Abstract
Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV preven-tion, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 42-50. |
| Journal | African health sciences |
| Volume | 22 |
| Issue number | 2 Special issue |
| DOIs | |
| State | Published - 2022 |
Keywords
- Makerere
- Rakai Region
- Uganda
- high impact HIV research
ASJC Scopus subject areas
- General Medicine
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In: African health sciences, Vol. 22, No. 2 Special issue, 2022, p. 42-50.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Makerere’s contribution to the development of a high impact HIV research population-based cohort in the Rakai Region, Uganda
AU - Kankaka, Edward Nelson
AU - Nalugoda, Fred
AU - Serwadda, David
AU - Makumbi, Fredrick
AU - Wawer, Maria J.
AU - Gray, Ronald H.
AU - Quinn, Thomas C.
AU - Reynolds, Steven J.
AU - Nakigozi, Gertrude
AU - Lutalo, Tom
AU - Kigozi, Godfrey
AU - Sewankambo, Nelson K.
AU - Kagaayi, Joseph
N1 - Funding Information: to markedly suppress HIV viraemia was available to patients in the US and other high-income countries as of 1987 16,17. However, AZT and other drugs developed subsequently, did not become available in Uganda until 2002, and initially only at the Joint Clinical Research Center in Kampala (using generic AZT imported from India). The drug only became available in Rakai in 2004, once The President’s Emergency Plan for AIDS Relief (PEPFAR) began to provide HIV drugs to selected countries around the world. Notably, RHSP was extensively involved in the Drug Access Initiative to make HIV treatment available in sub-Saharan Africa. The work on viral load and heterosexual transmission of HIV-1 by stage of infection in the Rakai cohort (Figure 3)13–15, led to the concepts of ‘treatment as prevention’, ‘universal test and treat’, and ‘undetectable= untransmissible’ which were confirmed by trials such as HPTN 05218. These concepts are now standard practice, including routine viral load monitoring of patients initiated on treatment. The RHSP has also evaluated more affordable assays for viral load monitoring in resource-limited settings19. In 2004-2007, an NIH-funded clinical trial proved the effectiveness of Voluntary Medical Male Circumcision (VMMC)20,21 along with two other clinical trials in Kenya and South Africa22,23, which confirmed that the procedure was safe, acceptable and reduced the risk of male HIV acquisition by over 50%. VMMC also reduced the risk of male acquisition of other STIs24,25; including in HIV-positive men26. The WHO and the Joint United Nations Program on HIV/AIDS (UNAIDS) recommended VMMC for HIV prevention in countries with high HIV burdens and low male circumcision prevalence27. It is now an integral part of HIV programs in over 14 countries in sub-Saharan Africa. Since the Rakai cohort was also the only of the threerials to include female partners, it was also able to show that VMMC was highly acceptable to men and their partners28,29, and significantly reduced male transmission of multiple STIs to these partners30. Through the cohort, more attention was drawn to the need for enhanced treatment of pregnant women and prevention of mother to child transmission (PMTCT)7. Effective modalities of delivering antiretroviral therapy to pregnant mothers and their infants were suggested31 and the benefit of continued breast feeding of HIV-exposed babies was demonstrated32, as well as the potential for integration of contraception services in HIV care for the mothers33. The Rakai cohort has also provided a platform to evaluate the impact of HIV combination interventions, including VMMC and antiretroviral therapy. In 2017, the RHSP documented the first population-level impact of combination HIV prevention including a 42% reduction in HIV incidence within about 10 years34 in the general population and 48% decline (within 5 years) in hyper-endemic fishing communities35. The RHSP, based on cohort has conducted multiple implementation research studies to determine how to improve the availability and acceptance of combined HIV prevention36,37. Since 2016, RHSP has supported a comprehensive HIV service program (beyond VMMC and ART) across 12 districts of the Masaka region (including Rakai) with funding from PEPFAR through CDC-Uganda. The program includes prevention services such as Pre-and Post-Exposure prophylaxis (PrEP and PEP), DREAMS—an HIV prevention program among adolescent girls and young women, programs to reach key and priority populations with treatment, and program to mitigate effects of intimate partner violence and to protect children. An ongoing collaboration with the PANGEA-HIV consortium, funded by the Bill and Melinda Gates Foundation, which includes multiple southern and eastern Afri- can cohorts, is assembling the most comprehensive data and analyses on HIV