Widely considered the most important HIV scientific conference of the year, the 15th annual Conference on Retroviruses and Opportunistic Infections (CROI), held in Boston last week, did not disappoint. What follows are highlights from this year’s conference. For an even more complete list of our CROI coverage—articles and video interviews are still being added—check out our conference page or click on the links below:

HAART and the Heart

We don’t know about the connections between HIV, antiretrovirals (ARVs) and the risk of cardiovascular disease. But we’re learning:

  • Perhaps the most talked about research at CROI was the finding that abacavir—the active agent in Ziagen and a component of Epzicom and Trizivir—almost doubles the risk of a heart attack in HIV-positive people. According to new data from the international Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, using abacavir or didanosine (Videx EC) raises the risk of a heart attack by 90 and 49 percent, respectively. Taking other nucleoside reverse transcriptase inhibitors (NRTIs)—including stavudine (Zerit), a drug known to increase artery-clogging cholesterol levels—did not.

Experts, including D:A:D researchers, stress that these percentages must be interpreted carefully. For abacavir users with few heart disease risk factors—such as nonsmokers with healthy cholesterol levels—a 90 percent jump may have little impact on their low overall heart attack risk. For abacavir users who do have other cardiovascular risk factors, the study authors suggest discussing these results with a health care provider.

  • But which is the greater risk to our hearts—antiretroviral treatment or HIV itself? Studies at CROI found that, compared with those on stable ARV therapy, people with untreated HIV infection are more likely to have elevated blood markers of cardiovascular inflammation and artery blockage, including IL-6, D-dimer, C-reactive protein and others. In video interviews (Part I and Part II) with AIDSmeds.com associate editor David Evans, Donald Kotler, MD, of St. Luke’s-Roosevelt Hospital in New York, reviews these data and discusses the latest regarding HIV and heart health.

On the Horizon

Unlike past CROIs, there wasn’t a torrent of presentations detailing experimental ARVs in the drug development pipeline. But there were some eye-catching reports:

  • Schering-Plough’s vicriviroc showed well in a Phase II study involving patients with limited ARV options due to drug resistance. The VICTOR-E1 clinical trial evaluating the safety and effectiveness of the CCR5-blocking entry inhibitor suggests that a once-daily 30 mg dose of the drug, combined with a boosting dose of Norvir, is the best bet for testing in Phase III studies of the drug.
  • Treatment pickings can be slim for HIV-positive children. This is a big problem for pediatric patients with drug-resistant HIV and in desperate need of ARV options. The U.S. Food and Drug Administration will soon review the results of a Tibotec-sponsored study showing that the protease inhibitor Prezista (darunavir), boosted with low-dose Norvir, is safe and effective using weight-based dosing for treatment-experienced children between 6 and 17 years of age.
  • Gene therapy continues its exciting development course. Virxsys, a Maryland-based biotech company, is experimenting with a hollowed-out version of HIV—a vector—that can deliver HIV-busting genetic material to CD4s. The genetic payload essentially reprograms infected cells to produce faulty versions of the virus. Data presented at CROI involving nine patients who underwent single-dose therapy with VRX496 indicate profound and sustained antiviral activity. A larger clinical trial of the treatment involving 54 HIV-positive people is currently underway.
  • Also on the high-tech horizon is the brewing partnership between two modern sciences: drug discovery and nanotechnology. As was evident in a handful of CROI presentations, nanoparticles—microscopic polymers—are being used to develop long-acting antiretrovirals (ARVs) that may need to be administered once every few weeks or months. Researchers at Tibotec showed encouraging nanotech data involving its experimental non-nuke rilpivirine (TMC278), and University of Omaha researchers have been toying with long-acting versions of lopinavir and ritonavir (Kaletra) and efavirenz (Sustiva).

Defining Current Treatment Options

We rely on the latest results from studies of experimental ARVs. But we also depend heavily on data from clinical trials further exploring the safety and effectiveness of HIV drugs we already have with us.

