US Government Commits More Funding to AIDS
At a World AIDS Day event on Dec. 1 sponsored by Irish rock star Bono’s ONE campaign, US President Barack Obama announced new commitments to controlling and preventing HIV/AIDS worldwide.
Before an audience at George Washington University that included Bono, the singer Alicia Keys, and prominent research figures like US National Institute of Allergy and Infectious Diseases’ director Anthony Fauci, President Obama pledged that by the end of 2013 the President’s Emergency Program for AIDS Relief (PEPFAR) would directly support more than six million people on antiretroviral (ARV) therapy—two million more people than currently receive treatment through PEPFAR—as well as provide ARVs to more than 1.5 million HIV-infected pregnant women. The US will also support more than 4.7 million adult voluntary medical male circumcisions to prevent HIV infection in Eastern and Southern Africa over the next two years, the President said.
Globally, thanks to all HIV treatment programs, nearly 50% of those eligible for treatment are receiving ARVs. “We are winning this fight,” Obama said. “But the fight is not over, not by a long shot.”
Domestically, the Obama administration has also promised to increase funding by US$35 million to help cash-strapped state AIDS Drug Assistance Programs (ADAPs) provide ARVs to 3,000 HIV-infected individuals. Obama did not specify how these initiatives would be funded, but he suggested that continuing to focus on lowering both the purchase price and cost of delivering ARVs would help cover the additional costs.
Obama’s remarks came on the heels of a new round of data from the Joint United Nations Programme on HIV/AIDS showing that while the number of new infections held steady from 2009 to 2010, the global incidence has declined by more than 21% since 1997, driven by declines in many sub-Saharan nations. However, HIV incidence in the US and Europe has remained static over the same time period while new cases have surged 23% in Eastern Europe and Central Asia since 2008.
AIDS advocates applauded Obama’s announcements, especially given the current economic environment. In November, the Global Fund to Fight AIDS, Tuberculosis and Malaria, which accounts for about a quarter of international financing for HIV/AIDS, announced that it wouldn’t be making new grants because it has only secured enough funding to sustain ongoing programs through 2013. —Regina McEnery
Researchers Characterize Target of Broadly Neutralizing Antibody PG9
Following the isolation of dozens of broadly neutralizing antibodies (bNAbs) from HIV-infected individuals, the focus has shifted to characterizing the epitopes on HIV that are targeted by these antibodies. Most recently, a study led by Peter Kwong, chief of the structural biology section at the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases, provided an atomic-level description of the epitope on the first and second variable loops known as V1 and V2 that form part of the glycan shield of HIV Envelope that is targeted by the bNAb PG9 (1).
The V1/V2 portion of gp120 is targeted by a number of the recently isolated bNAbs. However, strategies used to determine the structure of other portions of HIV gp120 were unsuccessful in providing a crystal structure of this important region.
To successfully get the structure of V1/V2 this time, researchers placed the
V1/V2 sequences (amino acid residues 126-196) into two protein scaffolds and then crystallized the scaffolds in complex with PG9. These crystals were then used to study at an atomic level the interactions between PG9 and V1/V2. Researchers found that PG9 grasps a specific glycan at amino acid residue 160, forming an extensive interaction that is critical for PG9 binding. Other interactions with PG9 occur at another glycan at residue 156 or residue 170 in the second scaffold, though these are not necessary for PG9 recognition. Additionally, a strand in the CDR H3 region of PG9 interacts through hydrogen bonding with the most variable strand of amino acids in V1/V2 known as strand C. Together with a minor interaction with strand B and the B-C connecting loop of V1/V2, these interactions complete the PG9 epitope.
This epitope is less complex than those of other antibodies, suggesting it may be easier to design and present an immunogen based on it. However, the glycosylation at residue 160, which is necessary for PG9 binding, is not always present in transmitted founder viruses, developing only through the process of immune selection, according to some studies.
Researchers note that there is now more interest in the V1/V2 region, given that the recent correlates of risk analysis from the RV144 trial in Thailand suggested that antibodies targeting this site were associated with a reduced risk of HIV infection (see A Bangkok Surprise, IAVI Report, Sep.-Oct. 2011). The study’s authors write that, “it is fascinating that the V1/V2 domain—which functions in evading antibody-mediated neutralization—is itself a site of effective neutralization.” —Kristen Jill Kresge
1. Nature 480, 336, 2011