India: Chennai

YR Gaitonde Center for AIDS Research and Education
(YRG CARE), Chennai, India

HISTORY OF COLLABORATION WITH YRG CARE

In 1996, a Miriam Hospital house officer, Dr. Geetha Gopalakrishnan, brought to the attention of several of the Brown faculty the fact that there was a dynamic non-governmental organization in southern India called YR Gaitonde Center for AIDS Research and Education (YRG CARE) that was increasingly becoming a leader in community-based care and research for people living with HIV in southern India. Geetha wanted to spend an elective at YRG CARE. Dr. Flanigan, and Dr. Mayer, the Director of the Brown-Tufts Fogarty AIDS International Research and Training Program, discussed the organization with colleagues at Johns Hopkins who had been working extensively in India and they felt that this organization could provide an excellent training experience. Based on Geetha’s initial experience, a multi-lateral collaboration has developed that has resulted in frequent exchanges of faculty, collaborations, leading to several important collaborative projects and NIH grants, including YRG CARE’s involvement in the HIV Prevention Trials Network (HPTN) and AIDS Clinical Trials Group (ACTG), as well as more than 30 collaborative publications.

YRG CARE was founded by Dr. Suniti Solomon, an Infectious Disease physician, who had been one of the first clinical researchers to describe the HIV epidemic in India in the mid-1980's. She felt that she could do more innovative work at an independent agency and left government and academic service and created YRG CARE, a trust named after her father, Mr. Y. R. Gaitonde. YRG CARE currently cares for more than 5,500 people living with AIDS/HIV and is the largest prescriber of antiretrovirals in southern India. She has attracted an extremely talented staff, including Dr. N. Kumarasamy, Dr. T. Yeptoni, Mr. A. K. Ganesh, and Mr. A. K. Krishnan. This leadership team is now managing a staff of more than 100 individuals and has conducted important research that has defined the natural history of HIV in southern India, the spectrum of opportunistic infections that people with HIV sustain, and has delineated the culturally-appropriate ways to prevent HIV transmission. YRG CARE has been an important teaching center for Brown University students, and over each of the past seven years, at least one Brown student has spent an extended period of time at YRG CARE working on research projects. Brown students helped collaborate on an important manuscript that delineated the fact that monogamy was a major risk factor for HIV transmission in India because of the reticence of husbands to use appropriate prevention methodologies even after they had contact with sex workers.

The laboratory at YRG CARE created with the support of the NIAID and NIMH grants, is now more than 2,500 square feet and is able to perform the latest diagnostic technologies, including HIV, gonorrhea, and chlamydia PCR. The lab also performs CD4 lymphocyte counts on site, and has its own autoanalyzer.

Dr. Ken Mayer at the dedication of the new floor of YRG Care, Chennai

Brown University faculty that have developed collaborative projects in India include: Dr. Susan Cu-Uvin, who is studying mother-to-child transmission as well as the seroprevalence of HIV in antenatal cohorts in Chennai (Madras), where YRG is located; Dr. Geetha Gopalakrishnan, who is studying women's reproductive health attitudes and endocrine and metabolic issues in HIV-infected individuals before and after antiretroviral therapy; and Dr. Mark Lurie, who is developing collaborations to study truckers and other migratory workers who may acquire and transmit HIV throughout southern India. Dr. Kenneth Mayer, the PI of the Brown-Fenway HIV Prevention Trials Unit (HPTU) has developed a collaboration with Drs. Solomon and Kumarasamy and staff to conduct HIV Prevention Trials in Chennai. Dr. Timothy Flanigan, the principal investigator of the Brown NIH AIDS Clinical Trials Unit has developed a collaboration with Dr. Kumarasamy and Dr. Solomon to set up an international NIH clinical trial unit at YRG CARE. Drs. Flanigan and Mayer have collaborated with colleagues at YRG CARE to develop cost-effective mechanisms to evaluate the natural history and effect of antiretroviral therapy on infected individuals. Because the cost of antiretrovirals has decreased considerably over the past few years because of the large number of generic drug manufacturers in India, some of the more expensive issues that people with HIV have to confront are the costs of diagnostic monitoring. Thus, Drs. Flanigan, Mayer and YRG CARE colleagues have attempted to develop strategies that can develop new and cheaper technologies and to use previous standardized tests, such as the total lymphocyte count, to add an increased saving while at the same time helping to predict the clinical course of individuals with HIV infection. Brown University faculty have participated in several local, regional, and national trainings facilitated by YRG CARE to spread knowledge of best practices for HIV care in southern India. This past March, Drs. Flanigan, Mayer and Carpenter traveled to Chennai and collaborated with colleagues from Johns Hopkins University in a five-day training program to help develop clinical investigators who would be participating in international therapeutic and prevention research projects. Dr. Mayer and A.K. Ganesh have received funding from the World AIDS Foundation to train laboratories and healthcare providers to improve the quality of HIV diagnostic services in Southern India. Several articles have been published in various journals such as The Lancet Infectious Diseases, Journal of AIDS, Clinical Infectious Diseases and the International Journal of STD & AIDS. Topics include Monitoring HIV Treatment in the Developing World, TLC as a Useful Tool for Opportunistic Infection Prophylaxis in India and Other Resource-constrained Countries, the Natural History of HIV Disease in Southern India, and Dried Blood Spots: a Valuable Tool for HIV Surveillance in Developing/tropical Countries.

