Overlapping geographic distributions have brought malaria and HIV together in many regions of the world. When the two infections occur in the same individual, their interactions adversely affect the outcomes of both diseases. Malarial episodes, for instance, hasten HIV disease progression and HIV+ patients are more likely to contract malaria. This knowledge regarding malaria and HIV co-infection comes from microscopy-based studies conducted in sub-Saharan Africa where Plasmodium falciparum is endemic. We cannot extrapolate these findings directly to our study population in southern India. In our proposed cohort, there is predominantly unstable malaria transmission with P. vivax. Recent preliminary studies from India have demonstrated a prevalence of neuropsychological impairment (NPI) in HIV+ individuals and other studies have shown NPI in individuals with malaria in the absence of the severe clinical syndrome of "cerebral malaria". Even though these dangerous pathogens can infect the same host, their combined effects on the brain are virtually uninvestigated. The overall goals of this project will be:
- To identify malaria co-infection and confirm treatment success using a highly sensitive assay, and
- To demonstrate the effects of previously undetected malaria on HIV disease progression and neuropsychological (NP) performance in HIV+ individuals in southern India.
The findings of this study will:
- lead to improvement in HIV/AIDS care of our study population through screening and treatment of asymptomatic malaria,
- make it possible to apply for NIH and other funding to expand the program, and
- stimulate research to determine the mechanism behind NPI in co-infected people.
UCSD has a long partnership with YRG CARE in Chennai, India. This includes a long partnership in the AIDS Clinical Trials Group where HIV clinical trials are conducted for new antiretrovirals and new uses for these medications. These studies are led by Drs. Constance Benson
and Robert Schooley
at UCSD and Dr. Monika Kumaraswamy at YRG CARE. There are also studies in developing and validating diagnostic and treatment monitoring platforms at YRG CARE, including T cell and viral load assays. These studies are led by Drs. Benson, Bharti, Schooley and Smith at UCSD and Dr. Kumaraswamy and Dr. Saravanan at YRG CARE. Many of these technology based studies are in collaboration with the San Diego Center for AIDS Research (SD CFAR).
NeuroAIDS in India
Viral and host factors, as well as comorbidities, play key roles in determining susceptibility to the neurologic
complications associated with HIV infection. Most studies of HIV-related neurocognitive impairment have been conducted in Western countries, where HIV clade B predominates. Worldwide, however, clade C is much more common and recent virologic studies suggest that its neurovirulence may differ from clade B. Approximately 5 million individuals are infected with HIV in India, the vast majority with clade C virus. In the present study we will address the following aims within an Indian cohort:
- To determine the prevalence and nature of HIV-associated neurocognitive impairment (HNCI) in HIV-infected individuals who are not on antiretroviral (ARV) therapy,
- To determine the impact of newly-initiated ARV treatment on cognitive functioning,
- To assess the viral (env, tat) genetics associated with HNCI, and
- To determine the relationship between HNCI and host immunogenetic factors (i.e., genotype MCP-1, CCL3L1 copy number, RANTES and polymorphisms in CCR5/CCR2 to define CCR5 haplotypes).
Building upon collaboration between the HIV Neurobehavioral Research Center (HNRC) in the U.S. and the National AIDS Research Institute (NARI) in Pune, India, we propose to examine 300 HIV+ individuals prior to initiation of ARVs in linked studies (HPTN 052, India National AIDS Control Organization program) and follow them annually thereafter. We will also enroll an HIV seronegative comparison group in order to establish neuropsychological norms for determining impairment in individual HIV+ persons. The feasibility of this study has been demonstrated by a pilot study in which we created Marathi-translated instruments, trained India personnel, and examined 60 participants using methods originally developed at the HNRC but adapted to India. This project will potentially a) lead to improved understanding of the characteristics and correlates of neurologic complications of clade C HIV infection in India and b) enhance existing clinical and scientific expertise in India via technology transfer in the areas of cognitive assessments, genomics, and biomarker assays.
Members of the Human Neurobehavioral Research Center (HNRC) are collaborating with hospitals in Pune and Chennai, India and have established a cohorts of individuals with HIV that are enrolled in several studies looking at the effects of HIV on the central nervous system. This study aims to determine neurobehavioral effects of HIV and co-infections that influence neurobehavioral outcomes. These investigations include Drs. Ajay Bharti
, Scott Letendre
, and Davey Smith
University of California, San Diego
HIV Neurobehavioral Research Center
Antiviral Research Center
150 West Washington Street
San Diego, California 92103
Telephone: (619) 543-8080
HIV Neurobehavioral Research Center
HNRC International Core