PROJECT SUMMARY
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.
