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Tipranavir 500/100 or 200 vs Kaletra in Naives
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Excerpted from: "Boosted PIs and Other First-Line Strategies"
Glasgow Meeting: Part 4
8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006, Glasgow
Mark Mascolini
Four trials presented at the Glasgow meeting offered insights into first-line fosamprenavir/ritonavir, and three of them appraised 100 mg of ritonavir once daily as the boosting dose. Other investigators sized up the merits of first-line boosted tipranavir or saquinavir, fixed-dose abacavir/lamivudine (3TC) plus atazanavir/ritonavir once daily, and an induction-maintenance scheme that fell short.
Up-front tipranavir can't match lopinavir
An international trial pitting first-line tipranavir/ritonavir at two different doses against lopinavir/ritonavir for 60 weeks found the higher tipranavir/ritonavir dose (500/200 mg twice daily) too toxic and the lower dose (500/100 mg twice daily) too weak to merit consideration for treatment-naive people [7]. With so many once-daily PI options available for starting regimens, whether a different twice-daily tipranavir/ritonavir dose would fare better seems a moot question.
David Cooper (National Centre in HIV, Sydney) and confreres in Argentina and Thailand randomized 558 previously untreated people to one of the two tipranavir/ritonavir doses or to standard-dose lopinavir/ritonavir plus 3TC and TDF. Median pretreatment viral load stood just above 100,000 copies and median CD4 count just above 200. While 11% of study participants had fewer than 50 CD4 cells when entering the trial, 16% had hepatitis C infection.
About 85% of participants completed 48 weeks of treatment. At that point the proportion of people who had a viral load below 50 copies without changing antiretrovirals was 69.2% in the lopinavir arm, 66.7% in the tipranavir/ritonavir-200 arm, and 65.8% in the tipranavir/ritonavir-100 arm. Those results suggested the three regimens are equivalent. But 15 people in the three arms reached their first sub-50 load at week 48. Since the trial's primary endpoint mandated a confirmed sub-50 load for the between-arm comparisons, Cooper and colleagues went on to compare 60-week sub-50 results. Statisticians reckoned that after 60 weeks tipranavir/ritonavir-100 did not meet predetermined criteria that would establish it as noninferior to lopinavir/ritonavir. In plain English the 500/100-mg twice-daily dose was virologically inferior to lopinavir/ritonavir in pushing viral loads under 50 copies.
In the same 60-week analysis the 500/200-mg dose of tipranavir/ritonavir did prove virologically noninferior to lopinavir/ritonavir--but at the cost of more toxicity. Rates of investigator-defined drug-related "adverse events" measured 55% for lopinavir/ritonavir, 62.5% for tipranavir/ritonavir-100, and 69% for tipranavir/ritonavir-200. While 3% stopped lopinavir/ritonavir because of side effects, 7% stopped 500/100 mg of tipranavir/ritonavir and 10% stopped 500/200 mg. Significantly fewer people taking the higher tipranavir/ritonavir dose (82%) than taking the lower dose (94%) or taking lopinavir (97%) remained free of grade 3-4 alanine aminotransferase elevations through 48 weeks (P = 0.001).
Cooper and colleagues concluded that "at the doses tested in this trial, tipranavir/ritonavir cannot be recommended for antiretroviral-naive patients infected with wild-type HIV-1."
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