CROI 2013: The beat goes on — progress in HIV, HCV infections
The 2013 Conference on Retroviruses and Opportunistic Infections addressed research in viruses beyond the HIV retrovirus and had little new information on opportunistic infections. The audience did not object. CROI came to a chilly Atlanta to hold its 20th Annual Meeting in the city that is home to the CDC and the site of the first International AIDS Conference in 1985. Appropriately, prevention was a strong theme of CROI this year, and the distance we’ve traveled since 1985 was striking in discussions of a possible second case of HIV cure and in the very real cures of hepatitis C virus infection — a virus not yet identified in 1985.
HIV cure in infant
Researchers from the University of Mississippi, Johns Hopkins University and others reported prolonged HIV negativity (by antigen and antibody tests) in an infant treated at birth. The infant’s mother was HIV-infected but untreated, and after a precipitous labor, the child was tested and also viremic. The infant was immediately treated with a nevirapine-based regimen but was lost to follow-up, and the mother stopped therapy after 18 months. When, after about 6 months, the infant was retested, she was negative for HIV by ultrasensitive assays and also was antibody negative.
This case was vigorously discussed at CROI and went viral in the media. Questions raised have centered on the baby’s viremia and whether this represented “true” infection or a transient passive “flush” of the mother’s HIV, especially given the nature of the delivery. If the latter, some argued, this may be more a case of successful post-exposure prophylaxis than a true cure — still noteworthy, if less dramatic.
HIV prevention again included several discussions of “treatment as prevention” but also pre-exposure prophylaxis (PrEP), in which uninfected but at-risk persons receive ART. The major announcement at CROI was that each arm of the large VOICE trial in African women failed to show protection. Oral tenofovir or the combination of tenofovir and emtricitabine or vaginal tenofovir gel were compared in a prospective study of more than 5,000 patients. Researchers linked failure to low adherence, estimated at below 30%. This linkage has been previously reported in other PrEP trials, underscoring the urgent ongoing need for the inclusion of behavioral research and support, even as the focus of many investigators has shifted to so-called biomedical prevention approaches. In the end, as with many health challenges, it’s as much about the motivation of individuals as it is about the technology being tested. Still, this negative result poses a huge challenge as we imagine the even larger barrier in applying similar preventions in the “real world,” where adherence support is truly minimal or even absent altogether.
A term now entrenched in HIV circles is the “treatment cascade,” and this was an important CROI theme. In essence, individual treatment goals can be extended to an entire population. This interface of personal and public health seeks to increase HIV testing rates, access to and long-term retention in care and full viral suppression in as close to 100% of infected persons as possible. Each stage in this cascade has unique obstacles and opens research opportunities to understand and reduce barriers to optimum outcomes. As similar problems plague other chronic diseases, HIV research will remain in the vanguard in informing our health care system at a particularly vulnerable time.
The field of HIV research has intersected that of HCV investigation for years, and CROI has provided a stage for many important discoveries. At a clinical level, most have addressed the common coinfection of individuals with HIV and HCV. In many clinics, ID/HIV specialists collaborate with hepatology colleagues for HCV treatment in coinfection, but increasingly also in HCV mono-infection. This trend is expected to accelerate, given the scarcity of trained hepatologists, the antiviral treatment experience of the ID/HIV specialists and the approaching availability of all oral HCV treatment regimens.
As Infectious Diseases News has well covered, HCV therapy is in the midst of a true revolution. Beginning with HCV protease inhibitors, but now expanding to other drug classes of oral direct-acting agents (DAA), HCV cures may soon become commonplace. In one small but impressive trial reported at CROI, investigators reported 100% cures after just 12 weeks of oral dual treatment in genotype 1 HCV in those who were treatment-naïve, as well as in those failing previous interferon-based therapy. This trial, ELECTRON, used two Gilead drugs, sofosbuvir and GS-5885, now called ledipsavir, in 25 treatment-naive and nine previous treatment failures. Many other oral agents in several classes are in development from other companies, making this field an exciting one to watch. As these drugs, hopefully, are approved, the expected dramatic expansion of HCV treatment demand will necessarily increase participation by ID/HIV specialists. At the same time, the expected high treatment costs, coming at a time of health care spending constraints, demand thoughtful prospective planning.
No brief summary can do justice to a meeting as rich and varied in new data as CROI. While other HIV conferences play significant roles in research in this field, CROI is uniquely concentrated in presenting new discoveries. As judged by this year’s meeting, the state of our discipline remains strong.