Abacavir, efavirenz, didanosine, with or without hydroxyurea, in HIV-infected adults failing initial nucleoside/protease inhibitor-containing regimens.
BACKGROUND
Hydroxyurea (HU) is an immunomodulatory agent that has been documented to enhance the antiretroviral activity of nucleoside reverse transcriptase inhibitors, such as abacavir (ABC) and didanosine (ddI), and would be expected to improve virologic efficacy.


METHODS
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)/ddI plus HU or without HU in HIV-infected subjects failing to achieve HIV-1 RNA < or = 400 copies/mL after > or = 16 weeks of treatment with lamivudine/zidovudine or lamivudine/stavudine, plus 1 or 2 PIs. Subjects 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 was 3.86 log10 copies/mL and CD4+ cell count was 345 cells/mm3. A similar percentage of subjects 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 subjects 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 subjects 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
ABC/EFV/ddI was an effective and well-tolerated second-line regimen for nucleoside/PI-experienced HIV-infected subjects. The addition of HU blunted the CD4+ cell response, did not appear to enhance antiviral activity, and resulted in more treatment-limiting adverse events.
Swindells
Susan
S
HIV Clinic, University of Nebraska Medical Center, Omaha, NE, USA. sswindells@unmc.edu
Cohen
Calvin J
CJ
Berger
Daniel S
DS
Tashima
Karen T
KT
Liao
Qiming
Q
Pobiner
Bonnie F
BF
Snidow
Jerry W
JW
Pakes
Gary E
GE
Hernandez
Jaime E
JE
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D016049:Didanosine / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D017211:Treatment Failure; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D016049:Didanosine; D015224:Dideoxynucleosides; D006918:Hydroxyurea; D010078:Oxazines; D012367:RNA, Viral; D000099227:Abacavir; C098320:efavirenz