Though this year’s Conference on Retroviruses and Opportunistic Infections (CROI) won’t likely be remembered for HIV prevention or treatment breakthroughs—there weren’t any—it certainly confirmed that research into the virus and its complications continues at a dizzying clip.
From February 16 to 19, more than 4,000 delegates from all over the world filled the halls of Moscone Center West in San Francisco to learn from, question and sometimes debate nearly 1,000 scientific presentations, all fascinating in their own way.
What follows are some of the more significant, immediately relevant, research findings shared at the 17th CROI. For an even more complete list of our coverage—video interviews are still being added—check out our conference page or the official retrovirus conference site.
Expanding Treatment Options
Though ARV research was not the focal point of this year’s CROI gathering, we gained some additional—and encouraging—insight regarding a handful of approved treatment options and a good glimpse at a few agents making their way through the development pipeline.
Older Meds, New Data
- Once-daily Norvir (ritonavir)–boosted Prezista (darunavir) may only need to be taken once a day by some treatment-experienced patients, for whom twice-daily dosing remains the only approved option. Though the ODIN study showed comparable viral load decreases and CD4 gains in those receiving once-daily versus twice-daily dosing, the study excluded patients with any degree of HIV resistance to Prezista. Thus, it’s unclear how well once-daily Prezista-based regimens will work for the resistance challenged.
- Among HIV-positive patients with viral loads below 100,000 copies per milliliter (mL), there’s no difference in long-term effectiveness between those using Norvir (ritonavir)–boosted Reyataz (atazanavir) or Sustiva (efavirenz) in combination with either Epzicom (abacavir plus lamivudine) or Truvada (tenofovir plus emtricitabine), according to final results from a federally funded study (ACTG 5202). These data are encouraging in light of early results from the same study indicating that people starting treatment with high viral loads experienced virologic failure more rapidly when using Epzicom instead of Truvada.
In the Pipeline
- Gilead Sciences’ experimental “Quad” tablet and boosting agent cobicistat continue to show promise in two ongoing clinical trials reported at CROI. The first study suggests Gilead’s four-in-one pill—containing the experimental integrase inhibitor elvitegravir, cobicistat, tenofovir and emtricitabine—performs as well as the fixed-dose combination tablet Atripla. The second study indicates that cobicistat is comparable with the mainstay booster Norvir (ritonavir) in terms of efficacy and safety.
- Conference delegates also got their first good look at a novel CCR5 receptor antagonist being developed by Tobira Therapeutics. The drug, TBR-652, was found to be effective and well tolerated in a small 10-day study. Thought it works the same as the approved CCR5 blocker Selzentry (maraviroc), Tobira’s contender also holds promise against CCR2, a white blood cell receptor that has been tied to several inflammatory diseases, including atherosclerosis, metabolic syndrome and insulin resistance.
- More sobering results from an advanced clinical trial involving Merck’s CCR5 antagonist vicriviroc were presented, providing an explanation for the company’s decision to not seek approval for the drug, at least for treatment-experienced patients. Compared with those using a placebo plus an optimized background regimen (OBR) of approved agents, vicriviroc plus an OBR did no better in terms of keeping viral loads undetectable. The company is, however, following through on a study involving first-time treatment takers.
Treatment Works
- Men living with HIV maintaining CD4 counts above 500 cells for at least three years while on ARV therapy can anticipate a lifespan similar to that seen among their HIV-negative peers, according to a large European mega-cohort study. More sobering findings were documented among HIV-positive women: Mortality rates, even among those responding well to ARV therapy, were still lower compared with HIV-negative women.
HIV/AIDS Complications
While ARV therapy has greatly improved the length and quality of life for HIV-positive people, side effects and a high risk of non-AIDS-related complications remain all too real. As researchers learn more about these health challenges, they also stumble upon useful clues to prevent and manage them.
