This week, researchers from Yerkes and Emory Vaccine Center led by Cindy Derdeyn published a paper that I first thought was disturbing. It describes how monkeys vaccinated against HIV’s relative SIV (simian immunodeficiency virus) still become infected when challenged with the virus. Moreover, it’s not clear whetherÂ the vaccine-induced antibodies are exerting any selective pressure on the virus that gets through.
But then I realized that this might beÂ an example of “burying the lead,” since we haven’t made a big hoopla about the underlying vaccineÂ studies, conducted by Rama Amara. Some of these studiesÂ showed that a majority of monkeys can beÂ protected from repeated viral challenge.Â TheÂ more effective vaccine regimens include adjuvants such asÂ the immune-stimulating molecules GM-CSF or CD40LÂ (links are the papers on the protective effects). Read more
Virologists at Emory, Yerkes and Childrenâ€™s Healthcare of Atlanta have uncovered a critical detail explaining how HIV assembles its infectious yet stealthy clothing.
Paul Spearman, MD
For HIV to spread from cell to cell, the viral envelope protein needs to become incorporated into viral particles as they emerge from an infected cell. Researchers led by Paul Spearman have found that a small section of the envelope protein, located on its “tail”, is necessary for the protein to be sorted into viral particles.
The results were published June 1 inÂ Proceedings of the National Academy of Sciences. Read more
The third winner of the Best Image contest from the Postdoctoral Research Symposium, from postdoc Joshua Strauss in electron microscopist Elizabeth Wrightâ€™s lab.
Tetherin is a host cell factor that mechanically links HIV-1 to the plasma membrane. This is the first time anyone has imaged tethered HIV-1 by cryo-electron tomography. In doing so, we were able to learn about the length and arrangement of the tethers.
Note: Tetherin also studied by Paul Spearman + colleagues.
Cryo-electron tomography is an imaging technique which enables scientists to look at biological specimens in a â€œnative-likeâ€ (frozen hydrated) state, without the chemical fixatives or heavy metal stains typically used for conventional electron microscopy.
The 3D reconstruction was manually segmented to highlight the different viral and cellular components: HIV-1 virions (lavender), mature conical-cores (aqua blue), immature Gag lattice (pink), plasma membrane (peach), rod-like tethers (sea green).
Drug discovery veteran Dennis Liotta and his team continue to look for ways to fight against HIV. Working with pharmaceutical industry colleagues, he and graduate student Anthony ProsserÂ have discovered compounds that are active against three different targets: immune cells’Â entry gates for the virus (CCR5 and CXCR4), and the replication enzyme reverse transcriptase. That’s like one arrow hitting three bulls eyes. AnÂ advantage for these compounds: it could be less likely for viral resistance to develop.
For more, please go toÂ the American Chemical Society — there will be a press conference from the ACS meeting in Denver on Monday, and live YouTube.
What conferences likeÂ the HIV + Aging meeting recently held byÂ Emory in Decatur offer the visiting writer: anecdotes that illustrate issuesÂ of clinical care.
To illustrate her point that assumptions about who is likely to develop a new HIV infection may lead doctors to miss possible diagnoses, keynote speaker Amy Justice from Yale described a patient who was seen last year at Yale-New Haven Hospital.
AÂ 60 year old man reported fatigue and had lost 40 pounds over the course of a year. Despite those symptoms, and the discovery of fungal and viral infections commonlyÂ linked to HIV/AIDS, it took nine months before a HIV test wasÂ performed on the patient, a delay Justice deplored.
Sex and substance abuse do not end at age 50, she said, citing data showing that the risk of HIV transmission can be greater among older adults, and that substance abuse is more likely among adults who are HIV positive compared to those who are HIV negative.
Justice also highlighted the issue of polypharmacy (interactions betweenÂ prescription drugs at the same time), a concern even inÂ peopleÂ who are not living with HIV. Common blood pressure medications taken by older adults to prevent heart disease have been suspected of increasing the risk for falls. That’s a problem especially for people living with HIV, because HIV infection has been linked to weakened bone. Read more
Yerkes immunologist Guido Silvestri and colleagues have a paper in PLOS PathogensÂ shedding light on the still singular example of Timothy Brown, aka “the Berlin patient”, the only human cured of HIV. Hat tip to Jon Cohen of Science, who has a great explanatory article.
Recall that Brown had lived with HIV for several years, controlling it with antiretroviral drugs, before developing acute myeloid leukemia. In Berlin, as treatment for the leukemia, heÂ received aÂ bone marrow transplant — and not just from any donor; the donor had a HIV-resistance mutation. What was the critical ingredient that enabled HIV to beÂ purged from his body?
Conditioning: the chemotherapy/radiation treatment that eliminates the recipient’sÂ immune system before transplant? HIV-resistant donorÂ cells? Or graft-vs-host disease: the new immune system attacking theÂ old?
Silvestri and colleagues performed experiments with SHIV-infected non-human primates that duplicate most, but not all, of the elements of Brown’s odyssey. The results demonstrate that conditioning, by itself, does not eliminate the virus from the body. But in one animal, it came close.Â Frustratingly, that animal’s kidneys failed and researchers had to euthanize it. In two others, the virus came back after transplant.
