NeuroAIDS in Cameroon: Molecular determinants

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DESCRIPTION (provided by applicant): HIV-related neurocognitive disorders (HNCD) are common in infected patients, ranging from neurocognitive deficits to dementia. These complications have been well documented, both in the pre- and post-antiretroviral therapy (ART) periods. However, the vast majority of these studies were done in developed countries and involved patients infected with the predominant B subtype of HIV-1. Twenty six of the 40.3 million people currently living with HIV/AIDS are in sub-Saharan Africa and 83% of AIDS patients from this region do not have access to ART. Current published studies on neuroAIDS in Africa are mostly case reports and there is a need for structured, well-controlled studies that assess the incidence and prevalence of HNCD among infected people in Africa. A recent study in Uganda suggests that infection with HIV-1 subtype D compared to other clades increases the likelihood of rapid death from AIDS. The HIV epidemic in Cameroon is unique and is characterized by a very broad genetic diversity; infection with multiple HIV strains has been documented in Cameroon. The effect of this genetic diversity on the susceptibility and development of neuroAIDS is not known. Furthermore, whether other HIV genotypes differ in incidence, prevalence, or rate of progression of neuroAIDS or in systemic HIV manifestations is unclear. We hypothesize that HIV genotype can influence the patient's susceptibility to neuroAIDS and disease progression. The principal investigator has initiated a collaboration with the University of Yaound¿ to characterize the epidemiology of neuroAIDS in Cameroon and its molecular determinants The objective of this pilot study is to adapt, normalize and implement in Cameroon neuromedical and neurobehavioral test procedures, demonstrate the feasibility of collecting and transferring samples to UNMC for molecular testing: Aim 1: Train Cameroon investigators in neuromedical and neurobehavioral testing, Aim 2: Pilot test in Cameroon of a subset of a National Institute of Mental Health AIDS workgroup-recommended neuropsychological test battery; and neuromedical evaluation of HIV+ patients; Aim 3: Establish the feasibility of transferring samples from Cameroon to the University of Nebraska Medical Center and set up molecular studies by sequencing the HIV envelope in a small group of samples from HIV+ patients with and without HNCD. This phase of the study will determine the feasibility of identifying and recruiting participants, implementing NP test instruments in Cameroon and getting samples. It will provide normative data for neurocognitive testing among Cameroon population and lay the ground work for our future R01 which objective will be to perform a more definitive study of the epidemiology and molecular determinants of neuroAIDS in Cameroon. PROJECT RELEVANCE Neurological complications are common among HIV-infected individuals and there is a need to study theses complications in sub-Saharan Africa, the region worst affected by the HIV/AIDS pandemic. This proposal investigates whether infections with HIV isolates that have a particular genetic characteristic makes patients more susceptible to neurocognitive disorders. It will provide knowledge on the epidemiology of neuroAIDS in Cameroon and build the capacity for future neuroAIDS research and therapeutic testing in Cameroon.