Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine.
OBJECTIVE
To determine the effect of adjuvant prednisolone use on the development of abacavir (ABC)- and nevirapine (NVP)-associated hypersensitivity reactions (HSR).


METHODS
Randomized open-label study in antiretroviral-naive adult HIV-1 infected patients using a factorial design in which NVP and/or hydroxyurea (HU) and/or prednisolone are added to a regimen of ABC, zidovudine and lamivudine. Prednisolone (40 mg once daily) was added for the first 2 weeks of treatment. As it was difficult to distinguish ABC-associated HSR from NVP-associated HSR, these events were treated as a composite endpoint. The odds ratio (OR) of developing HSR for prednisolone-use was calculated with and without stratification by NVP and/or HU. Logistic regression was performed to identify risk factors for developing HSR.


RESULTS
Of the 229 patients 115 were randomized to prednisolone and 114 to no-prednisolone; 19 (17%) and 11 (10%) patients, respectively, developed HSR. The expected prevention of HSR by prednisolone use was not observed. In fact use of prednisolone showed an increased risk for HSR although this did not reach statistical significance [OR, 1.82; 95% confidence interval (CI), 0.82-4.03]. There was a higher incidence of HSR in the NVP group than in the non-NVP group (20% versus 6%; P = 0.002). An additional risk factor identified in a multivariate logistic model was a high baseline CD4 cell count (OR, 1.26 per 100 x 10(6) cells/l increase; 95% CI, 1.06-1.51).


CONCLUSIONS
The simultaneous start of ABC and NVP in first-line antiretroviral regimens should be avoided because of a high (20%) incidence of HSR. Short-term therapy with prednisolone did not prevent HSR in patients using ABC with or without NVP.
Wit
F W
FW
International Antiviral Therapy Evaluation Center, Department of Human Retrovirology and Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Wood
R
R
Horban
A
A
Beniowski
M
M
Schmidt
R E
RE
Gray
G
G
Lazzarin
A
A
Lafeuillade
A
A
Paes
D
D
Carlier
H
H
van Weert
L
L
de Vries
C
C
van Leeuwen
R
R
Lange
J M
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000517:prevention & control*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
D019380:Anti-HIV Agents; D000893:Anti-Inflammatory Agents; D015224:Dideoxynucleosides; D019829:Nevirapine; D011239:Prednisolone; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir