High viral load and elevated angiogenic markers associated with increased risk of preeclampsia among women initiating highly active antiretroviral therapy in pregnancy in the Mma Bana study, Botswana.
BACKGROUND
Risk factors associated with preeclampsia in HIV-infected women remain largely unknown. Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women, but changes in angiogenic markers after highly active antiretroviral therapy (HAART) initiation have not been studied.


METHODS
The Mma Bana study randomized 560 HIV-infected, HAART-naive pregnant women with CD4 counts ≥ 200 cells per cubic millimeter between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine. Another 170 participants with CD4 counts less than 200 cells per cubic millimeter initiated nevirapine/zidovudine/lamivudine between 18 and 34 weeks gestation. Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered using logistic regression. Plasma samples drawn at HAART initiation and 1 month later from 60 women without preeclampsia and at HAART initiation for all 11 preeclamptic women were assayed for placental growth factor (PlGF) and soluble FMS toll-like tyrosine kinase-1 (sFlt-1).


RESULTS
Pre-HAART viral load greater than 100,000 copies per milliliter was associated with preeclampsia (odds ratio: 5.8, 95% confidence interval: 1.8 to 19.4, P = 0.004). Median pre-HAART PlGF level was lower and sFlt-1 was higher in women who developed preeclampsia vs those who did not (130 vs 992 pg/mL, P = 0.001; 17.5 vs 9.4 pg/mL, P = 0.03, respectively). In multivariate analysis, PlGF and viral load remained significantly associated with preeclampsia. No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women.


CONCLUSIONS
Pre-HAART viral load greater than 100,000 copies per milliliter and PlGF predicted preeclampsia among women starting HAART in pregnancy. Among non-preeclamptic women, HAART treatment did not significantly alter levels of PlGF or sFlt-1 after 1 month of treatment.
Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. kpowis@partners.org
Kathleen M
KM
Powis
Thomas F
TF
McElrath
Michael D
MD
Hughes
Anthony
A
Ogwu
Sajini
S
Souda
Saul A
SA
Datwyler
Erik
E
von Widenfelt
Sikhulile
S
Moyo
Marisa
M
Nádas
Joseph
J
Makhema
Esther
E
Machakaire
Shahin
S
Lockman
Max
M
Essex
Roger L
RL
Shapiro
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001902:Botswana; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development* / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000139:chemically induced / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D011257:Pregnancy Proteins / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1