Switch from zidovudine- to non-zidovudine-containing regimens is associated with modest haematological improvement and no obvious clinical benefit: a substudy of the ANRS 099 ALIZE trial

Abstract

Background: Zidovudine, the first antiretroviral agent, has short-term haematological toxicity. However, it is unclear whether patients tolerating long-term zidovudine-containing regimens will benefit from a switch to non-zidovudine-containing regimens.Methods: One hundred and fifty-eight patients enrolled in the ALIZE trial receiving zidovudine at baseline were analysed. These patients were randomized to continue their regimen or to switch to a combination of emtricitabine, didanosine and efavirenz for 48 weeks. Changes from baseline in haemoglobin (Hb), neutrophil and platelet counts were compared between arms as well as the occurrence of cardiovascular events, bacterial infections, use of haematopoietic growth factors, blood transfusion and quality of life using the Medical Outcome Study HIV (MOS-HIV) health survey.Results: Eighty-one patients continued their regimen and 77 switched. At 48 weeks, mean change from baseline in Hb were 10.73 and 20.37 g/dL in the switch and maintenance groups, respectively (P < 0.01). Mean neutrophil counts increased by 592 and 51 cells/mm 3 in the switch and maintenance groups, respectively (P 5 0.02). The occurrence of cardiovascular events or bacterial infections was similar in both treatment arms with no use of haematopoietic growth factors or blood transfusion. Also, mean change from baseline in MOS-HIV physical and mental health summary scores was similar in both arms. Conclusions:A switch from a long-standing zidovudine-to a non-zidovudine-containing regimen modestly improves haematological parameters and is not associated with obvious clinical benefit.

Combination Nucleoside/Nucleotide Reverse Transcriptase Inhibitors for Treatment of HIV Infection

“…The Simplification With Easier Emtricitabine and Tenofovir (SWEET) study demonstrated reduced incidence of anemia and improved lipid parameters after switching from ZDV/3TC to TDF/FTC 54 . Other studies have also demonstrated similar results 55,56 . Preliminary evidence from Thailand suggests that treatment-limiting toxicity associated with ZDV can be reduced without compromising efficacy if administered at the reduced dose of 200 mg twice daily 57 .…”

Responsiveness of the MOS-HIV and EQ-5D in HIV-infected adults receiving antiretroviral therapies

“…Of all MOS-HIV domains measured, only one significant difference between groups was observed; compared to CPI/r, TPV/r was associated with a small but significant improvement in pain scores (+4.8 points; P <0.05). A study by Lafaurie et al (2008) [15] evaluated HIV-infected adults receiving a PI-containing ARV regimen and compared maintenance of the current PI-containing regimen versus switch to a once-daily NNRTI-based regimen of EFV/ddI/emtricitabine (FTC). Although a medium effect was observed in the PHS score in the switch arm (mean change −1.76, effect size 0.53), the difference in change from baseline to 48 weeks in both PHS and MHS scores was not statistically significant between treatment groups ( P =0.57 and P =0.42, respectively).…”

Discontinuation of Initial Antiretroviral Therapy in Clinical Practice

“…Switch from zidovudine was associated with significant improvements in hemoglobin level and neutrophil counts parameters. 42 Also, switch from a thymidine analog to TDF leads to significant improvement in limb fat mass, metabolic parameters, and mitochondrial toxicity. 43 – 46 …”