  • Pfizer’s Selzentry (maraviroc), Merck’s Isentress (raltegravir) and Tibotec’s Intelence (etravirine) were all approved over the past year, with little more than 24 weeks of safety and efficacy data to prove their worth. At CROI, 48-week results from Phase III studies of the drugs confirmed that these drugs can go the distance for treatment-experienced patients.
  • Results from the international CASTLE study show that Norvir-boosted Reyataz (atazanavir) is comparable to Kaletra in first-time treatment takers. The study findings, which also noted fewer lipid and gastrointestinal problems among Reyataz/Norvir recipients, lend further support to the listing of this once-daily drug pairing as a “preferred” protease inhibitor option in U.S. treatment guidelines.
  • The treatment guidelines also list Epzicom (abacavir and lamivudine) and Truvada (tenofovir and emtricitabine) as the preferred nucleoside reverse transcriptase inhibitor (NRTI) options for HIV-positive people beginning ARV treatment for the first time. Both have long been popular for their once-daily, two-drugs-in-one characteristics—but haven’t been compared head to head until now. When combined with Kaletra in the GlaxoSmithKline-sponsored HEAT study, the drugs were found to be comparable and well-tolerated for up to 48 weeks of treatment.
  • There have been questions about the use of once-daily Kaletra in first-time ARV users, notably those with high pretreatment viral loads. Abbott hopes to address lingering concerns with the successful completion of a large clinical trial, confirming that once- and twice-daily tablet doses of the popular protease inhibitor have similar tolerability and comparable efficacy.
  • The effectiveness of once- vs. twice-daily Viramune (nevirapine) was the question put to a team of European researchers. An analysis of two cohort studies suggest that once-daily Viramune is at least as effective as twice-daily dosing. Boehringer Ingelheim also announced that an extended-release version of Viramune is being studied for once-a-day use.

Don’t miss our two interviews with David Hardy, MD, of the University of California, Los Angeles (UCLA), discussing the latest research efforts to refine HIV treatment options for treatment-naive and treatment-experienced patients.  There’s also POZ magazine Editor-in-Chief Regan Hofmann’s videocast with UCLA’s Judith Currier, MD, reviewing the latest research and treatment issues involving women living with HIV.   

Prevention Attention

HIV transmission and prevention research was a main attraction at this year’s CROI. Several reports detailed successes—and setbacks—in the areas of mother-to-child transmission prevention, circumcision, vaccines and other biomedical strategies.

  • Male circumcision may reduce men’s risk of being infected with HIV. But it doesn’t appear to curb the transmission of the virus from men who are already positive to their female partners. These sobering new results from a study conducted in Rakai, Uganda, further indicate that the risk of transmission was likely increased among couples who resumed sexual intercourse before the male partner’s circumcision wound had healed completely.
  • Good bacteria limits the amount of HIV detected in the genital secretions of women infected with the virus, according to researchers in Seattle and Rochester. The presenting authors hope that their findings, suggesting that HIV-positive women with healthy levels of vaginal Lactobacillus may be less likely to transmit the virus, will lead to additional research testing Lactobacillus supplementation—a common ingredient in yogurt—as a prevention strategy.

And be sure to check out these interviews with three leading transmission and prevention experts:

  • Valerie Stone, MD, of Harvard Medical School and Massachusetts General Hospital talks with Regan about HIV prevention and women.
  • A discussion with Susan Buchbinder, MD, of the San Francisco Department of Public Health regarding the latest biomedical prevention research regarding vaccines, microbicides and pre-exposure prophylaxis (PrEP).
  • An exclusive interview with Bernard Hirschl, MD, one of the authors of the controversial Swiss consensus statement concluding that HIV-positive people on an effective ARV regimen and free of sexually transmitted infections (STIs) are unlikely to transmit the virus to their HIV-negative sex partners. 

Keep your eyes focused on POZ.com and AIDSmeds.com for written and video coverage from the XVII International AIDS Conference, taking place Mexico City, Mexico, August 3–8, 2008.