HIV is the leading cause of death among adults aged 15-64 in Africa. Recent wide-spread introduction of highly active antiretroviral therapy (HAART) to treat HIV in Africa has reduced mortality;however, mortality rates remain higher than in industrialized countries. In industrialized countries, HAART has lead to a shift in causes of death from acute opportunistic infections to chronic diseases. Causes of mortality on HAART and changes in specific risks over duration from HAART initiation are unknown in Africa. The proposed study will determine incidence and risks for mortality during HAART, changing factors associated with death over time, specific causes of death, and the role of both TB and hepatitis B in causal pathways to death. This data will be used to model the independent contributions of specific exposures such as HIV viremia, CD4 count, missed visits, and self initiated treatment interruption on death. These data will help to inform public health decisions regarding optimization of care guidelines and to prioritize potential interventions to reduce mortality. The proposed research will be conducted retrospectively within an ART cohort based in company HIV clinics in South Africa. The research will utilize 8 years of prospective follow-up in the ART cohort and routinely obtained autopsies, obtained for approximately 50% of workers who die. Marginal structural models will be used to assess causal inference for time varying covariates and effect modification will be assessed to identifying changing risks for death over time on HAART. This work builds on the PIs experience with research in Africa, longitudinal data analysis, and HIV outcomes. Completing this research in South Africa, along with structured mentorship and advanced statistics courses, will provide the necessary experience and guidance to develop skills and techniques needed for the PI to emerge as an independent investigator in the area of international HIV treatment. Careful description of long-term HAART outcomes and identification of risks for and causes of death is important to optimize treatment algorithms, develop prevention strategies, and implement cost-effective HIV care in Africa. Because of limited resources implementing a level of care as exists in industrialized countries is not feasible in most of Africa. However, the optimum approach to allocating resources to maximize outcomes is currently unclear. Knowledge of risks for and causes of mortality can contribute to informing resource allocation aimed at improving health and survival.

Public Health Relevance

Careful description of long-term HAART outcomes and identification of risks for and causes of death is important to optimize treatment algorithms, develop prevention strategies, and implement cost-effective HIV care in Africa. Because of limited resources implementing a level of care as exists in industrialized countries is not feasible in most of Africa. However, the optimum approach to allocating resources to maximize outcomes is currently unclear. Knowledge of risks for and causes of mortality can contribute to informing resource allocation aimed at improving health and survival.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI083099-04
Application #
8479308
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Huebner, Robin E
Project Start
2010-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$134,325
Indirect Cost
$9,950
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Hoffmann, Christopher J; Mashabela, Fildah; Cohn, Silvia et al. (2014) Maternal hepatitis B and infant infection among pregnant women living with HIV in South Africa. J Int AIDS Soc 17:18871
Hoffmann, Christopher J; Chaisson, Richard E; Martinson, Neil A (2014) Cotrimoxazole prophylaxis and tuberculosis risk among people living with HIV. PLoS One 9:e83750
Hoffmann, Christopher J; Charalambous, Salome; Grant, Alison D et al. (2014) Durable HIV RNA resuppression after virologic failure while remaining on a first-line regimen: a cohort study. Trop Med Int Health 19:236-9
Mabuto, Tonderai; Latka, Mary H; Kuwane, Bulelani et al. (2014) Four models of HIV counseling and testing: utilization and test results in South Africa. PLoS One 9:e102267
Johnson, Leigh F; Mossong, Joel; Dorrington, Rob E et al. (2013) Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies. PLoS Med 10:e1001418
Schomaker, Michael; Egger, Matthias; Maskew, Mhairi et al. (2013) Immune recovery after starting ART in HIV-infected patients presenting and not presenting with tuberculosis in South Africa. J Acquir Immune Defic Syndr 63:142-5
Hoffmann, Christopher J; Lewis, James J; Dowdy, David W et al. (2013) Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model. J Acquir Immune Defic Syndr 63:105-11
Hoffmann, Christopher J; Variava, Ebrahim; Rakgokong, Modiehi et al. (2013) High prevalence of pulmonary tuberculosis but low sensitivity of symptom screening among HIV-infected pregnant women in South Africa. PLoS One 8:e62211
Velen, Kavindhran; Lewis, James J; Charalambous, Salome et al. (2013) Comparison of tenofovir, zidovudine, or stavudine as part of first-line antiretroviral therapy in a resource-limited-setting: a cohort study. PLoS One 8:e64459
Innes, Craig; Hamilton, Robin; Hoffmann, Christopher J et al. (2012) A novel HIV treatment model using private practitioners in South Africa. Sex Transm Infect 88:136-40

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