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What started as a trickle of new antibodies has become a steady downpour. In recent years, researchers have succeeded in isolating large numbers of broadly neutralizing antibodies from chronically HIV-infected individuals. Yesterday, on the opening day of the AIDS Vaccine 2011 conference in Bangkok, Thailand, Ian Wilson of IAVI’s Neutralizing Antibody Center at The Scripps Research Institute presented recently published data on a collection of 17 broadly neutralizing antibodies that he reported are "extremely potent." The collection of new antibodies are 10 times more potent than the recently isolated antibodies and 100 times more potent than the original handful of neutralizing antibodies, including b12, 2G12, and 4E10.

At the first plenary session of AIDS Vaccine 2011, which opened this morning in Bangkok, Thailand, researchers presented the results of a two-year-long effort to try to identify an immunological explanation for the modest 31% efficacy afforded by the prime-boost vaccine regimen tested in the RV144 trial, the first to show any efficacy in protecting against HIV infection. Barton Haynes, who led the scientific steering committee that oversaw the correlates search, reported that two immune responses were found to be significantly correlated with the HIV infection rate in RV144 vaccine recipients, a finding that generated several hypotheses about protective immune responses following vaccination and helped dispel doubts about whether the modest efficacy seen in the trial was real. "The findings lend credence to the vaccine efficacy seen in the RV144 trial," said Haynes, calling the results "intriguing clues on how the RV144 vaccine regimen may have protected."

Could it be that 21st century vaccine technology might eventually eliminate the need for the seasonal flu shot?

The third day of the International AIDS Society's 6th Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) provided more questions than answers. Following the exuberance that greeted Monday's session at which researchers detailed results from one trial showing earlier HIV treatment profoundly (by 96%) reduced HIV transmission rates, and two other trials showing administration of antiretrovirals (ARVs) to HIV-uninfected individuals could protect heterosexual men and women in Africa from acquiring HIV, researchers here were left to tackle the question of what now?

Although there was not much new data on preventive HIV vaccine research presented at the International AIDS Society's 6th Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011), Susan Barnett of Novartis Vaccines did say that researchers would be deciding this week which gp120 proteins to use as a boost in a planned Phase IIb trial in South Africa. This trial is one of several that are being conducted in the wake of the RV144 trial that showed a canarypox vector prime and gp120 protein boost, in that case AIDSVAX, reduced HIV transmission by approximately 31%.

Treatment IS Prevention

Yesterday at the International AIDS Society's 6th Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011), researchers presented overwhelmingly positive results from three studies evaluating the role of antiretrovirals in preventing HIV transmission. These results heralded in a new catch phrase for the field; rather than treatment as prevention, the session was titled "Treatment IS Prevention."

Just days before the International AIDS Society’s (IAS’s) 6th Conference on HIV Pathogenesis, Treatment and Prevention gets underway in Rome, new results were released from two trials showing that oral pre-exposure prophylaxis (PrEP)—the administration of antiretrovirals (ARVs) in an effort to prevent HIV infection—is an effective way to reduce the risk of HIV infection among heterosexual men and women.

Starting this evening, more than 5,000 delegates will gather in Rome for the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Although prevention comes last in the title, it is the topic that will garner the greatest attention at this year's meeting.

Considering how many options have been added recently to the HIV prevention arsenal, is it time to start talking about an endgame?

In advance of today’s World AIDS Vaccine Day, a May 16 symposium sponsored by the New York Academy of Sciences (NYAS) provided an array of talks that largely focused on the progress and challenges in developing an AIDS vaccine. Michael Watson, who leads the global immunization policy group at Sanofi-Pasteur, noted during his opening that HIV scientists have made great strides in recent years, but that we “still don’t fully understand the enemy and how our bodies react to that enemy.”

Oral PrEP Trial in Women Stopped Early

Today, researchers at Family Health International (FHI) announced that they would be closing a trial known as FEM-PrEP that was designed to determine whether oral administration of the antiretroviral (ARV) drug Truvada was able to prevent HIV infection—a strategy known as pre-exposure prophylaxis (PrEP)—ahead of schedule. The trial will be closed early because the trial’s independent data monitoring committee determined during an interim review of the data that it would be highly unlikely that the trial would be able to demonstrate the effectiveness of Truvada even if it continued until its originally planned conclusion.

