This proposal by the University of North Carolina Project based in Lilongwe, Malawi aims to characterize safety, durability, ART resistance, and clinical outcomes for mothers and infants exposed to the efavirenz-based Option B+ regimen for Prevention of Mother to Child Transmission (PMTCT) and HIV treatment in Malawi. Option B+ is an innovative strategy pioneered within Malawi that provides universal life-long ART (tenofovir/lamivudine/efavirenz: TDF/3TC/EFV) for pregnant and breastfeeding women. Importantly, Option B+ was adopted largely based on programmatic need and has not been directly studied in clinical trials. The safety of a TDF/3TC/EFV based regimen used during pregnancy has not been systematically evaluated. Notably, TDF/3TC/EFV has a low barrier to resistance such that women and infants may be particularly susceptible to resistance in the event of sub- optimal retention or adherence. Hence, the durability of the regimen may be sub- optimal over time and second line therapy may be required for subsequent pregnancies. Now, with over 2 years of follow-up time in the Option B+ program in Malawi, we are in a unique position to explore these questions related to treatment failure, in addition to the effectiveness and safety of second line therapy with Atazanavir/ritonavir among women presenting with subsequent pregnancies in the program. The proposed study will take place at four high volume antenatal sites within Lilongwe, Malawi where UNC project and the Baylor Tingathe Program (who will be collaborating on this study) have established infrastructure. Using a prospective cohort study design, we will enroll newly identified HIV infected women at the first antenatal visi and follow maternal and infant outcomes through year 3 post-delivery. Among women with subsequent pregnancies in the program, we will measure the prevalence of virologic failure and assess the need for second line therapy. In the event of failure, we will evaluate the safety of Atazanavir/ritonavir during pregnancy. Among defaulters of the program with subsequent pregnancies, after resumption of first line therapy, we will evaluate for early treatment failure and determine resistance profiles associated with this population. For all cohorts, key outcomes will include DAIDS grade 3 or 4 events, adverse pregnancy and birth outcomes, HIVRNA suppression, maternal and infant drug resistance, and infant neurologic development. Our research plan has been carefully developed to be complementary to existing program and research activities and anticipates the next critical questions that can only be answered with a more mature Option B+ program. Hence, our ability to answer these questions now will inform other programs as they embark on an Option B+ program.

Public Health Relevance

Option B+ is an innovative strategy pioneered within Malawi that provides universal life- long ART (tenofovir/lamivudine/efavirenz: TDF/3TC/EFV) for pregnant and breastfeeding women to promote maternal health and prevent HIV transmission to infants. The safety of a TDF/3TC/EFV based regimen used during pregnancy has not been systematically evaluated. The drug combination of TDF/3TC/EFV may develop HIV resistance easily if the women do not adhere to the medication and second line treatment may be required for subsequent pregnancies. Like the first line regimen, the safety of the second line treatment using Atazanavir/ritonavir during pregnancy has not be critically evaluated. The proposed study will take place at four high volume antenatal sites within Lilongwe, Malawi where UNC project and the Baylor Tingathe Program have established infrastructure. We will enroll newly identified HIV infected women at the first antenatal visit and follow maternal and infant outcomes through year 3 post-delivery. Additionally, we will measure the prevalence of treatment failure among women on ART presenting with subsequent pregnancies to assess the need for second line therapy. In the event of treatment failure, we will evaluate the safety of Atazanavir/ritonavir during pregnancy. Among defaulters of the program presenting with subsequent pregnancies, after resumption of first line therapy, we will evaluate for early treatment failure and determine resistance profiles associated with this population. For all groups, we will evaluate clinical events, adverse pregnancy and birth outcomes, and successful suppression of HIV virus, maternal drug resistance, and infant neurologic development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD080485-03
Application #
9065981
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Chakhtoura, Nahida Abdo
Project Start
2014-06-14
Project End
2020-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Harrington, Bryna J; Hosseinipour, Mina C; Maliwichi, Madalitso et al. (2018) Prevalence and incidence of probable perinatal depression among women enrolled in Option B+ antenatal HIV care in Malawi. J Affect Disord 239:115-122
Hauser, Blake M; Miller, William C; Tweya, Hannock et al. (2018) Assessing Option B+ retention and infant follow-up in Lilongwe, Malawi. Int J STD AIDS 29:185-194
Harrington, Bryna J; Pence, Brian W; John, Mathias et al. (2018) Prevalence and factors associated with antenatal depressive symptoms among women enrolled in Option B+ antenatal HIV care in Malawi: a cross-sectional analysis. J Ment Health :1-8
Rosenberg, Nora E; Graybill, Lauren A; Wesevich, Austin et al. (2018) Individual, Partner, and Couple Predictors of HIV Infection among Pregnant Women in Malawi: A Case-Control Study. AIDS Behav 22:1775-1786
Chagomerana, Maganizo B; Miller, William C; Tang, Jennifer H et al. (2018) Optimizing prevention of HIV mother to child transmission: Duration of antiretroviral therapy and viral suppression at delivery among pregnant Malawian women. PLoS One 13:e0195033
Wesevich, Austin; Mtande, Tiwonge; Saidi, Friday et al. (2017) Role of male partner involvement in ART retention and adherence in Malawi's Option B+ program. AIDS Care 29:1417-1425
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Chagomerana, Maganizo B; Miller, William C; Pence, Brian W et al. (2017) PMTCT Option B+ Does Not Increase Preterm Birth Risk and May Prevent Extreme Prematurity: A Retrospective Cohort Study in Malawi. J Acquir Immune Defic Syndr 74:367-374
O'Shea, Michele S; Rosenberg, Nora E; Tang, Jennifer H et al. (2016) Reproductive intentions and family planning practices of pregnant HIV-infected Malawian women on antiretroviral therapy. AIDS Care 28:1027-34