"viral and latent HIV reservoir characteristics in HIV patients with persistent low-level viremia

Ended Project Grant Awarded Last action

Award ID
R21AI174880
Recipient
Awarding agency
Obligated
$438,401

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date
Place of performance
Ghana

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The success of antiretroviral therapy (art) is usually measured by the proportion of persons living with HIV (PLWH) who are virologically suppressed on art. However, the standards used to determine viral suppression differ between the developed and the developing world. The developed countries define viral suppression as viral load (VL) less than 50 copies per ML, while most of africa, accepts the world health organization (who) prescribed less than 1000 copies per ML as viral suppression in resource-limited settings (RLS). This has created a category of persons in RLS with persistently low-level viremia (PLLV) of 50-999 copies/ML who are lumped together with the truly virologically suppressed, and thus not given much attention. Since viral replication continues during low-level viremia, this may fuel the proliferation of resistance mutations, expand the diversity of viral strains and increase the viral reservoir size in those with PLLV. However, whether this population has more diverse viral strains, has a larger reservoir size or serve as a source of the current rise in drug resistance in africa has not been studied. This creates a critical knowledge GAP which if not filled could derail the success of art and serve as a bottleneck in HIV cure efforts in africa. Our working hypothesis is that art-treated PLWH with persistent low-level viremia have greater virus diversity, larger reservoir size and select for drug resistance mutations. We intend to investigate this hypothesis with two specific aims: aim 1: determine viral diversity and drug resistance mutations among patients with PLLV. We hypothesize that continuous viral replication during low-level viremia on art expands the diversity of viral strains and fuel the emergence of drug resistance mutations. First, we will perform a cross-sectional evaluation to determine the frequency of clinically-relevant drug resistance mutations in those with PLLV. Second, we will follow the patients with PLLV for 18 months to determine resistance evolution and the proportion of those who break through to VL>1000. Third, we will determine inter- and intra-patient genetic diversity of HIV in those with PLLV. Aim 2: determine the characteristics of the HIV reservoir in HIV patients with PLLV. We hypothesize that persistent low viremia feeds the latent reservoir making IT larger and more diverse in those with PLLV compared to the truly suppressed persons. The question here is whether PLLV enlarge the size of the reservoir and increase clonal expansion. If that were the case, IT would become more urgent to bring the virus to undetectable in these patients. The knowledge gained will be useful for our HIV control programs; may call for changes in treatment guidelines in ghana and africa and prompt more extensive studies among persons with persistent low viremia in resource- limited settings.

Transactions

Action Obligated Date
Amendment $0
Amendment $142,569
Amendment $147,916
Original award $147,916

Quick answers

Who received award R21AI174880?

R21AI174880 was awarded to Noguchi Memorial Institute For Medical Research by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 1, 2023.

How much is award R21AI174880 worth?

$438,401 has been obligated on R21AI174880.

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