February 27, 2014
It's that time of the year again. Like a circadian rhythm, cold, gray skies remind me of winter days working in a Russian HIV hospital, but my internal clock also says that it's time for the Conference on Retroviruses and Opportunistic Infections (CROI). Like most years, it seems, this year's meeting takes place in Boston, where the polar vortex meets university learning.
But while it might be cold outside, CROI is the meeting for presentation of the hottest scientific findings on HIV topics.
What are the topics that I expect will heat things up this year?
A new era in the treatment and cure of hepatitis C is upon us. With last year's U.S. Food and Drug Administration (FDA) approval of sofosbuvir (Sovaldi), a time in which short-course, interferon-free, curative treatment for most people living with HCV (and HCV/HIV coinfection) has become possible. Indeed, if we successfully diagnose and link to care people living with HCV, we can begin to imagine control of the HCV epidemic.
CROI will start off with an HCV bang, with several presentations highlighting data on recently approved and investigational medications in studies with names even catchier than most HIV studies, including PEARL (a study of combination therapy with Abbvie's investigational HCV medications), SYNERGY and PHOTON (a study of sofosbuvir in an all-oral regimen with ribavirin in coinfected persons). Other studies will also point to the potential of all-oral, interferon-free treatments.
So, we've got good drugs to treat HIV. But which drugs should we use? And can we break free of the mantra that we must always prescribe two nukes plus a third drug? How about very long-acting, injectable regimens -- can they be viable?
Just last year, we learned that in two large clinical studies, the integrase inhibitor dolutegravir (Tivicay) was superior to officially recommended regimens using either the industry behemoth efavirenz (Sustiva, Stocrin) or boosted darunavir (Prezista). Those official recommendations -- the U.S. Department of Health and Human Services' (DHHS) expert panel guidelines regarding antiretroviral therapy in adults and adolescents -- ultimately went on to add regimens containing dolutegravir and elvitegravir (another integrase inhibitor, part of the four-in-one drug Stribild) to its elite "preferred" status for first-line treatment, alongside raltegravir-containing regimens. Together, these developments suggest that the standard of care and side effect burden of current treatments may be evolving for the better.
At this year's CROI, we'll learn from AIDS Clinical Trials Group researchers the results of ACTG 5257, a massive NNRTI-sparing study involving first-line treatment with tenofovir/emtricitabine (Truvada), in which patients were randomly assigned to receive that drug along with boosted atazanavir (Reyataz), boosted darunavir or raltegravir. I'm told the results are going to have blockbuster importance.
Similarly, I'm looking forward to seeing results of the NEAT001 study -- a huge, non-industry sponsored study comparing the nuke-sparing regimen of raltegravir and boosted darunavir to the conventional (and DHHS-preferred) regimen of tenofovir/emtricitabine and boosted darunavir. The authors are expected to report that the nuke-sparing regimen is non-inferior.
Since we first learned about the prospect of once-monthly (or even longer) injectable treatments for HIV, many of us in the clinical field have been at the edge of our seats looking for more data about the utility of these medications for pre-exposure prophylaxis (PrEP), or -- more importantly, in my opinion -- for the treatment of established HIV infection. It looks like we'll get some at CROI.
Investigators from the U.S. Centers for Disease Control and Prevention (CDC) will present data that are likely to show that monthly injections with the investigational integrase inhibitor GSK744 protects macaques from repeated vaginal exposure to simian-human immunodeficiency virus (SHIV). These data, combined with previous data showing effectiveness in prevention despite repeated rectal exposure of SHIV in monkeys, suggest the opportunity to use 744 for PrEP in people.
744 is also being studied as a possible treatment for people living with HIV. The central dilemma to its further development is the need to find other long-acting medications to partner with the drug. Investigators from GlaxoSmithKline will present data from the LATTE study, in which oral 744 is partnered with rilpivirine (another long-acting medication candidate) in a novel, two-drug maintenance regimen. This is a required research stepping stone to developing what we can only hope will become a combination, long-acting, injectable regimen.
Last year at this conference we refocused the world's attention to prevention of mother-to-child transmission (PMTCT) of HIV with the remarkable investigation of the so-called "Mississippi baby" -- a case of apparent HIV cure after very early initiation of combination HIV treatment in a newborn infant.
On March 5, we'll hear more from one of the Mississippi case's investigators, who will give a presentation with the intriguing title suggesting that there might be other "cures." The title reads (emphasis mine): "Very early combination ART in perinatal HIV infection: two case studies."
In more down-to-earth research, lopinavir/ritonavir (Kaletra) may be a declining medication for HIV treatment here in the U.S., but two studies on PMTCT will challenge our standards regarding PMTCT regimens used elsewhere in the world -- or at least in Africa. Comparative studies will be presented on lopinavir/ritonavir versus efavirenz in pregnant and breast-feeding women from Uganda, as well as on use of lopinavir/ritonavir versus lamivudine in infants from Zambia.
With the average age of people living with HIV in the U.S. approaching 50, there has been growing attention to issues related to healthy aging with HIV. Osteoporosis and fracture risk is one of many areas of concern.
A few years ago, the CDC HIV Outpatient Study (HOPS) presented data at CROI that concluded HIV-positive people were much more likely to experience bone fractures than age- and gender-matched HIV-negative people. At this CROI, Linda Battalora (who, I am proud to say, is my graduate student) will present additional data from HOPS and its sister study, SUN, which are expected to show that in a large population of mostly younger adults (under the age of 50), the presence of osteoporosis at baseline was associated with a new bone break more so than among those with normal bone density at baseline. A separate study is expected to show that the commonly used FRAX risk calculator underestimates fracture risk in the HIV population.
Incidentally, related to both this and the previous subject: Although the effectiveness of antiretrovirals in PMTCT is well established, much debate still centers on the safety of antiretrovirals in pregnancy. As a bone health researcher myself, I'll be interested in the results of a study from the National Institutes of Health that are expected to show lower bone mineral density among babies born to mothers treated with tenofovir DF (Viread), a drug associated with increased risk of bone mineral loss.
Increased, early access to HIV medications is dramatically reducing HIV transmission in many places, including my clinical home base of Denver . Yet significant disparities in accessing care and staying engaged in care exist, and they pose challenges to our ability to deliver on the promise of an AIDS-free generation in our lifetime. Several key reports at CROI will chronicle disparities in access to care and viral suppression in HIV hot spots throughout the world, including New York City, Washington, D.C., and sub-Saharan Africa.
Last year, I suggested that CROI was evolving to be less about new drugs and new disease and more about long life, hepatitis and prevention. CROI 2014 will be no different, but the pace of discovery in these new territories is accelerating. While it likely will be arctic outside the Boston conference center, these presentations will be the fuel that will generate warm discussions and a brighter future for all living with and affected by HIV.
Benjamin Young, M.D., Ph.D., is vice president and chief medical officer of the International Association of Providers of AIDS Care based in Washington, D.C., and an adjunct professor at the Josef Korbel School of International Studies at the University of Denver. Dr. Young has received consulting or speaking fees from Bristol-Myers Squibb, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Merck & Co., Monogram Biosciences, and ViiV Healthcare. He has received research funding from Bristol-Myers Squibb Company, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Merck & Co., and ViiV Healthcare.
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