This was the first consistent demonstration of post-treatment immune control in monkeys infected with SIV, without previous vaccination. Long-term post-treatment control of HIV has been reported in only a handful of people treated soon after infection. To learn more, check out these links.
Transient SIVmac remission induced by TLR7 agonist, reported at 2016 CROI conference
Immune control of SIVagm, no antiretroviral drugs necessary. Model of “elite controllers.”
Immune clearance of SIVmac; prior CMV-based vaccination necessary.
Post-treatment control of HIV – VISCONTI study. Roundup of HIV remission cases, from Treatment Action Group. Read more
HIV researchers are becoming increasingly bold about using the “cure” word in reference to HIV/AIDS, even though nobody has been cured besides the “Berlin patient,” Timothy Brown, who had a fortuitous combination of hematopoetic stem cell transplant from a genetically HIV-resistant donor. Sometimes researchers use the term “functional cure,” meaning under control without drugs, to be distinct from “sterilizing cure” or “eradication,” meaning the virus is gone from the body. A substantial obstacle is that HIV integrates into the DNA of some white blood cells.
HIV cure research is part of the $35.6 million, five-year grant recently awarded by the National Institutes of Health to Yerkes/Emory Vaccine Center/Emory Center for AIDS Research. Using the “shock and kill” approach during antiviral drug therapy, researchers will force HIV (or its stand-in in non-human primate research, SIV) to come out of hiding from its reservoirs in the body. The team plans to test novel “latency reversing agents” and then combine the best one with immunotherapeutic drugs, such as PD-1 blockers, and therapeutic vaccines.
The NIH also recently announced a cluster of six HIV cure-oriented grants, named for activist Martin Delaney, to teams led from George Washington University, University of California, San Francisco, Fred Hutchinson Cancer Research Center, Wistar Institute, Philadelphia, Beth Israel Deaconess Medical Center and University of North Carolina. Skimming through the other teams’ research plans, it’s interesting to see the varying degrees of emphasis on “shock and kill”/HIV latency, enhancing the immune response, hematopoetic stem cell transplant/adoptive transfer and gene editing weaponry vs HIV itself.
I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes aÂ treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day.Â One of the goals of their IL-21 treatment is to restoreÂ intestinal Th17 cells, which are depleted by viral infection.Â In this context, IL-21’s effect is anti-inflammatory.
However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examinesÂ Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, bothÂ an inexpensive blood pressure medication and a drugÂ under development for psoriasisÂ seem to do just that.
Note for microbiome fans: connections between Th17 cells and intestinalÂ microbes (segmented filamentous bacteria) are strengthening. It gets complicated because gut microbiota, together with Th17 cells, mayÂ influenceÂ metabolic disease and Th17-like cells are also in the skin — location matters.
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
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
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
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 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 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.