Dr. Suniti Solomon, Founder and Director, YRG Care presenting at the Consensus Conference

HIV PREVENTION TRIALS NETWORK

The NIH HIV Prevention Trials Network (HPTN) is a multi-national network funded by the National Institutes of Allergies and Infectious Diseases and managed by Family Health International. Our CFAR’s HPTN collaboration began in 2000, including Fenway Community Health in Boston; Brown University, based at The Miriam Hospital; as well as YRG CARE in southern India. This clinical trials network is designed to be able to answer large public health questions about different prevention interventions, other than HIV vaccines. The first studies in Chennai in the HIV Prevention Trials Network have included an assessment of risk factors associated with HIV transmission in southern India, focusing on the recruitment and retention of men and women who attend sexually transmitted disease clinics, have multiple sexual partners, and are in HIV serodiscordant relations. A sub-study of this initial trial (HPTN 033) evaluated the prevalence of sexually transmitted infections in Chennai, and found that more than 30% of the men and women recruited in the study were infected with Herpes Simplex Type 2, the most common sexually transmitted infection locally. Among the women, almost 10% had trichomoniasis, and syphilis was almost equally prevalent.

Kate Morrow, Ph.D Dr. Solomon., Robbie Singal, A.K. Srikrishnan, and AK Ganesh

YRG CARE will be one of the seven international sites for the NIH HPTN's 052 study, which will be a randomized control trial to evaluate whether early institution of antiretroviral therapy will decrease HIV transmission in HIV discordant couples. Over the next year YRG CARE will be doing the preparatory work to develop this protocol, which will include standardizing their protocols for couples counseling, evaluating the willingness of participants to participate in a study of this type, working with their community advisory board and their institutional review board to ensure that the appropriate community input and ethical review are underway before undertaking this ambitious and complex protocol.

AIDS CLINICAL TRIALS NEWORK

YRG Care in Chennai, India is partners with The Miriam Hospital, Brown University AIDS Clinical Trials Unit to develop and undertake clinical trials to improve antiretroviral therapy in resource-limited settings. YRG Care has received a reward from the National Institutes of Health/National Institutes of Allergy and Infectious Diseases as an ICTU (International Collaborative Treatment Unit). The first trial as part of the ICTU’s ACTG will be ACTG-5175 which will compare different antiretroviral treatment analyses. Drs. Flanigan and Kumarasamy are two of the co-chairs of this protocol. This is one of twelve units funded through the AIDS Clinical Trials Group (ACTG) to develop multi-center trials, to examine improved therapies for HIV, opportunistic infections such as tuberculosis, cryptococcal meningitis, and chronic diarrhea, and decrease long term toxicities, and hopefully costs of antiretroviral therapy in resource limited-settings. The twelve ICTUs are located in different parts of Sub-Saharan Africa, the Caribbean, Latin America, and Asia. The longstanding collaboration between Brown University and YRG Care in Chennai led to the development of expertise related to antiretroviral therapy. An R21 funded by NIH/NIMH was recently awarded to Drs. Flanigan and Paul to investigate the neurocognitive consequences of HIV/AIDS in South India. Over a dozen trainees from YRG Care have received training through The Miriam Hospital Immunology Center and other resources at Brown Medical School. A pilot trial of antiretroviral therapy using structured treatment interruptions (STIs) is ongoing. The support from the CFAR has been critical as a core resource to train faculty from YRG Care and develop the expertise needed for them to successfully compete in this endeavor.

The other multi-national study which involves YRG CARE is funded by the National Institutes of Mental Health. In this study YRG CARE will be participating with sites in China, Russia, Peru, and Zimbabwe to train popular opinion leaders in the local community and see if the diffusion of knowledge and values from these popular opinion leaders will result in decreased HIV transmission in the larger community.