Today I had a chance to talk to Mario Roederer, a T-cell immunologist at the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases and a co-organizer of the “Protection from HIV” track at the Keystone meeting. He said the goal of the track was “to really expose the vaccine community to the microbicides people and vice versa because these approaches will have to be undertaken together in the future.” Roederer, who is married to microbicide researcher Laurel Lagenaur, said that as microbicides are becoming more specific, they are more similar to vaccines, which is why it is time that vaccinologists and microbicide researchers interact. 

In the last two years, several research groups have reported the isolation of a slew of new broadly neutralizing antibodies (bNAbs) that are more potent than the handful of such antibodies that had been known until then. Among them was VRC01, a bNAb isolated by researchers at the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases, which can neutralize over 90% of currently circulating HIV-1 strains (see Raft of Results Energizes Researchers, IAVI Report, Sep.-Oct. 2009). VRC01 and other HIV-specific bNAbs also have an unusually high degree of affinity maturation, which means that they are quite different from the germline version of the antibody that they are derived from (see Vaccines to Antibodies: Grow Up!, IAVI Report, July-Aug. 2010). 

Three years ago, the Center for HIV/AIDS Vaccine Immunology (CHAVI) began looking at a small cohort of hemophiliacs who had been exposed to HIV but remained uninfected despite receiving Factor VIII concentrates derived from large pools of blood plasma collected from donors, some of whom were infected with HIV (see Individual Armor Against HIV, IAVI Report, July-Aug. 2008).

Even when biomedical interventions against HIV work in clinical trials, as they have lately for several HIV prevention strategies, scientists don’t always know why. To borrow an analogy from the breathtaking backdrop of the annual Keystone conference this week, identifying the correlates of immune protection is a Nordic slog through the wilderness, not an Alpine run.

The antiretrovirals (ARVs) tenofovir and Truvada—a combination of tenofovir and emtricitabine—have received the lion’s share of attention lately for their role in preventing HIV infection, but researchers are experimenting with other ARVs that may also be effective topical pre-exposure prophylaxis (PrEP) agents.

At today's session on lentiviral diversity, Reuben Harris of the University of Minnesota gave an update on his studies of Apobec. In 2002, human Apobec3G was described as a host cell factor that inhibits HIV replication by introducing hypermutations, and HIV has evolved the Vif protein to inhibit Apobec3G by triggering its degradation. Apobec3G can therefore restrict replication of cells with HIV lacking Vif. By now, several additional Apobec3s have been described, but it has been unclear as to which ones contribute to HIV restriction. Harris presented evidence that four Apobec3s, Apobec3D, F, G and H all contribute to HIV restriction. “There is controversy surrounding every single Apobec except for Apobec3G,” Harris said. “So this work should, I hope, resolve that controversy. [We show that] those four are involved, the rest are not involved.”  

It’s probably a good sign when the keynote address on the opening night of a conference is interrupted by fireworks. That’s what happened to Ashley Haase of the University of Minnesota when he was close to the end of his address on HIV transmission on this opening night of the Keystone joint symposia on HIV Evolution, Genomics and Pathogenesis; and on Protection from HIV: Targeted Intervention Strategies, which is taking place from March 20-25 in Whistler, British Columbia. (The fireworks, I am told, take place every Sunday night as part of a “Fire & Ice Show” at the base of the Whistler Village Gondola.) 

It's fair to say that this year's 18th Conference on Retroviruses and Opportunistic Infections (CROI) was dominated by discussion about pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) to prevent HIV infection. This is not all that surprising given that last year two trials demonstrated the first efficacy of PrEP using ARVs in either a pill or topical gel format.

Today's opening plenary presentation by Rochelle Walensky of Harvard Medical School focused on the cost effectiveness of HIV treatment and prevention. She started by defining cost effectiveness as "value for money," which means that a cost-effective strategy does not necessarily imply a cost savings.