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International Health

South Africa
HIV/AIDS & TB Research
Impacting Local and Global Health Care

Impacting Local and Global Health CareSince 2000, Dr. Jean Nachega, associate scientist in International Health and Epidemiology, as well as professor of Medicine and Director of the Center for Infectious Diseases at Stellenbosch University, Cape Town, South Africa, has been working on methods to improve prevention, diagnosis, and treatment of HIV/AIDS and tuberculosis in South Africa. His early work there under Dr. Richard Chaisson, professor in Epidemiology and International Health, and director of the Johns Hopkins Center for Tuberculosis Research, has led to an expanded HIV & TB research presence for the Department in the country, culminating most recently with a 5-year, $10 million training grant from the President’s Emergency Fund for AIDS Relief (PEPFAR) that will open up opportunities for Hopkins faculty, fellows, residents, and students to teach and conduct research in the country.

Dr. NachegaPreventing the Spread of TB through Active Case Finding
Dr. Nachega was born in Zaire, now the Democratic Republic of Congo (DRC), and as an adolescent left as a refugee due to civil unrest. He settled in Belgium and later the United States. However, his dream was always that one day he would return to Africa and play a role in improving the well-being of African people.

In 2003, Nachega’s dream of returning to Africa came true when he was assigned to lead HIV and TB projects in South Africa. There, Dr. Nachega and colleagues conducted a study to assess the effectiveness of screening all HIV-positive mothers for TB. Preventing the spread of TB can prove difficult because, among many other factors, infected individuals often don’t go to the doctor until their symptoms are well advanced. Detecting TB among HIV-positive mothers and their children is especially important, given the vulnerabilities of both these groups.

The study, conducted at a clinic for expectant and new HIV-positive mothers in Soweto, South Africa, found that over 10 percent of patients had active TB. Without testing, many of these women would have continued exposing their newborns to TB before seeking medical attention.

This study along with others has provided support for using active case finding to better prevent the spread of TB. As opposed to treating TB when patients seek care because symptoms are so severe, active case finding can be especially useful in areas that have both a high-prevalence of TB and HIV. The World Health Organization, for instance, with evidence such as this from South Africa, has begun recommending active case finding whenever economically feasible. 

DOT-HAART TeamRolling out HAART in Developing Countries
Early last decade, donors and health professionals worldwide began debating the feasibility of rolling out HIV treatments in developing countries. Costs for Highly Active Antiretroviral Therapy (HAART) began to decrease. However, there was much debate over the ability of patients in lower resource areas to adhere to complicated drug therapies. In addition to the many side effects, lack of reliable electricity and clean water, for instance, were thought to pose insurmountable barriers to proper adherence. Donors were worried that their investments might not lead to lower viral loads and decreased mortality rates. 

In 1997, as part of a post-doctorate fellowship in Brussels, Belgium, Dr. Nachega had the opportunity to go back to his home country DRC for a clinical rotation at Mama Yemo Hospital in Kinshasa. His experience there committed him to fighting the HIV/AIDS epidemic in Africa:

I witnessed first-hand the state of the HIV epidemic in Africa and its devastating effects on all aspects of human life. By 1996, the introduction of HAART in developed countries provided hope for those with HIV who could afford therapy, but for most in Africa, this hope was completely beyond reach. I became completely committed to changing this.

Through a pilot grant from the JHU Center for AIDS Research (CFAR), Dr Nachega, with other IH faculty and South African colleagues, led a study in Soweto to monitor adherence levels. His study showed patients were able to follow complicated drug regimens at overall levels as high as or higher than in developed countries. His 2004 publication in the journal AIDS presenting these data caught the attention of Canadian researcher Edward Mills from McMaster University. 

Mills asked Nachega to join him in a meta-analysis of global HAART adherence levels. Their collaboration with others from around the world led to their ground-breaking 2006 article published in JAMA. It showed that despite economic stresses, lack of amenities, and unemployment, adherence levels were better in sub-Saharan Africa than in North America. The evidence from this analysis allayed donors’ fears of wasted investments and possible drug resistance. Former President Bill Clinton even cited the meta-analysis paper in his address to the Toronto AIDS conference (October 2, 2006, Canada Newswire).

Addressing Adherence Problems
While adherence levels in South Africa remain high, some groups such as youth and IDUs have not fared as well. Moreover, evidence has shown that adherence levels in North America began to drop several years after the first introduction of HAART. Therefore, researchers are now pursuing methods for maintaining Africa’s high adherence levels while also addressing problems among certain populations. 

In 2008 with major funding from the National Institute of Allergy and Infectious Diseases, Dr. Nachega led an intervention to assess the effect of a TB protocol—Directly Observed Therapy, Short-course (DOTS)—on HAART adherence levels. Because HIV therapy lasts a lifetime—not 6 months as with DOTS to treat TB—intervention patients were asked to choose a support person from their family or neighborhood who could commit to helping them stick to their regimen for 1 year.

Stellenbosch UniversityAt a clinic in Cape Town, clients were randomly divided into two groups: (1) the intervention clients who chose a support person to help monitor their daily medicine dosing; (2) and the control clients who self-monitored. While the study found that mortality levels were lower among the intervention group, viral loads and adherence levels were no different. Dr. Nachega speculates on why this might be the case:

The ‘social capital’ provided by a trusted patient-nominated treatment supporter, such as emotional support or encouragement to seek care, may have contributed to saving lives, regardless of the observational component of the intervention. But more research into exact causes needs to be pursued.

