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Comparison of Latent Activation Between Subtypes B and C of HIV

Award Number: F30AI195013
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/29/2026
PERIOD OF PERFORMANCE END DATE: 11/28/2027

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Comparison of Latent Activation Between Subtypes B and C of HIV - PROJECT SUMMARY Human Immunodeficiency Virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS) and is a key source of global morbidity and mortality. HIV subtype B (HIV-1B) is the most studied HIV subtype and is thought to be the most common in the western world despite only representing ~10% of global infection. Assumptions of parity between HIV-1B and other subtypes have often failed to incorporate known differences in pathogenesis, antiretroviral therapy efficacy, and cell tropisms of non-B subtypes, widening disparities in the study of non-B HIV infection. Domestically, intravenous drug use-associated HIV transmission is a key driver of new infections and is highly associated with viral recombination. Recent data documented a surge of non-B HIV in Kentucky and Ohio – a potentially fatal, unaccounted-for threat to the Department of Health and Human Services “End the HIV Epidemic” 2030 agenda. In all subtypes, current treatments slow progression but do not cure the infection because of the persistence of a latent viral “reservoir” (LVR) that re-seeds infection upon therapy interruption. Given that viral transcription is initiated by co-opting of host transcription factors, subtype-specific differences in NF-κB transcription factor binding sites in the Long Terminal Repeats (LTRs) of integrated viral sequences may be differentially inducible in ways that can be targeted for precision cure. It remains unknown if LVR composition (e.g. integration sites and proviral integrity) differ between the most-studied HIV-1B and the most prevalent HIV subtype C (HIV-1C). Likewise, differential responsiveness to NF-κB targeting latency reversal agents (LRAs) – used in “kick-and-kill” cure strategies – has not been examined across subtypes. Taken together, this proposal hypothesizes that HIV-1B and HIV-1C LVR variation drives differential proviral inducibility by NF-κB-targeting LRAs and may inform subtype-specific cure potential. This hypothesis will be addressed through two aims: 1) Defining variation between HIV-1B and HIV-1C LVR composition, and 2) Characterizing subtype-specific LRA reactivation potentials. This project will expand our understanding of HIV subtype-specific biology and address knowledge gaps that could inform HIV cure research. Confirmation of HIV-1C deviation from HIV-1B in either aim represents avenues for novel treatment paradigms, and confirmation of this deviation in both aims suggests that HIV-1C has a smaller and more reactive LVR that would encourage its prioritization for targeted cure efforts. The applicant, Mr. Steven Nadakal, is an MD-PhD student training with the Primary sponsor, Dr. Melissa Smith, an Associate Professor in the Department of Biochemistry and Molecular Genetics (BMG) at the University of Louisville School of Medicine (ULSOM). He is co-sponsored by Dr. Eric Rouchka, a pioneering bioinformatician and Professor in BMG. This work will advance Mr. Nadakal’s conceptual and technical expertise in virology, immunology, bioinformatics, and genomics for use as an infectious disease physician-scientist.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $36,588 )
2026	2026	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	1	6/1/2026	NEW	$36,588
														Subtotal = $36,588

Grand Total All Awards = $36,588

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Comparison of Latent Activation Between Subtypes B and C of HIV

Award Number: F30AI195013

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/29/2026

PERIOD OF PERFORMANCE END DATE: 11/28/2027

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