A regimen of tenofovir (Viread) and AZT (zidovudine) / 3TC (lamivudine) / abacavir (Trizivir) appears to be an effective and well tolerated second-line regimen in individuals who have experienced early treatment failure with either an non-nucleoside-based or protease inhibitor-based initial combination, according to research presented to the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington. A paper separately presented to the conference has shown that tenofovir and Trizivir is comparable to efavirenz (Sustiva) and AZT / 3TC (Combivir) in first-line treatment.
A total of 51 patients who had experienced treatment failure after taking an initial highly-active antiretroviral therapy (HAART) regimen of AZT (or d4T [stavudine, Zerit]), 3TC and a protease inhibitor or a non-nucleoside were treated with twice daily Trizivir, and once-daily tenofovir. The study is described by the investigators as the Ziagen Intensification Protocol (ZIP) although it involves the discontinuation of one drug class and substitution of tenofovir.
To be included in the study patients were required to have a viral load between 400 and 1000 copies/ml and a CD4 cell count above 100 cells/mm3. Individuals were excluded from entry if a genotypic resistance test showed two nucleoside analogue reverse transcriptase inhibitor (NRTI) resistance mutations or the K65R mutation. The study is intended to last 48 weeks.
Investigators presented interim 24-week data.
At baseline, the median viral load was 1970 copies/ml, and median CD4 cell count was 436 cells/mm3. In total 43 patients (84%) completed 24 weeks of follow-up.
Using an intent-to-treat analysis, investigators established that 75% of individuals had a viral load below 400 copies/ml at week 24. The less rigorous on-treatment analysis showed that 93% of patients had a viral load below 400 copies/ml. Again using an intent-to-treat analysis, the investigators found that 65% of patients had a viral load below 50 copies/ml, with 80% being below 50 copies/ml using an on-treatment analysis.
At the time of the interim analysis, there were no cases of confirmed virological failure or of hypersensitivity to abacavir. Virological failure was defined as failure to achieve a viral load below 400 copies/ml or a 0.5log10 rebound above 400 copies/ml (to 1265 copies/ml).
Two patients discontinued treatment because of nausea and another patient because of fatigue. Nausea, vomiting, fatigue, headache, bronchitis and insomnia were each experienced by 10% or more of patients.
On the basis of this interim analysis, the investigators conclude that a regimen of twice-daily Trizivir and once-daily tenofovir is an effective and well-tolerated treatment for patients who experienced early treatment failure with AZT (or d4T), 3TC and a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor. In addition, the investigators believe that the use of the tenofovir and Trizivir regimen “following failure on a protease inhibitor or NNRTI-based regimen may preserve future treatment options with other classes of antiretrovirals.”
Rodriguez AE et al. Abacavir/lamivudine/zidovudine and tenofovir in subjects with early virologic failure on an initial regimen of zidovudine or stavudine and lamivudine and a protease inhibitor or non-nucleoside reverse transcriptase inhibitor (ESS3005, ZIP). 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract H-563, 2004.