Abacavir alters the transcription of inflammatory cytokines in virologically suppressed, HIV-infected women.
BACKGROUND
Abacavir (ABC) may be associated with a small, increased risk of myocardial infarction in HIV-infected adults, possibly related to cytokine-mediated inflammation.


METHODS
To evaluate the induction of inflammatory cytokine transcription by ABC, we used samples from women randomized to receive zidovudine/lamivudine/ABC (Trizivir) or lopinavir/ritonavir and zidovudine/lamividine (Kaletra/Combivir) from the third trimester through six-months postpartum for the prevention of mother-to-child transmission (PMTCT). Women were matched by CD4 count and baseline HIV RNA. All women attained viral suppression (<50 copies/ml) by the time of sampling.


RESULTS
Four cytokines showed a difference in expression between the treatment arms, all in a proinflammatory direction for the ABC arm: CD40LG 1.82-fold, (p=.027); IL-8 3.16-fold (p=.020); LTA 2.82-fold, (p=.008); and CCL5 -1.67-fold, (p=.035). At 12-months postpartum, 6-months after antiretroviral discontinuation, cytokine expression was similar by treatment arm.


CONCLUSIONS
We conclude that ABC may upregulate proinflammatory cytokines at the transcriptional level in this population.
Harvard School of Public Health AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Iain J
IJ
MacLeod
Christopher F
CF
Rowley
Shahin
S
Lockman
Anthony
A
Ogwu
Sikhulile
S
Moyo
Erik
E
van Widenfelt
Mompati
M
Mmalane
Joseph
J
Makhema
M
M
Essex
Roger L
RL
Shapiro
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000096:biosynthesis*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006678:HIV / Q000302:isolation & purification; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D014158:Transcription, Genetic / Q000187:drug effects*; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D016207:Cytokines; D015224:Dideoxynucleosides; D007155:Immunologic Factors; D000099227:Abacavir