K-RITH

The HIV epidemic continues to expand at an alarming rate, particularly in those regions of the world least able to cope financially and medically.

At the epicenter of the HIV epidemic is KwaZulu Natal Province, South Africa, where recent seroprevalence studies in a large township revealed that 66% of 23 year old women attending an antenatal clinic were HIV infected. This province is also at the epicenter of the expanding TB epidemic that is being fueled by HIV. In recent studies performed by Dr. Willem Sturm, fully 90% of persons with TB in KZN province are coinfected with HIV, and approximately 30% of those with HIV are TB-coinfected.

Despite the intersection of these two epidemics, research efforts in TB and HIV remain largely isolated from one another, and currently there are no integrated TB-HIV research efforts anywhere in the world. Advances in dealing with these co-epidemics is highly dependent on the availability of samples from infected persons, and since rapid translation of research advances to the bedside will require an infrastructure in a highly endemic area, therefore the Howard Hughes Medical Institute (HHMI) along with The University of KwaZulu Natal (UKZN) created the KwaZulu Natal Research Institute for TB and HIV (K-RITH) following the model of the success of the Doris Duke Medical Research Institute (DDMRI).

The K-RITH scientific plan consists of 4 highly coordinated lead programs, each containing a primary project as well as subprojects embedded in these that will be conducted by collaborating investigators funded through HHMI grants. Each of these programs has clearly defined local leadership and strong international collaborations:

• Diagnostics: Rapid diagnostics geared toward solving the clinical challenges in the field form a major investigative platform, and will create a center for the rapid evaluation of other diagnostic tests as they become available.
• Therapeutics: The K-RITH therapeutics program is largely focused on TB therapy and TB drug resistance. Through the use of the patient cohort that represents ground zero in the TB epidemic, we aim to provide answers to the question of what determines the fate of a patient. Sequencing of the strains to be collected will also lay the groundwork for rapid molecular based genetic testing for drug resistance.
• Immunology and Vaccine: Understanding the immune response to TB, particularly in the setting of co-infection with HIV, is key to the design and testing of vaccines for both infections.

TB /HIV pathogenesis/reactivation: Recurrent TB accounts for the majority of TB cases in countries like South Africa where TB incidence is high. Knowledge of whether TB recurrence is predominantly due to re-infection or reactivation has important implications for TB control as re-infection requires a substantially different set of public health and infection control interventions compared to reactivation.

The ultimate goal of K-RITH is to establish a center of scientific research excellence in the center of the worst convergence of the TB and HIV epidemics, and through this to focus research efforts toward rapid translation for the betterment of human health. Already this major investment has drawn in other African institutions to partake of the training opportunities being offered, and these linkages and the expertise created provide an ideal platform for expansion of this model to other sites.