%, p = 0.003). Eight patients in the tenofovir group withdrew, two due to non-nucleoside reverse transcriptase inhibitor (NNRTI)-related rash, one due to nausea and five for unspecified adverse reactions. In the Combivir group, 22 patients discontinued due to adverse events, 14 due to anaemia, two due to neutropenia, four due to nausea, three due to fatigue and three due to vomiting.

Patients who discontinued treatment due to anaemia had baseline haemoglobin of 13.8g/dl and baseline haematocrit of 40%. After commencing treatment haemoglobin and haematocrit fell to a low of 6.9mg/dl and 22% respectively.

By intent-to-treat analysis, 87% of tenofovir-treated patients had viral loads below 400 copies/ml and 73% had viral loads below 50 copies/ml. In the Combivir arm, 78% of patients had viral load below 400 copies/ml and 65% had viral load below 50 copies/ml. The differences in both measures were statistically significant (below 400 copies/ml, p = 0.019; below 50 copies/ml, p = 0.038). Changes in CD4 cell count were not significantly different between the two study arms (tenofovir +129 cells/mm³, Combivir +111 cells/mm³).

Patients with viral load above 400 copies/ml at week 24 together with those who discontinued treatment due to virologic rebound above 400 copies/ml prior to week 24 were analysed for resistance mutations. No thymidine analogue mutations were detected in the Combivir group, and no K65R mutations were detected in the tenofovir group. Five tenofovir-treated patients and three Combivir-treated patients had wild type virus. Efavirenz resistance was present in three tenofovir-treated patients and four Combivir-treated patients, while two tenofovir-treated patients and one Combivir-treated patient had resistance to efavirenz and the M184V mutation associated with resistance to 3TC or FTC.

Although tenofovir has been associated with renal problems in treatment-experienced patients, the only patients to experience creatinine elevations were two patients in the Combivir group who developed mild elevations (less than 3.0mg/dl).

Study 934 will continue for a further 24 weeks.