Bone Health
- The risk of serious bone fractures—notably of the hip, spine and wrist—is higher among people living with HIV compared with HIV-negative people of similar ages, according to new data from the U.S. Centers for Disease Control and Prevention. Though there has been no shortage of data indicating that people living with HIV are more likely to have decreased bone mineral density (BMD)—osteopenia and, when more serious, osteoporosis—the CDC results are among the first to confirm an elevated risk of fractures in HIV-positive people.
A second study reported at CROI, from the Veterans Administration (VA), suggested that HIV-positive men are more likely to experience bone fractures compared with age-matched HIV-negative men.
- Though the exact causes of BMD decreases in people living with HIV aren’t entirely understood, certain ARVs have been fingered as possible culprits, with some meds being more likely to contribute than others. In an analysis of ACTG 5202 reported at CROI, for example, Truvada was more likely to lead to bone loss than Epzicom, and similarly, Norvir-boosted Reyataz was more likely to contribute to bone loss than Sustiva.
- High rates of vitamin D insufficiency—which contribute not only to bone loss, but also to a long list of other diseases becoming increasingly common among people living with HIV—were reported at CROI. In a CDC study, about 72 percent of 672 HIV-positive study subjects had insufficient levels of 25-hydroxyvitamin D (between 20 and 30 ng/dL). The authors noted, however, that rate of vitamin D insufficiency is about 77 percent in the general U.S. population, suggesting that it’s not necessarily more common among people living with HIV.
Kidney Toxicity
- Continued use of two commonly used ARVs—tenofovir (found in Viread, Truvada and Atripla) and Reyataz, along with the older protease inhibitor Crixivan (indinavir)—is associated with an increased risk of kidney function deterioration, according to an analysis of the large ongoing EuroSIDA study. Tenofovir, for example, was associated with a 16 percent increased risk of chronic kidney disease per year of exposure to the drug, after adjusting the data for other risk factors for kidney disease, such as high blood pressure and diabetes. Fortunately, the absolute risk of chronic kidney disease remains low among people living with HIV.
Cardiovascular Disease
- Though not exactly surprising results, new data from the large Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study confirm that the risk of developing various forms of cardiovascular disease in people living with HIV drops with time upon stopping cigarette smoking. Current smokers, for example, were almost four times as likely to experience a heart attack compared with those who have never smoked. Among those who quit smoking while participating in D:A:D, the risk of a heart attack decreased by about a third after one to two years and by half after three years.
Cancer Answers
- Some good news regarding cancers: If antiretroviral therapy is able to maintain higher CD4 cell counts, it may reduce the risk of various non-AIDS-related cancers in people living with HIV. The healthier the immune system while on ARV therapy, researchers at Kaiser Permanente report, the lower the risk of infection-related cancers (such as HPV-associated anal cancer) and environmental-related cancers (such as lung cancer).
- Speaking of lung cancer, yet another study suggests that HIV infection is an independent risk factor for life-threatening lung tumors—but not nearly to the extent associated with smoking. According to VA researchers, HIV itself appears to be associated with an 80 percent increase in the relative risk of lung cancer. However, it remains a rare ailment among HIV-positive individuals who have never smoked. Current smokers and people who had quit within the past year were almost 10 times as likely to develop lung cancer as people who’d never smoked.
H1N1 Meets HIV
- People with HIV are generally no more likely to experience severe complications of H1N1 influenza virus—swine flu—than people not infected with HIV, according to several studies reported at CROI. However, studies presented in San Francisco also painted a conflicting picture regarding the ability of H1N1 vaccines to spark sufficient immune responses against the virus in people with HIV hoping to avoid the novel influenza virus still circulating the globe.
Access to Care
All the advances in treatment research won’t make a difference for people who don’t know they’re HIV positive and haven’t yet accessed care. Fortunately, a handful of studies reported at CROI suggest that nationwide efforts to increase access to testing and linkage to care are beginning to pay off.
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