The overall goal of this proposal remains unchanged and is to investigate the effect of pregnancy on response to highly active antiretroviral therapy (HAART) among HIV-i- women in treatment in Johannesburg, South Africa. In addition, we will continue developing the advanced quantitative epidemiologic methods described in the training component ofthe K99 portion of this grant. Prevalence of HIV among pregnant women in South Africa is substantially higher than that among other adults. Despite extensive study of interventions for the prevention of mother to child transmission of HIV, and response to antiretroviral therapy during and after such interventions, little is known about the effect of pregnancy itself on responses to and retention in therapy. Fully understanding the effect of pregnancy on maternal responses to HAART is essential to providing good clinical care to H1V+ women in Africa and elsewhere. To address these questions, this work proposes to examine the effect of pregnancy on immunologic responses to HAART, clinical (AIDS/death) responses to HAART, and to adherence to HAART and retention in care. Because it is impossible (and highly unethical) to randomize the exposure of pregnancy, this study will rely on high quality clinical data collected in the Themba Lethu Clinic in Johannesburg, South Africa, an urban antiretroviral therapy clinic associated with the Clinical HIV Research Unit at the University ofthe Witwatersrand. The Principal Investigator of the proposed work, Dr. Daniel Westreich, has a strong track record in producing high quality research in collaboration with investigators and clinicians at the Clinic. The analysis of these data will require the use of structural models, an advanced body of epidemiologic methods.

Public Health Relevance

This work will answer a suite of key substantive questions around the impact of pregnancy on response to HAART in South Africa. In doing so, this work will dramatically increase the base of scientific and public health evidence on this important subject, most likely in a way which is generalizable to much of sub-Saharan Africa. In addition, this work and training will continue to develop and establish Dr. Westreich as a health scientist.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Mofenson, Lynne M
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Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
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Westreich, Daniel; Jamal, Naiomi; Smith, Jennifer S et al. (2014) Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa. Contraception 89:286-91
Westreich, Daniel (2014) From exposures to population interventions: pregnancy and response to HIV therapy. Am J Epidemiol 179:797-806
Westreich, Daniel; Greenland, Sander (2013) The table 2 fallacy: presenting and interpreting confounder and modifier coefficients. Am J Epidemiol 177:292-8
Westreich, Daniel; Rosenberg, Molly; Schwartz, Sheree et al. (2013) Representation of women and pregnant women in HIV research: a limited systematic review. PLoS One 8:e73398
Fox, Matthew P; Maskew, Mhairi; MacPhail, A Patrick et al. (2013) Cohort profile: the Themba Lethu Clinical Cohort, Johannesburg, South Africa. Int J Epidemiol 42:430-9
Westreich, Daniel; Maskew, Mhairi; Evans, Denise et al. (2013) Incident pregnancy and time to death or AIDS among HIV-positive women receiving antiretroviral therapy. PLoS One 8:e58117
Hanrahan, Colleen F; Westreich, Daniel; Van Rie, Annelies (2012) Verification bias in a diagnostic accuracy study of symptom screening for tuberculosis in HIV-infected pregnant women. Clin Infect Dis 54:1377-8; author reply 1378-9
Westreich, Daniel; Cole, Stephen R; Schisterman, Enrique F et al. (2012) A simulation study of finite-sample properties of marginal structural Cox proportional hazards models. Stat Med 31:2098-109
Westreich, Daniel; Evans, Denise; Firnhaber, Cindy et al. (2012) Prevalent pregnancy, biological sex, and virologic response to antiretroviral therapy. J Acquir Immune Defic Syndr 60:489-94
Westreich, Daniel; Cole, Stephen R; Young, Jessica G et al. (2012) The parametric g-formula to estimate the effect of highly active antiretroviral therapy on incident AIDS or death. Stat Med 31:2000-9

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