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COMPLETED PROJECT
Screening for peripheral neuropathy and dementia requires simple clinical evaluation that should be done quickly for assessing the condition. We did a pilot study by simple peripheral neuropathy screening examination in our clinic in 48 HIV infected and 48 uninfected individuals.
Symptoms suggestive of peripheral neuropathy were more and vibration extinction time was significantly less (p < 0.05) in HIV infected individuals than controls. Nearly 17 of 48 HIV (+) subjects had low scores on the IHDS screen (i.e., < 10) and 7 of 48 HIV (-) subjects had an IHDS scores of < 10. On analysis of the components of the IHDS, it was found that the differences between the HIV (+) and HIV (-) subjects were significant for both the memory recall and the psychomotor speed portions of the exam with psychomotor speed being the most distinguishing test. These portions of the IHDS were the most sensitive for picking up the early changes associated with HIV dementia, similar to that found in the previous study. As peripheral neuropathy could occur in symptomatic as well as asymptomatic HIV infections, physicians could look for this carefully, confirm the diagnosis by further neurological and laboratory evaluations, identify the cause and treat the patient to improve his/ her quality of life.
Publication:
D. Riedel, M. Ghate, M. Nene, S. Mehendale, R. Bollinger, N. Sacktor, J. McArthur, A. Nath Screening for HIV dementia in an HIV -infected population in India. J Neurovirol 2006 Feb; 12(1);34-8
2. Study on neuro-cognitive aspect in HIV infected individuals
To standardize neurocognitive and neurological assessment methods developed at the University of California, San Diego (UCSD). The instruments include standardized neuropsychological (NP) tests and self-report questionnaires. Neurological assessment includes a general neurological history, examination and assessment of neuropathy. Psychiatric assessment is done to assess depression, and use frequency and quantity of assessment of substance use.
The mean raw NP test scores for the HIV+ group were worse than those for the HIV- group on all measures, with medium effect sizes found on tests within most domains. With respect to overall functioning, the HIV+ group had lower mean T scores compared to the HIV- group. In addition, they had a higher score (worse performance) on the Global Deficit Score (GDS), a summary score that reflects the level of impairment across the entire battery. The NP test battery consisted of 15 individual test measures, each assigned to 7 ability areas (fluency, speed processing, attention, executive functioning, memory recall, motor and learning) thought to be especially vulnerable to effects of HIV on the brain. Results indicate that the NP battery chosen for this study was understood and accepted by both the HIV+ and HIV- Indian participants, and appeared to be sensitive to the neurobehavioral effects of HIV and thus will be appropriate for bigger studies in future.
Objective:
To evaluate the efficacy and safety of RNTCP (intermittent short course) regimens in patients with HIV/TB and to study the relapse rates.
Study Design: For the study, 283 pulmonary TB patients untreated for TB in the past were enrolled. Of these, 163 were HIV seronegative and 120 were HIV seropositive. Of the HIV seronegative tuberculosis patients enrolled, 77.9% were male, while among the HIV seropositive tuberculosis patients, 82.5% were male.
Progress made so far: This study was carried out in collaboration with the Talera Hospital located in the Pimpri-Chinchwad Municipal area near NARI. The regimens used for TB were the same as that used by the Revised National TB Control Programme (RNTCP) and the treatment was given by Directly Observed Treatment (DOTS).
Future steps and targets to be achieved: The enrolments and the follow ups in the study have been completed but the second draft f the manuscript is in the process of being completed.
Objectives:
- To generate HIV-1subtype C env, gag and codon optimized env expressing recombinant plasmids.
- To study the immune responses to various recombinant plasmids and their combinations in mouse model (with or without coadministration of IL-12 and GM-CSF expressing plasmids)
- To study the effects of DNA prime protein boost strategy on mouse immune responses.
Study Design: The project addresses the issue as to whether HIV-1 subtype C based recombinant DNA constructs would serve as probable vaccine candidate. It was proposed to generate gp150 and gag DNA clones from the PBMCs obtained from HIV-1 preseroconverters.
The rationale for selecting specimens from seroconverter is that the invading HIV-1 strain could not have undergone mutations under the host immune pressure and it is assumed that such viruses could be antigenically very similar to the transmissible viruses.
The rationale for selecting specimens from seroconverter is that the invading HIV-1 strain could not have undergone mutations under the host immune pressure and it is assumed that such viruses could be antigenically very similar to the transmissible viruses.
Based on the available sequences of env gene from Indian isolates consensus sequence for gp150 was derived. The synthetic gp 150 construct was to be commercially obtained.
Humoral and cell mediated immune responses induced by codon optimized gp150 gene would be compared with that induced by the corresponding gene obtained from the patients specimen in a mouse model. It is known that interleukin genes or GM-CSF and other immunomodulating genes if co-administered enhance immune responses. It was proposed to test the effects of IL-12 and GM-CSF expressing genes from the humoral and cell mediated immune responses induced by HIV-1 env/gag DNA constructs.
The above mentioned DNA constructs would be tested in different combinations for immune responses. The best combination of env and gag with or without IL-12 and GM-CSF would be used to prime the immune responses and the same mice would then be boosted with recombinant vaccinia/killed HIV virions to check the booster effect.