Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression.
BACKGROUND
Virologic rebound can result from suboptimal antiviral potency in combination antiretroviral therapy.


METHODS
Multicenter, partially blinded, prospective, randomized study of 202 HIV-infected subjects to determine whether therapy intensification improves long-term rates of virologic suppression.


METHODS
Subjects had plasma HIV RNA < 200 copies/ml, CD4 cell count of > 200 x 10(6) cells/l, and treatment with indinavir (IDV) + zidovudine (ZDV) + lamivudine (3TC) for at least 6 months before randomization to stay on this regimen or to receive IDV + didanosine (ddI) + stavudine (d4T) plus or minus hydroxyurea (HU) (600 mg twice daily). Treatment failure was defined as either confirmed rebound of HIV RNA level to > 200 copies/ml or a drug toxicity necessitating treatment discontinuation.


RESULTS
Treatment failure occurred more frequently in subjects randomized to the HU-containing arm (32.4%), than in those taking IDV + ddI + d4T (17.6%) or IDV + ZDV + 3TC (7.6%). The time to treatment failure was shorter for the HU-containing arm compared with the IDV + ZDV + 3TC (P < 0.0001) or IDV + ddI + d4T arms (P = 0.032). Dose-limiting toxicities rather than virologic rebound accounted for the differences between treatment failure among the study arms. Pancreatitis led to treatment discontinuation in 4% of subjects in treatment arms containing ddI + d4T. Three subjects with pancreatitis died, all randomized to the HU-containing arm.


CONCLUSIONS
Switching to IDV + ddI + d4T + HU in patients treated with IDV + ZDV + 3TC was associated with a worse outcome, principally because of drug toxicity.
Havlir
D V
DV
University of California at San Diego and the San Diego Veterans Affairs Healthcare System, San Diego, California 92103, USA.
Gilbert
P B
PB
Bennett
K
K
Collier
A C
AC
Hirsch
M S
MS
Tebas
P
P
Adams
E M
EM
Wheat
L J
LJ
Goodwin
D
D
Schnittman
S
S
Holohan
M K
MK
Richman
D D
DD
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use / Q000633:toxicity*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use / Q000633:toxicity*; D019469:Indinavir / Q000627:therapeutic use / Q000633:toxicity; D019259:Lamivudine / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D010195:Pancreatitis / Q000139:chemically induced / Q000401:mortality; D011446:Prospective Studies; D016019:Survival Analysis; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use / Q000633:toxicity
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D006918:Hydroxyurea