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Dr. Shisana was later appointed on a two year contract (July 1998-July 2000) as Executive Director, Family and Community Health cluster in WHO, which oversaw HIV/AIDS, Reproductive Health and Research, Women's Health and Child and Adolescent Health and Development. One of her biggest accomplishment at the WHO was the establishment of the HIV/AIDS Initiative which includes 23 Departments at the WHO headquarters and six regional offices. Another major accomplishment was her role in spearheading the development and successful adoption of a an HIV/AIDS resolution passed by the World Health Assembly (WHA) (191 countries), the first World Health Assembly (WHA) HIV/AIDS resolution to be passed since 1992. She is a founding member of the International Partnership on HIV/AIDS in Africa and participated in the development of the health sector's response of this partnership. She participated in crucial meetings on HIV/AIDS, including the one organized by the US White House.

Currently, Dr. Shisana is involved in projects on HIV/AIDS in South Africa as principal investigator or co-investigator. In 2000, under her leadership, the National School of Public Health and the HSRC received a grant from the South African Department of Health with a supplement from the CDC to study the impact of HIV/AIDS on the health sector. The objectives were to; a) determine HIV/AIDS-related morbidity and mortality of health professionals; b) estimate morbidity and mortality of patients and determine their demographic profile; c) determine the services that are most severely affected by HIV/AIDS; d) determine impact of HIV/AIDS on human resources; and e) estimate the cost of a program to reduce transmission of HIV from mother to child. These objectives were achieved through a combination of three methods; 1) administration of questionnaires to a national sample of public health facilities to health professionals, patients and administrators; b) analysis of mortality data based on the Death Notification Forms; and c) analysis of mother to child transmission program in the Western Cape.

In 2000, Dr. Shisana received a grant from the South Africa Department of Health to compile a report on the status of HIV/AIDS in South Africa as at the end of 2000. The Department of Health regularly conducts a survey among women attending antenatal clinics. This is one of the main sources of information on the epidemic in South Africa and it forms the cornerstone of the understanding of the spread of the HIV virus in South Africa. The report was completed and submitted to the Department of Health in February, 2002.

Dr. Shisana also received a grant in 2001 from the W.K. Kellogg Foundation to assess the HIV/AIDS situation in Southern Africa. The objectives of the study are to (a) provide information necessary for understanding the HIV/AIDS problem in the SADC region; (b) elucidate public policy and regulatory frameworks and their impact on community-based interventions; and (c) enable Kellogg Foundation to implement strategies and programs at a regional level.

Dr. Shisana is also the PI on South Africa's First Population-Based HIV/AIDS Behavioural Risks, Sero-Status, And Mass Media Impact Survey (2001-2002). This project was funded by the Nelson Mandela Foundation (NMF) administered through the Nelson Mandela Children's Fund (NMCF). The goal of this population-based research are to; a) identify prevalent risky behaviors that predispose South Africans to HIV infections; b) determine HIV prevalence in the population of South Africa using linked anonymous HIV saliva/blood test; c) link the behaviors with biological measures (without using names of people) to determine the association between the two; d) model the prevalence data and forecast probable infection levels for the next 10 years; e) identify the social, economic, political, structural and cultural contexts within which behavior occurs; f) identify obstacles to behavior change and determine if current mass media educational efforts take these factors into account; g) determine the extent to which current prevention, education and awareness programs and campaigns reach all sectors of the South African society, including the most vulnerable sectors of the population;and h) determine whether media messages are being understood and accepted, and by whom. The Nelson Mandela Children's Fund earlier requested the HSRC to assess the impact of current HIV/AIDS education and awareness programs designed to slow down the epidemic, including infection rates, stigma, and care and support for affected individuals and families. A Consortium developed to implement this project is lead by HSRC and include the Medical Research Council, Centre for AIDS Development, Research and Evaluation (CADRE), Family Health International (FHI), and Reproductive Health Research Unit (RPRU) of the University of the Witwatersrand. The HSRC is responsible for ensuring that the report is prepared and funding accounted for to the NMCF. The study began in September 2001 and will end in September 2002. Dr. Shisana is the Principal Investigator of the SAHARA project with Headquarters in Cape Town, South Africa. There are four regional offices of SAHARA including the West African Region in Dakar, The east African Region in Nairobi, the Central African region in Widhoek and the Southern African region as well as the headquarters in Cape Town, South Africa.