Among the usual conference suspects were drugs, drugs, and drugs! Here are some of the findings on how HIV drugs compare to one another:
In an advanced Phase 3 study, elvitegravir was found to be non-inferior to Isentress. Isentress (generic name raltegravir) has been known for its combination of power and tolerability and is one of four drugs recommended by U.S. treatment guidelines for people taking HIV therapy for the first time, as well as being FDA approved for treatment-experienced people. Isentress, from Merck & Co., is currently the only HIV integrase inhibitor.
Gilead Sciences is developing elvitegravir, an HIV integrase inhibitor that is taken once a day, unlike twice-daily Isentress. The caveat is that it must be boosted with a small dose of another drug, either Norvir or the company's experimental booster cobicistat.
At 48 weeks, 59% of the 351 participants given elvitegravir vs. 58% of the 351 individuals given Isentress achieved undetectable viral loads of less than 50 copies/mL. T-cell count increases were also similar (138 for elvitegravir and 147 for Isentress). Side effects included diarrhea, nausea, and bronchitis, and did not differ between the two drugs.
These study participants were highly treatment-experienced, and the majority had HIV with drug resistance to at least two classes of antiviral medication. This group experiences less treatment success than people starting anti-HIV therapy for the first time. All the participants also received a fully active boosted protease inhibitor drug (meaning that their virus was not resistant to it). Still, one in five participants in both groups experienced virologic failure (detectable viral load). Only a minority of those, however, had drug resistance to the integrase inhibitor drug class (approximately 20%).
The study is continuing out to 96 weeks. Elvitegravir is also being studied in two other Phase 3 studies in treatment-naive people (taking therapy for the first time), as part of a complete regimen-in-one-pill known as the Quad. The four medications in the Quad are Truvada (made up of Viread and Emtriva) and elvitegravir boosted with cobicistat.
Edurant (generic name rilpivirine) was approved by the FDA in May. At IAS, Janssen Therapeutics presented 96-week data from two of its Phase 3 studies with Edurant (ECHO and THRIVE). Edurant and Sustiva (both from the drug class non-nucleoside reverse transcriptase inhibitors, NNRTIs or non-nukes) had similar viral load decreases out to 96 weeks: 78% of participants taking either drug had undetectable viral loads. People taking Edurant, however, had twice the virologic failure rate of those taking Sustiva, 14% vs. 8%. They also had a higher rate of never having achieved undetectable viral load to begin with, 7% of the Edurant group vs. 3% of the Sustiva group. On the other hand, participants given Sustiva had a higher rate of side effects, including discontinuation due to a drug-related adverse event (9% of the Sustiva group vs. 4% of the Edurant group).
Merck & Co. reported on nearly five years of data with Isentress. At 240 weeks, 69% of the 160 study participants taking an Isentress regimen had an undetectable viral load, compared to 63% of the 38 individuals taking a Sustiva regimen. T-cell increases were also similar, 302 cells for the Isentress group and 276 for the Sustiva group. Drug-related adverse events were higher in the Sustiva group -- 76% vs. 55% for those taking Isentress. All participants were taking HIV therapy for the first time.
An HIV drug therapy backbone usually consists of nucleoside medications, the oldest HIV drug class. Although the nukes have come a long way, there's interest in moving on to regimens that don't depend on them. Two studies looked at whether the CCR5 inhibitor Selzentry (maraviroc) could replace the popular nuke backbone of Truvada. Of note, Selzentry was given only once daily, at a dose of 150, rather than its FDA approved dose of 150 mg twice daily. That's because the studies combined it with a boosted protease inhibitor (PI) medication (one taken with a small dose of Norvir). Most boosted PIs allow once-daily Selzentry to reach the plasma concentration that it shows with twice-daily dosing.
Italian researchers conducted a small proof-of-concept study comparing an established combination of Kaletra/Truvada against a novel regimen consisting of Kaletra with Selzentry in treatment-naive patients. They reported more effective immune and virologic response with Selzentry. The Selzentry group had a greater increase in T-cell count (226 vs. 125 for the Truvada group). The Selzentry group also had a faster time to undetectable viral load (at 24 weeks) in 79% of participants vs. 14% of those in the Truvada group. However, of the 37 patients who reached 48 weeks, there was no statistically significant difference in undetectable viral load, which was achieved by 94.7% of the 19 persons taking Kaletra/Selzentry vs. 83% of the 18 individuals given Kaletra/Truvada. More research is needed to confirm the study's results.
In an early Phase 2b study, Pfizer compared Selzentry in combination with boosted Reyataz (generic name atazanavir and a small dose of Norvir) to boosted Reyataz/Truvada. Again, Selzentry was taken once daily. At 48 weeks, 75% of the Selzentry group vs. 84% of the Truvada group had undetectable viral loads. These are from small numbers of participants, 59 in the Selzentry group and 61 in the Truvada group. The study will go into Phase 3 later this year, enrolling more participants.
Pfizer also reported pooled results from its MOTIVATE studies looking at Selzentry with boosted PIs. The retrospective analysis found that, as expected, the efficacy of a once-daily Selzentry dose of 150 mg was similar to that of 150 mg taken twice daily. At 48 weeks, 46% of the once-daily group vs. 48% of the twice-daily group had undetectable viral loads. Selzentry, however, cannot be taken once daily with Aptivus and if taken once daily with Lexiva, must be a 300 mg dose. The study reported that once-daily Selzentry worked for these treatment-experienced participants even when they had high viral load or low T-cell counts at the beginning of the study.