CROI Round-up

New information on the heart, plus a possible alternative to Norvir and more

HIV a heart risk all by itself

At HIV medical conferences, the same doctors usually get to present on their pet specialties. For HIV and heart disease, Carl Grunfeld, M.D., Ph.D., of the University of California, San Francisco, often reports on the latest information. What did the Grun have to say this year?

“It’s clear—HIV is an additional risk factor,” Grunfeld said. “It is virtually the same” as being male, a smoker, or a diabetic, he reported. “What’s clear from our study is that HIV itself is bad on your atherosclerosis.”—Enid Vázquez

Heart disease with Ziagen and other meds

A previous report from the D:A:D cohort study (Data Collection on Adverse Events of Anti-HIV Drugs) found an increased risk of heart attack in people taking Ziagen or Videx. In an updated report, there was also a higher risk of heart attack in people taking Crixivan or Kaletra. As usual, the risk was higher in those people who already had risk factors, such as smoking, high cholesterol, or older age. The report noted that, “As with any observational study, our findings must be interpreted with caution given the potential for confounding [unknown factors influencing the findings].” Although the relative risk was higher, the actual number of heart attacks in this large cohort (approximately 33,000 individuals) was very low.—EV

Bye, bye, Norvir?

Norvir started out as an HIV drug, one of the “savior” protease inhibitors (PIs) to come out in the mid-1990s. It was hard to stomach, however, and was saved only when it was found useful, in small doses, for boosting the blood levels of other PI drugs, cutting the doses of those meds (and their side effects) while maintaining or improving their power.

That’s nice, but Norvir became a villain when manufacturer Abbott Laboratories raised its price 400%, which compensated for its smaller dosage and took advantage of its wide-spread use. That’s why advocates for HIV treatment, including doctors, have been waiting for years to kick Norvir to the curb. Now that end appears to be in sight.

Not just one but two drugs in development are expected to boost the blood levels of HIV protease inhibitors.

GS-9350 matched Norvir’s boosting of the drug midazolam, meeting proof-of-concept criteria for continued research. In test tube studies, GS-9350 has less of an effect on triglycerides, cholesterol, and insulin resistance (related to diabetes) than does Norvir. GS-9350 also has co-formulation potential, so that it can be given in a pill with the medications it boosts, not just taken separately. Having met these criteria, it went into research as a quad tablet—four medications in one. The three other meds are Viread and Emtriva (which are also available together, known as Truvada) and the experimental elvitegravir, which is an HIV integrase inhibitor drug. With a successful Phase 1 (safety study) behind it, the quad tablet now moves into Phase 2 study, being tested against Atripla, a triple drug in one (Sustiva, Viread, and Emtriva). GS-9350 will also be tested as a booster of the protease inhibitor Reyataz.

GS-9350 is from Gilead Sciences, considered a small company, but one with the blockbuster HIV drugs Viread and Truvada, as well as Emtriva, and which received high praise for working with another pharmaceutical company (Bristol-Myers Squibb) to create Atripla.

The other potential PI booster still in research is SPI-452. In test tube studies, it boosted three protease inhibitors. In an early study, it also caused no increase in triglycerides or LDL (the “bad” cholesterol) compared to a placebo (sugar pill), and has potential for co-formulation. SPI-452 is being developed by Sequoia Pharmaceuticals.—EV

IL-2 fails to demonstrate clinical benefit in two large trials

Results from two large, randomized trials of IL-2 (interleukin-2), in which significant increases in CD4 T-cells were seen in those taking IL-2 injections in combination with antiretroviral therapy (ART), unfortunately did not translate into any clinical benefit, and showed no difference in rates of AIDS diagnoses or death for the IL-2 group versus those on ART alone.

Data from the two studies, ESPRIT and SILCAAT, were presented. Together, the two studies monitored around 6,000 individuals over a 7-year period. In one study, those taking IL-2 were found to be at greater risk for life-threatening adverse events (AEs), including DVT (deep vein thrombosis). While it is not yet clear exactly why the CD4 increases did not confer any benefit, some possible explanations offered were that the adverse events offset any benefit, or that the kind of T-cell being affected by IL-2 differs in function from the type of CD4 which is normally boosted when taking ART. The costly studies, while disappointing, may eventually, following further planned analyses, lead to deeper understanding of the immune system.—Jeff Berry

Indevus’ PRO 2000 becomes first microbicide to demonstrate efficacy

Research on an experimental microbicide known as PRO 2000 has demonstrated that the vaginal gel provides a small amount of protection against HIV in women, according to a study that was presented at CROI.

PRO 2000, manufactured by Indevus Pharmaceuticals, works by binding up HIV and preventing it from attaching to certain white blood cells. This preliminary study, designed to test the safety of the gel, found it to be 30% effective at preventing the onset of infection. These findings miss the mark of statistical significance by three percentage points; however, the study itself is the first to demonstrate the potential for microbicides to be effective.

Conducted by the Center for AIDS Program of Research in South Africa, and funded by the U.S. National Institutes of Health (NIH), the study divided 3,000 women from the U.S. and four different regions in Africa into four groups. One group used the PRO 2000 gel, another used a different microbicide gel produced by Reprotect known as BufferGel, a third group used a placebo gel, and the remaining group used no gel at all. Comprehensive sex education was also provided to the women, and condom use was encouraged.

At the end of the study, 194 women had contracted HIV, 36 of whom were from the PRO 2000 group, 54 from the BufferGel group, 51 from the placebo group, and 53 from the group that used no microbicides.—Keith R. Green

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