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CROI 2014: Progress continues in the fight against HIV/AIDS
Even after 23 years, the Conference on Retroviruses and Opportunistic Infections, or CROI, remains the most vital scientific conference in the international effort against HIV/AIDS. CROI provides witness to many true breakthroughs, and its agenda reflects the shifting currents and new directions of progress.
This year’s CROI held in Boston in early March was no exception. Plenary presentations summarized topics ranging from basic sciences to clinical care to global policy, including new findings and state-of-the-art reviews. Abstract sessions, in a real sense the heart of CROI, showcased cutting-edge new science, often presented by the new generations of investigators keeping HIV science alive and vigorous.
HIV remained front and center
As always, the sheer amount of new material is impossible to summarize in so small a space, but themes can clearly be seen. In the basic sciences, efforts to understand the immunology and virology of HIV pathogenesis continue and have a new focus in the search for a cure. CROI 2014 may be most remembered here by hopeful progress and challenging setbacks. New means of quantifying the nature and amount of HIV persistence in long-lived reservoirs suggest many more latently infected cells than previously estimated. Although this implies cures may be even harder to achieve than expected, CROI also saw another possible “baby cure” in the so-called “Long Beach baby.” Similar to the “Mississippi baby,” this child received antiviral therapy immediately after birth. No detectable HIV has been found, although caution was loudly expressed as the infant continues to receive antiretroviral therapy.
Caution was appropriate, as this year’s CROI attendees also heard that the two Boston lymphoma cases, where HIV was not found after bone marrow transplants, both had viral breakthroughs, damping early optimism.
Paul A. Volberding
Also causing a buzz at CROI were the results of HIV gene therapy reported in The New England Journal of Medicine during the conference. In this work, CD4 cells engineered to carry defective CCR5 genes, one of the main HIV cell surface receptors, survived in human volunteers after reinfusion and declined more slowly than unmodified cells during planned antiretroviral discontinuation. Still, with fits and starts, HIV cure research was very much front and center at CROI and will definitely be worth watching, given the magnitude of research investment cure is receiving.
HIV prevention and treatment also were very much part of CROI 2014. Prevention research based on antiretroviral drugs included discussions of very long half-life injectable agents, perhaps allowing administration as infrequently as every 3 months in the case of a non-nucleoside reverse transcriptase inhibitor from Glaxo SmithKline. This could be particularly significant in the pre-exposure prophylaxis (PrEP) context, where adherence to daily oral medication has proved to be such a substantial barrier. Progress also was reported in topical administration of antiretroviral drugs in the vagina, where a cervical ring impregnated with two drugs demonstrated sustained tissue delivery of one of the agents, with concentrations shown in vivo to protect cervical cells from infection.
New drugs on the horizon
HIV treatment advances at CROI also were significant. One new class of drugs was presented, a novel HIV attachment inhibitor from Bristol-Myers Squibb, showing HIV inhibition in an early clinical trial. The need for new drugs was again underscored at CROI by an elegant report of transmitted drug resistance. Using ever more sensitive techniques, it remains clear that HIV drug resistance is still a cause for concern and that broad resistance will still dictate the need for new drug classes at least in some cases.
Another CROI highlight in 2014 was new antiretroviral treatment strategies. In one interesting report from an ACTG trial, the use of two ritonavir-boosted protease inhibitors, atazanavir (Reyataz, Bristol-Myers Squibb) or darunavir (Prezista, Janssen Products), were compared with the integrase inhibitor raltegravir (Isentress, Merck) — all with a backbone of tenofovir (Viread, Gilead) and emtricitabine (Emtriva, Gilead). All three arms achieved excellent viral suppression, but raltegravir was statistically better than darunavir, whereas atazanavir was discontinued more often than either of the other agents, primarily due to hyperbilirubinemia, jaundice and gastrointestinal side effects.
In another interesting presentation, the use of regimens not including a nucleoside reverse-transcriptase inhibitor backbone resulted in somewhat higher rates of virologic failure and drug resistance, particularly to the integrase inhibitor raltegravir.
Effect of comorbid conditions
Finally, comorbidities of HIV were actively discussed. One very helpful plenary presentation thoroughly reviewed the central nervous system (CNS) consequences of HIV infection in the setting of current ART, and the ongoing controversy of mild cognitive impairment and the utility of selecting drugs thought to be better at CNS penetration. The jury still seems out, but research tools are improving and more progress can be expected. CROI also included yet more evidence that ongoing HIV-associated inflammation is responsible for end-organ damage, most clearly linked to cardiovascular endpoints, including stroke, as well as myocardial infarcts.
CROI 2015 will return to Seattle, once more with the excellent management of its new partner, IAS-USA. We can hope to see substantial cure progress, at least in giving better ability to follow the reservoir size as anti-inflammatory and other drugs enter clinical intervention trials. Within the year, additional one-pill regimens will be approved, and we can expect more data on the community-wide prevention effects of wider HIV screening and earlier treatment. Time in this summary did not allow the inclusion of the truly amazing progress in treating hepatitis C virus infection (cure rates approaching 100% with as little as 6 weeks of treatment), but this work also can easily be predicted to have made great progress. We look forward to our Seattle report at this time in 2015.
Paul A. Volberding, MD, is the Chief Medical Editor of Infectious Disease News. He can be reached at: University of California San Francisco, 50 Beale St., Suite 1300, San Francisco, CA 94105; email: paul.volberding@ucsf.edu.
Disclosure: Volberding reports no relevant financial disclosure.