The 17th annual CROI took place last week in San
Francisco. For the first time this year, poster discussion sessions are also included
in the conference webcasts, meaning that essentially the entire content of the
meeting can be accessed online. Several media outlets also provided wide-ranging coverage and interviews during CROI, including AIDSMeds.com, The Body and AIDSMap.
There was no single study that dominated the
headlines, but several emerging themes in HIV research were reinforced by new
data. Chief among them, the idea that increased uptake of antiretroviral
therapy (ART) and a greater degree of viral suppression at the community level
might reduce new HIV diagnoses received preliminary support in an analysis by Dr.
Moupali Das-Douglas from the San Francisco Department of Health. The
presentation is the first in the Testing and Transmission session at 9:30am on Wednesday. More direct evidence came from the partners
in prevention trial, which enrolled 3,408 discordant couples in order to assess
the impact of suppressing HSV-2 with acyclovir on HIV transmission. While
acyclovir had no effect, an analysis presented at CROI (paper #136) revealed that among
HIV positive partners on ART, there was one transmission of HIV to the
uninfected partner, which occurred within the first 18 days of ART initiation.
Among couples where the HIV positive partner was not on ART, there were 102 HIV
transmissions.
In terms of the intersection of HIV pathogenesis and
clinical care, a group of researchers at UCSF presented a suite of studies
showing that markers of inflammation, immune activation and immunosenescence
correlate with a wide spectrum of adverse phenomena that clinician scientist
Steve Deeks groups under the umbrella term “badness.” Examples include measures
of arterial health such as the presence of plaques and reduced arterial
distensibility. Priscilla Hsue summarized some of these findings in an insightful talk on
HIV and cardiovascular health (the webcast is the third presentation in the Symposium on Pathogenesis and Clinical Management of Complications at 4pm on
Wednesday 2/17).
After many years of often contentious debate, the idea that
HIV replication is completely stopped in the majority of people on suppressive
ART therapy finally seemed to gain acceptance at the 2010 CROI. The use of an
assay developed by Sarah Palmer that can measure down to 0.2 copies of HIV RNA
in peripheral blood has played a key role; many studies – including several
presented at CROI – have now shown that intensifying ART has no effect on the
residual HIV RNA that is below the range of standard viral load tests (which can’t
measure less than 50 copies per ml of blood), but detectable using Palmer’s
technique. These findings have led to a general consensus that, in most cases,
the low-level HIV RNA (<50 copies) that can sometimes be detected in people
on ART is being produced by long-lived cells containing integrated HIV DNA.
These long-lived reservoirs can occasionally pump out new viruses, but ART
prevents them from going on to infect new cells. As described in a talk by
Frank Malderelli from the National Cancer Institute, this new understanding of
HIV persistence is reinvigorating efforts to extinguish the remaining embers of
infection and fully cure HIV. Malderelli’s talk is the first in the The Future of HIV Therapeutic Research Symposium on Friday 2/19, the last
session listed on the Friday webcast page.
Other selected presentations that may be of interest, with brief comments on each:
Plenary (webcast): Pathogenic vs Nonpathogenic Retrovirus Infections
Guido Silvestri
Univ of Pennsylvania, Philadelphia, US
– Excellent review of the state of the science and
particularly on the crucial role of persistent immune activation in
distinguishing pathogenic from non-pathogenic immunodeficiency virus
infections. Also offers this quote (from Guido Silvestri & Steve Deeks),
which may turn out to be a harbinger of where HIV pathogenesis research is
headed now that fully suppressive ART regimens have become available: “In the absence
of HIV replication, residual inflammation rather than drug toxicity may be the
most important obstacle towards reaching a normal healthy human lifespan.”
Paper # 82
S Jung, H Wend, N Donhauser, K Eissmann, B Fleckenstein, and
Heide Reil*
Univ Hosp Erlangen, Germany
Webcast, Thursday 2/18 (last presentation in session)
– Reports that some antibodies against the E2
protein of GB virus C (GBV-C) can broadly neutralize HIV isolates, due to a
mechanism involving interactions with phospholipids in the lipid bilayer of the
virus (a coating acquired from the host cell during virus budding). A similar
mechanism has been reported for the broadly neutralizing monoclonal antibody
2F5 and these findings may open novel routes toward an effectve neutralizing
antibody-based HIV vaccine. This presentation is also cited on JBM's PS blog which is
focused on developments in this field of study.
Paper # 140
Barbara Felber*1, E-Y Kim2, R Pal3, R Desrosiers4, S
Wolinsky2, and G Pavlakis1
1NCI-Frederick, MD, US; 2Northwestern Univ, Chicago, IL, US;
3Advanced Biosci Labs, Inc, Kensington, MD, US; and 4New England Primate Res
Ctr, Boston, MA, US
Webcast, Friday 2/19 (last but one presentation in session)
– Uses challenge with a diverse SIVmac251 stock
and finds that some variants present in the stock remain undetectable until
chronic infection. This calls into question the interpretation that a single
dominant virus detectable during acute HIV infection means that only a single
variant was transmitted.
Paper # 285
Maraviroc Intensification for Suboptimal CD4+ Cell Response
Despite Sustained Virologic Suppression: ACTG 5256
Timothy Wilkin1, C Lalama2, A Tenorio3, A Landay3, H
Ribaudo2, J McKinnon4, R Gandhi5, J Mellors4, J Currier6, and R Gulick1
1Weill Cornell Med Coll, New York, NY, US; 2Harvard Sch of
Publ Hlth, Boston, MA, US; 3Rush Univ Med Ctr, Chicago, IL, US; 4Univ of
Pittsburgh Sch of Med, PA, US; 5Massachusetts Gen Hosp, Boston, US; and 6Univ
of California, Los Angeles, US
Poster PDF: http://www.retroconference.org/2010/PDFs/285.pdf
– Adding Maraviroc did not increase CD4 T cell
counts in people with poor CD4 T cell recovery despite sustained viral load
suppression. There was, however, a statistically significant reduction in
measures of immune activation; one interpretation of these findings is that –
at least in some cases – persistent immune activation may be a consequence of
poor CD4 T cell recovery rather than the primary cause. These results may note
bode well for the four other ongoing clinical trials of maraviroc with similar designs.
Paper # 714
Steven van Lelyveld*1, L Gras2, A Kesselring2, S Zhang2, F
de Wolf2, A Wensing1, and A Hoepelman1
1Univ Med Ctr Utrecht, The Netherlands and 2Stichting HIV
Monitoring, Amsterdam, The Netherlands
Poster PDF: http://www.retroconference.org/2010/PDFs/714.pdf
– A study showing that poor immune recovery
despite suppression of viral load is a risk factor for clinical illness,
emphasizing the need to research and develop new therapies to promote immune
reconstitution for people in this situation.
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