Preliminary 48 week trial data presented to the Barcelona AIDS Conference suggests that a HAART regimen containing the nucleotide analogue tenofovir is just as effective as a traditional dual NRTI backbone at controlling viral load, but is significantly less likely to cause an increase in triglycerides.
The multi-centre, placebo controlled trial has recruited 600 patients with no previous HAART treatment and a viral load above 5000 copies/mL to compare the safety and effectiveness of a regimen containing the nucleotide analogue tenofovir, with the NRTI 3TC and the NNRTI efavirenz, against a regimen containing dual NRTIs (d4T and 3TC) and efavirenz.
At baseline intent to treat analysis, the average viral load across both treatment groups was 81,300 copies/ml and CD4 count was 279 cells/mm3. At 48 weeks, 87% of people in both treatment arms had achieved a viral load below 400 copies/mL and comparable numbers had achieved a viral load below 50 copies/mL (82% of the tenofovir arm and 81% of the d4T arm). There had also been comparable increases in CD4 count, with an average increase of 169 cells/mm3 in those treated with tenofovir and 167 cells/mm3 in the d4T arm. The very high rates of viral suppression seen in the study can in part be explained by the ability of trial participants to switch to nevirapine if they were unable to tolerate efavirenz.
Similar numbers of patients experienced moderately severe or severe side effects in both arms of the trial, however, only 3% of patients in the tenofovir arm experienced mitochondrial related toxicities such as peripheral neuropathy, lipodystrophy and lactic acidosis, against 11% of those treated with d4T. Smaller increases in cholesterol were noted in the tenofovir arm, with an average increase of 0.64mmol/L against 1.37mmol/L. Further, no increases in levels of triglycerides were noted in the tenofovir arm of the trial, however triglycerides increased by an average of 1.91mmol/L in those treated with d4T.
This early data clearly offers encouragement that tenofvoir containing regimens may not be associated with some of the metabolic abnormalities seen in other HAART regimens. Further results from this 144 week trial will be eagerly awaited.
Reference:
Staszewski S et al. Efficacy and safety of tenofovir disoproxil fumarate versus stavudine (d4T) when used in combination with lamivudine (3TC) and efavirenz in HIV-1 infected patients naïve to antiretroviral therapy: 48 week results. Abstract 17, Fourteenth International AIDS Conference, Barcelona 2002.