Abacavir, Efavirenz and Didanosine, with or without Hydroxyurea, in HIV-infected Adults Failing Initial Nucleoside/Protease Inhibitor-containing Regimens

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Hydroxyurea (HU) is an immunomodulatory agent that has been documented to enhance the antiretroviral activity of nucleoside reverse transcriptase inhibitors (NRTIs), such as abacavir/ ABC (Ziagen) and didanosine/ ddI (Videx), and would be expected to improve virologic efficacy.

A 48-week, phase IV, multicenter, open-label, proof-of-concept clinical trial was conducted to evaluate second-line, protease inhibitor (PI)-sparing therapy with ABC/efavirenz/ EFV (Sustiva)/ddI plus HU or without HU in HIV-infected patients failing to achieve HIV-1 RNA 400 copies/mL or less after at least 16 weeks of treatment with lamivudine/zidovudine (Epivir/Retrovir) or lamivudine/stavudine (Zerit), plus 1 or 2 PIs.

Patients were assigned to ABC (300 mg twice daily)/ EFV (600 mg once daily)/ ddI 400 mg once daily plus HU 500 mg twice daily (n=30) or this regimen without HU (n=24).

Results

· Baseline mean HIV-1 RNA-1 was 3.86 log10 copies/mL and CD4+ cell count was 345 cells/mm3.

· A similar percentage of patients in the non-HU arm (58%) and HU arm (53%) completed the study.

· Intent-to-treat: missing = failure analysis showed no differences in proportions of patients in the non-HU and HU arms achieving undetectable plasma HIV-1 RNA levels at week 24 (<400 copies/mL: 58% [14/24] vs 57% [17/30], P = 0.899; <50 copies/mL (50% [12/24] vs 47% [14/30], P = 0.780).

· Median change from baseline in CD4+ cell count in the non-HU and HU arms at week 48 was +114 cells/mm3 and -63 cells/mm3 (P = 0.007), respectively.

· Both regimens were generally well tolerated, although more patients in the HU arm withdrew prematurely from the study due to adverse events (23% vs 4%).

· Four cases of possible ABC-related hypersensitivity were observed.

Conclusions

Based on these findings, the authors conclude, “ABC/EFV/ddI was an effective and well-tolerated second-line regimen for nucleoside/PI-experienced HIV-infected patients.”

“The addition of HU blunted the CD4+ cell response, did not appear to enhance antiviral activity, and resulted in more treatment-limiting adverse events.”

04/20/05

Reference
S Swindells and others. Abacavir, efavirenz, didanosine, with or without hydroxyurea, in HIV-infected adults failing initial nucleoside/protease inhibitor-containing regimens. BioMed Central Infectious Diseases 5(1): 23. April 8, 2005 [Epub ahead of print]