A critical difference from Brown’s experience is thatÂ monkeys received their own virus-free blood-forming stem cells instead of virus-resistant cells. Cohen reports thatÂ Silvestri hopes to do future monkey experiments that test more of these variables, including transplanting the animals with viral-resistant blood cells that mimic the ones that Brown received.Â
Does hormonal contraception increase the risk for a woman to acquire HIV from an infected partner?
This topic, with implications for public health in countries where HIV risk is high, has been contentious. Some previous studies had found the answer to be yes, for methods involving injectable progesterone such as Depo-Provera. This led the World Health Organization in 2012 to advise women using progesterone-only injections to use condoms to prevent HIV infection.
At the recent AIDS 2014 meeting in Australia, Emory epidemiologist Kristin Wall presented data from public health programs in Zambia. This is another study emerging from the Zambia-Emory HIV Research Project directed by Susan Allen.
Wall’s presentation is available here.
Studying 1393 heterosexual couples with a HIV-positive male partner over 17 years, Wall and her colleagues found no significant difference in incidence rate per 100 couple years between hormonal and non-hormonal forms of contraception. Read more
In the HIV/AIDS arena, theÂ idea of “treatment as prevention” has been gaining strength. Multiple studies have shown that treatment with anti-retroviral drugs can dramatically reduceÂ the likelihood that someone infected with HIV will be able to pass the virus to someone else.
However, a recentÂ strategy documentÂ for HIV/AIDS prevention developed byÂ aÂ International Antiviral Societyâ€“USAÂ panel, co-led by Rollins Global Health chair Carlos Del Rio, puts biomedical interventions hand in hand with psychosocial measures such as couples counseling and treatment for drug dependence.
Why? Because people everywhere can have trouble sticking to antiretroviralÂ treatment, even if drugs are available. And couples counseling by itself is valuable.
A powerful example of how this plays out, and of the importance of couples counseling to the effectiveness of antiretroviral drugs in prevention, comes fromÂ a recent presentation fromÂ Emory epidemiologist Kristin Wall at the AIDS 2014 meeting in Australia. The website NAM AidsmapÂ had a helpful write-up of her presentation, which isÂ available here.Â Thanks to co-author Susan Allen for alerting us to this.
CVCT (couples voluntary counseling and treatment) greatly enhanced the preventive effect of antiretroviral treatment, when compared to treatment without counselling, Wall’sÂ analysis of a large cohort of couplesÂ in Zambia showed.Â
Update: Allen points out that couples counselingÂ by itselfÂ was effective in helping people avoid HIV, with a 75 percent reduction in incidence for couples where the HIV+ partner was not receiving antiviral therapy or with HIV negative couples.Â Read more
On Thursday, NPR had a nicely done story on discordant couples (one partner is HIV positive, the other is HIV negative) in Kenya.
It provided a reminder of Susan Allen’s work in Rwanda and Zambia with discordant couples. It also very simply laid out the policy issues connected with treating discordant couples:
Medical workers are http://www.raybani.com/ extremely interested in discordant couples for two reasons. One is that almost half of new infections in Kenya happen in these relationships. It’s one place where HIV is spreading.Â The second reason is that when couples are open with each other about their HIV status, managing HIV is more successful…
The World Health Organization now recommends that any HIV-positive individual in a discordant relationship be supplied HIV treatment.Â But discordant couples are still being treated on an ad hoc basis in Kenya, primarily because the funding for the medication just isn’t there.
Allen’s research provided critical data about HIV Ray Ban outlet transmission and prevention methods, and led to the adoption of the WHO guidelines mentioned in the story.Â She has said that the WHO guidelines were designed to help partners in a stable relationship work together to prevent the uninfected person from getting the virus and that low-tech, inexpensive prevention methods like condoms are just as important as antiretroviral therapy in this effort.
Emory Vaccine Center director Rafi Ahmed, is a co-author on a recent Science paper advocating a â€œHuman Vaccines Projectâ€. Wayne Koff, chief scientific officer of IAVI (International Aids Vaccine Initiative) is lead author and several other vaccine experts are co-authors.
The idea behind a â€œHuman Vaccine Projectâ€ is to combine efforts at developing vaccines for major (but very different) diseases such as influenza, dengue, HIV, hepatitis C, tuberculosis and malaria, with the rationale that what scientists working on those diseases have in common is the Ray Ban outlet challenge of working with the human immune system.
Technology has advanced to the point where whole genome-type approaches can be brought to bear on vaccine problems. The authors cite work by Bali Pulendranâ€™s laboratory on â€œsystems vaccinologyâ€ and their analysis of the yellow fever vaccine as an example.
One major puzzle confronting vaccine designers is to coax the immune system into producing broadly neutralizing antibodies against a rapidly mutating virus, whether it is Gafas Ray Ban outlet influenza or HIV. Our own Cynthia Derdeyn has been analyzing this problem through painstaking work following how the immune system pursues a twisting and turning HIV.
An interesting related tidbit:
There are hints that the reverse engineering of vaccines has taken a leap forward in the case of RSV (respiratory syncytial virus): Scientists at Scripps Research Institute have designed vaccine components by computer and have used them to provoke neutralizing antibodies in monkeys.
Also check out Mike Kingâ€™s feature in Emory Health on HIV vaccine research.