Cost Savings through High Adherence Levels
In 2010, Dr Nachega in collaboration with Dr. David Bishai, professor in Population, Family and Reproductive Health and International Health and South African colleagues, performed the first analysis to quantify the dollar amount HAART adherence costs health insurance organizations. Using data from a private health insurance system in South Africa, they found that any increase in cost due to high levels of adherence was more than offset by reduced hospitalizations. Patients who had very high levels of adherence also had the lowest hospitalization rates. The study was published in the prestigious Annals of Internal Medicine, and results have already led to increased interest from insurers, hospitals and governments in developing interventions to promote and maintain adherence levels.

Medical Education Partnership
Initiative (MEPI) in South Africa

The MEPI is a 5-year, $10 million project to improve capacity in sub-Saharan Africa which is funded by PEPFAR and the NIH. Its goal is to increase the number of new health care workers and strengthen local medical education systems and to build clinical and research capacity. 

Associate Scientist Jean Nachega is the principal investigator of the grant based at Stellenbosch University where he holds a faculty appointment and is director of the Center for Infectious Diseases. In addition to Johns Hopkins and Stellenbosch Universities, partners include Makarere University in Uganda; the University of Cape Town’s Lung Institute’s Knowledge Translation Unit; and the Karolinska Institute in Sweden.

The main training and research site of the project will be located in a rural community 100km outside of Cape Town called Worcester. For over 5 years, Stellenbosch has been investing in that community’s capacity to provide quality health care and HIV services. The initiative will help build on this investment and includes the following focus areas:
• Capacity-building of health care professionals to treat HIV
• Health systems research and operational research
• Pharmacology
• Public health training in biostatistics and epidemiology
• Infectious disease clinical training

The grant will also open up specific opportunities for Johns Hopkins faculty and students:
• Faculty support to teach short courses in South Africa
• Resources and infrastructure for students and faculty to teach, do rotations, and conduct research in country  

For more information see Stellenbosch University’s Center for Infectious Diseases

Selected Ongoing TB and HIV Research
With support from the European Developing Countries Clinical Trial Partnership (EDCTP), Dr. Nachega is implementing a randomized clinical trial evaluating the efficacy of non-steroid anti-inflammatory drugs to prevent tuberculosis associated immune reconstitution syndrome, a common complication which can occur  within a few weeks of initiation of HAART in patients with very weak immune systems. Also, a team of JHU-Stellenbosch researchers is investigating whether gene polymorphism on  chromosome 22 is a risk factor  for HIV-associated kidney disease in South African adults.

The Medical Education Partnership Initiative at Stellenbosch University
For over 10 years, Dr. Nachega has been tirelessly looking for new and improved ways to avert deaths among the HIV-infected. His latest project is leading a 5-year, $10 million training grant to increase local HIV-related medical capacity in rural South Africa. While full-time faculty at Hopkins, Nachega also has an appointment at Stellenbosch University in South Africa and is the first director of that university’s Center for Infectious Diseases. The Center’s 2010 Medical Education Partnership Initiative grant from PEPFAR will open up more opportunities for Hopkins faculty and students—as well as from other research centers and medical institutions around the world—to improve the capacity of health professionals and communities to care for and treat those affected by HIV and tuberculosis.

Dr. Nachega’s work demonstrates his continued commitment to improving the well-being of those suffering from the HIV/AIDS epidemic in Africa. While many obstacles remain, he is optimistic:

I believe we will observe a dramatic improvement in the health of African nations and that the treatment and prevention of HIV/AIDS will be the largest single public health effort to attain a greater state of health in Africa.

Select AIDS and TB articles by IH faculty working in South Africa
Tuberculosis active case-finding in a mother-to-child HIV transmission prevention programme in Soweto, South Africa. Nachega J, Coetzee J, Adendorff T, Msandiwa R, Gray GE, McIntyre JA, Chaisson RE. AIDS. 2003 Jun 13;17(9):1398-400. 

Active case finding of tuberculosis: historical perspective and future prospects. Golub JE, Mohan CI, Comstock GW, Chaisson RE. Int J Tuberc Lung Dis. 2005 Nov;9(11):1183-203.

Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa. Nachega JB, Stein DM, Lehman DA, Hlatshwayo D, Mothopeng R, Chaisson RE, Karstaedt AS. AIDS Res Hum Retroviruses. 2004 Oct;20(10):1053-6.

Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. Mills EJ, Nachega JB, Buchan I, Orbinski J, Attaran A, Singh S, Rachlis B, Wu P, Cooper C, Thabane L, Wilson K, Guyatt GH, Bangsberg DR. JAMA. 2006 Aug 9;296(6):679-90. 

   Randomized controlled trial of trained patient-nominated treatment supporters providing partial directly observed antiretroviral therapy. Nachega JB, Chaisson RE, Goliath R, Efron A, Chaudhary MA, Ram M, Morroni C, Schoeman H, Knowlton AR, Maartens G. AIDS. 2010 Jun 1;24(9):1273-80.

Association of antiretroviral therapy adherence and health care costs. Ann Intern Med. 2010 Jan 5;152(1):18-25. Nachega JB, Leisegang R, Bishai D, Nguyen H, Hislop M, Cleary S, Regensberg L, Maartens G.

Evaluation of paradoxical TB-associated IRIS with the use of standardized case definitions for resource-limited settings.  Eshun-Wilson I, Havers F, Nachega JB, Prozesky HW, Taljaard JJ, Zeier MD, Cotton M, Simon G, Soentjens P. J Int Assoc Physicians AIDS Care (Chic). 2010 Mar-Apr;9(2):104-8.

--Brandon Howard, February 2011