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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

Powis, Kathleen M. MD, MPH*,†,‡,§; McElrath, Thomas F. MD; Hughes, Michael D. PhD; Ogwu, Anthony MB, BS§; Souda, Sajini MBBS, MD, DTM&H#; Datwyler, Saul A. PhD**; von Widenfelt, Erik BS§; Moyo, Sikhulile MS, MPH§; Nádas, Marisa MD, MPH††; Makhema, Joseph MB, ChB, MRCB§; Machakaire, Esther MBChB, MPH‡‡; Lockman, Shahin MD, MS‡,§,§§; Essex, Max DVM, PhD‡,§; Shapiro, Roger L. MD, MPH‡,§,‖‖

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15th, 2013 - Volume 62 - Issue 5 - p 517–524
doi: 10.1097/QAI.0b013e318286d77e
Clinical Science

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.

Departments of *Internal Medicine;

Pediatrics, Massachusetts General Hospital, Boston, MA;

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA;

§Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana;

Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Boston, MA;

Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA;

#University of Botswana School of Medicine, Gaborone, Botswana;

**Abbott Laboratories, Abbott Park, IL;

††Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA;

‡‡Centers for Disease Control-Botswana, Gaborone, Botswana;

§§Infectious Disease Unit, Brigham and Women's Hospital, Boston, MA; and

‖‖Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA.

Correspondence to: Kathleen M. Powis, MD, MPH, 100 Cambridge St, 15th floor, Boston, MA 02114 (e-mail:

Presented in part at the 19th Conference on Retroviruses and Opportunistic Infections, March 5–8, 2012, Seattle, WA.

M.H. has served as a paid member of the Data Survey and Monitoring Board for Beohringer Ingelheim, Pfizer, Tibotec, and Medicines Development.

Supported by a grant (U01-AI066454) from the National Institute of Allergy and Infectious Diseases. Funding support from Brigham and Women's Global Women's Health Fellowship supported K.M.P.'s salary during the Mma Bana study and M.N.'s salary during manuscript preparation. K.M.P. received salary support from Harvard University Center for AIDS Research grant (P30 AI060354) and National Institute of Child Health and Human Development grant (1K23HD070774-01A1) during the period of manuscript preparation. The Fogarty AITRP grant (D43 TW000004) provided funding for A.O. and S.M. Mma Bana study drugs were provided by Abbott Pharmaceuticals, GlaxoSmithKline, and the government of Botswana.

Received July 17, 2012

Accepted January 08, 2013

© 2013 Lippincott Williams & Wilkins, Inc.