Peripartum nevirapine (NVP) is an important and effective intervention for perinatal HIV prevention in resource-constrained settings. This simple regimen substantially reduces mother-to-child transmission of the virus when used alone or in combination with other antiretroviral drugs. Numerous studies, however, have demonstrated significant viral drug resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of drugs (of which NVP is a part) in the weeks following ingestion of the single maternal dose. Although these resistance mutations appear transient by standard assays, resistant virus could become latent, and only later compromise treatment response when women start antiretroviral therapy. In Dr. Chi's original IRSDA, he conducted a randomized trial of adjuvant single-dose tenofovir (TDF, SOOmg) / emtricitabine (FTC, 200mg) to reduce postpartum NNRTI resistance. The intervention was associated with a 73% reduction in drug resistance at two weeks postpartum (RR = 0.27, 95%CI = 0.11, 0.66) and a 53% reduction at six weeks (RR = 0.47, 95%CI = 0.29, 0.77). Although effective, in absolute terms, a significant proportion of women (12%) still developed NNRTI resistance with the intervention. This is concerning because peripartum NVP remains an integral part of PMTCT for the majority of HIV-infected women worldwide. For his IRSDA renewal, Dr. Chi proposes a follow-up clinical trial to investigate optimized dosing of the TDF/FTC regimen. He will compare the single-dose intrapartum TDF/FTC (SOOmg / 200mg) regimen with a two-dose regimen of TDF/FTC (GOOmg MOOmg), taken in labor and upon discharge from the delivery ward. Dr. Chi hypothesizes that this enhanced adjuvant regimen will significantly reduce postpartum NNRTI resistance at 6 weeks postpartum, from 12% to 3%. Alongside this primary project, Dr. Chi will continue to work closely with his mentors to solidify his expertise in obstetrics, HIV medicine, and international health. He will build proficiency in other research methodologies such as cost-effectiveness analysis, survey studies, and cohort analysis. The ultimate goal of this renewal will be Dr. Chi's development into an independently funded research scientist, so that he may continue to investigate important and relevant research questions for resource-constrained settings such as Zambia.

Public Health Relevance

Although single-dose nevirapine is simple and effective for perinatal HIV prevention, its use can lead to the development of drug-resistant viral strains. In this grant, Dr. Chi is investigating a novel method to reduce the development of this drug resistance. If effective, this intervention could have an immediate impact in settings where single-dose nevirapine is used, and potentially improve the long-term health outcomes among HIV-infected women and their children.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
2K01TW006670-05
Application #
7558330
Study Section
Special Emphasis Panel (ZRG1-BDA-K (50))
Program Officer
Jessup, Christine
Project Start
2003-12-01
Project End
2010-07-31
Budget Start
2009-02-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$105,586
Indirect Cost
Name
University of Alabama Birmingham
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Rathod, Sujit D; Chi, Benjamin H; Kusanthan, Thankian et al. (2014) Trends in all-cause mortality during the scale-up of an antiretroviral therapy programme: a cross-sectional study in Lusaka, Zambia. Bull World Health Organ 92:734-41
Stringer, Jeffrey S A; Mwango, Albert J; Giganti, Mark J et al. (2012) Effectiveness of generic and proprietary first-line anti-retroviral regimens in a primary health care setting in Lusaka, Zambia: a cohort study. Int J Epidemiol 41:448-59
Turnbull, Eleanor; Lembalemba, Mwila K; Guffey, M Brad et al. (2011) Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments. Trop Med Int Health 16:894-901
Chi, Benjamin H; Vwalika, Bellington; Killam, William P et al. (2011) Implementation of the Zambia electronic perinatal record system for comprehensive prenatal and delivery care. Int J Gynaecol Obstet 113:131-6
Dorton, B J; Mulindwa, J; Li, M S et al. (2011) CD4+ cell count and risk for antiretroviral drug resistance among women using peripartum nevirapine for perinatal HIV prevention. BJOG 118:495-9
Koethe, John R; Limbada, Mohammed I; Giganti, Mark J et al. (2010) Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia. AIDS 24:2117-21
Chi, Benjamin H; Cantrell, Ronald A; Mwango, Albert et al. (2010) An empirical approach to defining loss to follow-up among patients enrolled in antiretroviral treatment programs. Am J Epidemiol 171:924-31
Koethe, John R; Heimburger, Douglas C (2010) Nutritional aspects of HIV-associated wasting in sub-Saharan Africa. Am J Clin Nutr 91:1138S-1142S
Giganti, Mark J; Levy, Jens W; Banda, Yolan et al. (2010) Methods and baseline results of a repeated cross-sectional survey to assess the public health impact of antiretroviral therapy in Lusaka, Zambia. Am J Trop Med Hyg 82:971-7
Chi, Benjamin H; Mwango, Albert; Giganti, Mark et al. (2010) Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia. J Acquir Immune Defic Syndr 54:63-70

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