Wednesday, February 5, 2025
2/5/2025
DESCRIPTION (provided by applicant): HIV/AIDS is fast becoming a major threat in the Indian sub-continent with a steep increase in the number of AIDS cases. South India is one of the regions hardest hit by HIV/AIDS. The increasing number of AIDS cases has a direct impact on the already overburdened public health care system and warrants optimal management of AIDS cases with a special focus on antiretroviral therapy. The recent Government of India antiretroviral therapy (ART) roll-out program under the 3 million by 5 global initiative, has made it possible for many to have access to first line NNRTI based ART. As second line therapy is not available in India due to cost, the need for the initial regimen to be durable is critical. HAART regimens may fail because of insufficient adherence, viral resistance or because intestinal dysfunction leading to poor absorption of antiretroviral agents. The central hypothesis of this proposal is that more than 50% of those who become eligible for HAART in India will have marked intestinal dysfunction in terms of absorption capacity that will potentially lead to sub-therapeutic levels of antiretrovirals in plasma, failure of therapy and emergence of viral resistance. A longitudinal cohort study to test this hypothesis is proposed which will measure adherence, intestinal function and development of resistance. Specific aim 1 will determine the prevalence of intestinal dysfunction in a cohort of HIV infected individuals in India, at the time of initiation of HAART using the tests d-xylose and mannitol:lactulose excretion in the urine following oral administration of these sugars. Specific Aim 2 will determine the association between intestinal dysfunction and response to HAART as measured by CD4 cell count and BMI at baseline, 6 and 12 months and viral load and viral resistance mutation at baseline and 12 months in a cohort of HIV seropositive individuals initiated on nevirapine based HAART. Specific Aim 3 will document change in intestinal function at 6 and 12 months in response to the initiation of nevirapine based HAART, and specific aim 4 will determine the association between intestinal dysfunction and levels of nevirapine administered in the fixed dose combination preparations provided through the Government of India roll out ART program in India. Nevirapine levels will be measured 2 weeks after the initiation of the treatment, at 2hrs after morning dose and again at 6 and 12 months. This proposed study offers an opportunity to objectively measure the magnitude of the intestinal dysfunction at the time of start of HAART in India, and its impact on failure of therapy and emergence of viral resistance mutations. The data from this proposed study will inform future directions in the management of HIV/AIDS in India. PUBLIC HEALTH RELEVANCE: About 80% of the People Living with HIV/AIDS in India can have access to antiretroviral therapy (ART) only through the public funded ART roll-out program. The current policy in India is to start NNRTI based HAART when the CD4 cell count drops to d200 cell/mm3. As second line therapy is not available in India through the public funded ART program due to cost, the need for the initial regimen to be durable is critical. This proposed longitudinal study has policy implications at the national program level, if a significant proportion of patients found to have intestinal dysfunction at a CD4 cell count of d200 cell/mm3, and it is associated with sub-therapeutic levels of nevirapine and failure to therapy.
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