July 31, 2012
2012 has already brought us many changes to our strategies and options regarding the treatment of HIV. Just days ago, the U.S. Food and Drug Administration (FDA) approved tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis (PrEP), the first biomedical intervention to prevent HIV infection. The FDA also approved the first at-home, over-the-counter test for HIV. The year also marks the emergence of two major themes: treatment as prevention (TasP) and the "cascade" of engagement in HIV care.
Here at the AIDS 2012 conference in Washington, D.C., there were several important oral and poster presentations on antiretroviral therapies. Here's a quick synopsis of the highlights.
The HTPN 052 study has already garnered acclaim in proving that antiretroviral treatment prevents HIV transmission. Here, additional data confirmed that early (rather than delayed) treatment for persons with CD4+ cell counts between 350 and 500 resulted in fewer AIDS events and tuberculosis (TB).
The ANRS group (France's National Agency for AIDS Research) presented encouraging data from their REFLATE study on the use of raltegravir (Isentress) for antiretroviral treatment of TB-coinfected patients who were receiving rifampin-containing anti-TB treatment.
Our group, the International Association of Physicians in AIDS Care (IAPAC), hosted a symposium on the first-ever evidence-based guidelines on improving entry into and retention in care, as well as adherence to antiretroviral treatment.
Previously this summer, a U.S. FDA panel recommended approval of the "quad" pill, which is coformulated with tenofovir (Viread), emtricitabine (FTC, Emtriva), the new pharmacokinetic booster cobicistat and the new integrase inhibitor elvitegravir. Investigators provided additional details of the quad's 48-week non-inferiority versus efavirenz (Sustiva, Stocrin) and versus boosted atazanavir (Reyataz), showing high suppression rates of the new combo in persons with very high viral loads (greater than 400,000 copies/ml).
Data from a Phase 3 study (Gilead 114) showed that cobicistat was similar to ritonavir (RTV, Norvir) in boosting atazanavir when either drug was taken alongside tenofovir/emtricitabine by treatment-naive persons.
The newest HIV integrase inhibitor dolutegravir was shown to be non-inferior to raltegravir when used with two NRTIs in a Phase 3 clinical trial among treatment-naive persons. The regimens were very well tolerated and there was little emergence of drug resistance.
In a press release last week, study sponsors also provided information on a companion study called SINGLE, which concluded that the regimen of abacavir/lamivudine (Epzicom, Kivexa) plus dolutegravir was superior to the industry standard regimen efavirenz/tenofovir/emtricitabine (Atripla).
Five-year data on the MERIT-ES study was presented here, showing continued similar effectiveness of maraviroc (Selzentry, Celsentri) versus efavirenz, when either drug was taken with zidovudine/lamivudine (Combivir) by treatment-naive people.
In a study that highlights the continued search for that elusive, successful NRTI-sparing regimen, a small trial exploring maraviroc versus tenofovir/emtricitabine (when either drug was taken with atazanavir/ritonavir) showed lower virologic response rates in the maraviroc arm (68% vs. 82%). A similar, single-arm pilot study looking at maraviroc combined with ritonavir-boosted darunavir (Prezista) showed a lower-than-hoped-for response rate, particularly among people with high viral loads.
The final five-year follow up on the important BENCHMRK studies (raltegravir with optimized background treatments) showed durable virologic suppression, with few treatment failures.
The 240-week analysis of the STARTMRK study also showed that treatment-naive persons who took raltegravir (with tenofovir/emtricitabine) had excellent long-term viral suppression and tolerability with better responses than those who took the efavirenz combination. Are we seeing a bar raising?
Results of the SPIRIT study showed the non-inferiority of switching patients on stable, boosted-protease inhibitor regimens to the fixed-dose combination of rilpivirine/tenofovir/emtricitabine (Complera). The data also showed a lower rate of virologic non-suppression in subjects switching treatment (1% vs. 5%). Not unexpectedly, those who switched had improvements in lipid parameters.