Page 164 - HA Convention 2015

Parallel Sessions

PS2.3 Controlling AIDS 10:45 Theatre 2

Tuesday, 19 May Biomedical Prevention and Possible Cure of HIV/AIDS
Chen ZW
AIDS Institute; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong

Although antiretroviral therapy (ART) helps control HIV disease progression and reduces the chance of viral transmission (e.g.
treatment as prevention), AIDS pandemic still grows with over two million new infections each year. From 2011 to 2014, Hong
Kong had four historical high records of annual infections. To date, evidence of vaccine-elicited CD8 T cells in protection
or even eradication against AIDS viruses in non-human primate models and immune control of HIV-1 in humans under
certain circumstances (e.g. elite controllers), provide a strong rationale to continue the pursuit of an effective vaccine-based
immunotherapy to eliminate AIDS in an active way.

In our study, we aim to determine active vaccination for elimination (AV4E) of AIDS using a newly discovered PD1-based HIV
vaccine strategy. In animal models, we found that active PD1-based DNA vaccinations resulted in a significant reduction
of viral latency, which was mediated primarily and dose-dependently by vaccine-elicited CD8+ T cells. These effector cells
highly express T-bet and Eomes, and functioned by releasing inflammatory IFN- and TNF- in the vicinity of target cells, which
may trigger TRAIL-directed cell apoptosis. Importantly, repeated DNA vaccinations, a major advantage over live-vectored
vaccines, eliminated immune suppressive cells, with the frequency of Gag-specific CD8+ T cells inversely correlating with the
number of target cells. Our results, therefore, support clinical development of PD1-based DNA vaccination in immunotherapy
of HIV-infected patients. With sustained efforts in HIV/AIDS research, therefore, it is possible to discover an effective AIDS
vaccine or a therapeutic cure. (We thank sincerely HK-RGC762712, CRF-HKU5/CRF/13G, ITS/194/13, PCFB, ATF and HKU-
UDF for funding).

PS2.4 Controlling AIDS 10:45 Theatre 2

HOSPITAL AUTHORITY CONVENTION 2015 The Implication of Viral Load Measurement at Population Level in the Epidemiologic Control of HIV
Lee SS
Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong

When the first antiretroviral compound was put into use in the late 1980s, few had expected it to make significant impacts.
Today highly active antiretroviral therapy (HAART) is the gold standard in clinical HIV management. Clinical effectiveness
aside, the public health dimensions of HAART are surfacing in recent years. The multi-centre trial HPTN052 provided
evidence that early treatment of HIV infection could minimise virus transmission to one’s uninfected sex partners. The study
has therefore extended the concept of HIV therapy from clinical management to prevention. Is “treatment-as-prevention”
(TasP) a brand new strategy? When HIV/AIDS was first discovered in Hong Kong, one of the earliest responses was the
setting up of a clinical service for managing infected patients. While HAART was not available, other measures were
introduced to improve the health status of HIV positive patients. Even these therapies have not targeted HIV virus specifically,
they contribute to the prevention of HIV-associated complications with resultant morbidity benefits.

With the expanded application of HAART, the current range of epidemiologic measures like incidence and prevalence are
becoming insufficient for monitoring the impacts of TasP strategy. For patients who have been receiving HAART, plasma
viral load is a routine test to confirm the efficacy of the therapy. At population level, individual viral load measures can be
summated in different ways to reflect the impacts of HAART to the population. New indices that have been introduced
are monitored, in-care, community and population viral load. Using data collected from all clinical HIV services in Hong
Kong in the last decade, it can be seen that population level viral load measures have been falling ever since HAART was
implemented as a standard therapy. The trajectory however varies between community groups. With the good coverage
of HAART, monitored or in-care viral load can be translated into a new surveillance marker for monitoring the local HIV
epidemic. Mathematical modelling is an indispensable approach if population viral load is adopted for epidemiological
monitoring. To further realise the goal of TasP, the next target should be expanded HIV testing. To date, a proportion of HIV
infected individuals remain undiagnosed, and they will function as the source of on-going virus transmission. With the proven
effectiveness of a biomedical model for HIV prevention, hospital services could and should play an increasingly important
role of achieving prevention, by delivering early diagnosis. Its effectiveness can again be assessed by measuring viral load at
population level.

162