New treatment option for HIV, TB coinfection
The integrase inhibitor raltegravir (Isentress) may be a good substitute for efavirenz (Sustiva) in HIV patients starting treatment for HIV and tuberculosis (TB) at the same time, a researcher said here.
In a phase II randomized open-label study, the drug – tested at two doses -- had success rates similar to efavirenz, according to Nathalie de Castro, MD, of the University of Paris Diderot in Paris.
But a higher dose of 800 mg twice a day appeared to yield slightly better results, although the optimal dose has yet to be determined, de Castro told a late-breaker session at the International AIDS Conference.
Regimens based on efavirenz are recommended for first-line treatment of coinfected patients, but some side effects – rash, central nervous system toxicity, and teratogenicity, among others – may limit its use, de Castro said.
Raltegravir has a good safety profile, she noted, but, on the other hand, TB treatment with rifampin (Rifadin, Rimactane) can lower the effective levels of the drug because of rifampin's ability to induce metabolism of raltegravir.
To explore the issue, she and colleagues in France and Brazil analyzed outcomes for 153 HIV treatment-naive patients randomly assigned to 600 mg daily of efavirenz, or twice-daily raltegravir at either 400 or 800 mg.
Patients were concomitantly treated for their TB with rifampin-containing regimens.
The primary endpoint of the study was undetectable HIV at week 24, defined as a plasma viral load of fewer than 50 copies of HIV RNA per ml.
Success rates were comparable among the arms, De Castro said:
- 63% of those in the efavirenz arm had undetectable HIV.
- 76% of those getting the 400-mg dose of raltegravir met the primary endpoint.
- And 78% of those getting 800 mg twice daily of raltegravir had undetectable virus.
- The 95% confidence intervals of all three of those proportions overlapped.
De Castro noted that, while the 24-week proportions were similar, patients treated with raltegravir had a faster decline in HIV than those treated with efavirenz.
On the other hand, median counts of CD4-positive T cells rose rapidly and in a similar fashion in all three arms, with an average increment at 24 weeks of between 152 and 180 cells per microliter of blood.
Adverse events were similar in all three arms, she said, adding deaths were rare and were attributed to the TB.
The study shows that it's "safe to explore larger studies using raltegravir in patients coinfected with HIV and TB," commented Joseph Eron, MD, of the University of North Carolina Chapel Hill.
"You don't want to start a 300- or 400-patient study unless you know that (the results) will be in the ballpark," he told MedPage Today, "and they showed it's in the ballpark."
But he cautioned that numbers are small, so that it's difficult to say at this point which dose of raltegravir is best.
The study was supported by university and governmental organizations in Brazil and France; drugs were donated by Merck Sharpe & Dohme-Chibret and Gilead. De Castro did not report any conflicts.
Eron has reported financial links with Merck, GlaxoSmithKline, ViiV, BMS, Tibotec, and Gilead.
Primary source: International AIDS
Conference
Source reference:
Grinsztejn B, et al "A randomized multicentre open-label trial
to estimate the efficacy and safety of two doses of raltegravir
(RAL) to efavirenz (EFV) for the treatment of HIV-TB co-infected
patients: results of the ANRS 12 180 Reflate TB trial"
<em>IAC</em> 2102; Abstract THLBB01.
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