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.
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.
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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