phylogenetics on the continent. With the Rakai cohort as the largest biospecimen contributor, the study has shown that “hot spots” such as fishing communities do not spread HIV to the general populations and that “super spreaders” do not play a major role in transmission38. Recent epidemiologic and phylogenetic data from the Rakai cohort and other cohorts in sub-Saharan Africa show that in a generalized African epidemic “many infect few”. By 2022, nearly 600 publications have come from this cohort and have been cited more than 20,000 times. The cohort is expanding to follow-up Rakai cohort participants who migrate to major urban areas in Uganda (Kampala and Masaka) to determine how such migration affects access to and use of HIV prevention and treatment, and importantly, any changes in NCD status (e.g., hypertension, asthma, and related conditions). “We owe this small community of committed researchers a debt of gratitude for all the knowledge they have given us, from their post on the front lines of this terrible scourge. Paraphrasing Sir Winston Churchill, never was so much owed by so many to so few!” Roger I Glass, Director, Fogarty International Center39. Funding Information: Supported in part (SJR, TCQ) by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The authors also appreciate the support from the Office of Cyberinfrastructure and Computational Biology (OCICB) at the NIAID. Funding Information: The “Rakai Project” started in 1988 and was boosted by funding from the NIH in 1989 to study the dynamics of HIV spread and its impact. The project was later re-named the Rakai Health Sciences Program (RHSP) in 2004 and continues as such to the present day. The first Rakai cohort included 21 randomly selected community clusters of about 30 households each along main roads, secondary roads and rural areas of Rakai (current day Rakai, Kyotera, and Lyantonde districts); and a total of around 1292 individuals who responded to interviews and provided blood samples. “There were no telephones or banks in Rakai. Money would be carried in sacks and quickly loaded into the land rover behind the bank building in Kampala to avoid curious eyes. In Rakai, we would spend the night at the Milano South View Inn in Kyotera Town, a very interesting place, and would spin blood samples with a hand-centrifuge under a single 40-watt light bulb dangling from the ceiling,” recalls Nelson. This work resulted in the first quantification of an HIV prevalence of up to 52.8% in some communities, as well as descriptions of the pattern of community spread - from main road trading centers, through intermediate trading villages, to rural agricultural villages (Figure 1)5. These data indicated that there was a public health emergency in the region. In the following years, additional funding from multiple funding agencies and foundations, including NIH, CDC, the World Bank, the Ugandan Ministry of Health, the Rockefeller Foundation, the Gates Foundation, the Walter Reed Army Institute of Research/Henry Jackson Foundation, and the Doris Duke Charitable Foundation enabled expansion of the Rakai project with establishment of a lab, inclusion of new communit clusters, provision of counseling services, and new HIV/STD stud- Funding Information: Nelson and David wrote proposals to several funding agencies including the WHO and the US Centers for Disease Control (CDC) and received encouragement but no funding. Eventually after two years, Columbia University learnt of the Rakai reports and of the frantic search for funding, and asked Maria J. Wawer, a physician/ epidemiologist to travel to Uganda to check out the potential for a small HIV/AIDS project, using a modest USAID grant left unexpended from a reproductive health project. Initially skeptical regarding research possibilities in Rakai, Maria was eventually convinced by the determination of David and Nelson, and a trip to Rakai. “So, we wrote a proposal for the use of the remaining USAID funds at Columbia University [$200,000 US dollars], got the go ahead, and the great adventure began,” says Maria. Publisher Copyright: © 2022 Kankaka EN et al.
PY - 2022
Y1 - 2022
N2 - Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV preven-tion, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.
AB - Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV preven-tion, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.
KW - Makerere
KW - Rakai Region
KW - Uganda
KW - high impact HIV research
UR - http://www.scopus.com/inward/record.url?scp=85136424109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85136424109&partnerID=8YFLogxK
U2 - 10.4314/ahs.v22i2.7S
DO - 10.4314/ahs.v22i2.7S
M3 - Article
C2 - 36321125
AN - SCOPUS:85136424109
SN - 1680-6905
VL - 22
SP - 42-50.
JO - African health sciences
JF - African health sciences
IS - 2 Special issue
ER -