Guidelines for Tipranavir Use

The American Academy for HIV Medicine (AAHIVM.org) issued these guidelines on their website for the use of tipranavir.

Tipranavir (tipranavir), co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of tipranavir of 24 weeks duration. Both studies were conducted in clinically advanced, 3-class antiretroviral treatment-experienced adults with evidence of HIV-1 replication
despite ongoing antiretroviral therapy.

The approved dose of tipranavir (Aptivus®) is 500 mg taken with 200 mg of ritonavir (TPV/r), twice daily. Tipranavir must be co-administered with ritonavir to boost the therapeutic levels of tipranavir; otherwise, levels of tipranavir will be insufficient to inhibit HIV replication. TPV/r must be taken in combination with other anti-HIV medications.

The following points should be considered when initiating therapy with tipranavir/ritonavir:

o The use of other active agents with tipranavir/ritonavir is associated with a greater likelihood of treatment response.

o Genotypic or phenotypic testing and/or treatment history should guide the use of tipranavir/ritonavir. The number of baseline primary protease inhibitor mutations affects the virologic response to tipranavir/ritonavir.

o Liver function testing should be performed at initiation of therapy with tipranavir/ritonavir and monitored frequently throughout the duration of treatment.
Use caution when prescribing tipranavir/ritonavir to patients with elevated transaminases, hepatitis B or C co-infection or other underlying hepatic impairment.

o The extensive drug-drug interaction potential of tipranavir/ritonavir when co-administered with multiple classes of drugs must be considered prior to and during tipranavir/ritonavir use.

o The risk-benefit of tipranavir/ritonavir has not been established in treatment-naļve adult patients or pediatric patients.

o Lipids (triglycerides and cholesterol profiles) should be monitored regularly as hyperlipidemias were reported during the licensing trials.

The results of the RESIST studies showed:

1) Improved treatment response defined as confirmed > 1 log10 drop in HIV VL from baseline at 24 weeks in 40% vs. 18% comparator arms.

2) An ITT analysis of tipranavir vs. comparator demonstrated HIV VL < 400 copies/mL in 34% vs 16% respectively; 23% vs. 9% HIV VL < 50 copies/mL.

3) Median change from baseline in CD4+ cell count at week 24 was +34 cells/mm3 in patients receiving tipranavir/r (n=582) versus +4 cells/mm3 in the comparator group of ritonavir-boosted PIs (n=577).

4) Tipranavir/r was associated with reports of clinical hepatitis and hepatic decompensation including some fatalities. When prescribed, LFTs should be monitored closely and patients informed to contact their provider immediately if they experience any symptoms consistent with hepatic dysfunction.

Suggested Guidelines:

1) Tipranavir/ritonavir should be considered for: A) persons who are highly treatment experienced or B) persons in whom genotypic resistance testing indicates resistance to multiple PIs.

2) Genotypic resistance testing, where available, should guide the decision to use this combination; in RESIST-1 and 2, poorer outcomes occurred in patients with more numerous (5 or more) primary PI mutations at baseline unless used with T-20.

3) Extra vigilance should be used if tipranavir/ritonavir is prescribed to patients with underlying hepatic disease such as chronic active HBV, HCV or non-alcoholic steatosis. If it is used in patients with underlying liver disease, these patients should be monitored very closely for exacerbations of their liver dysfunction.

4) If patients have baseline abnormal LFTs, these should be evaluated first before initiation of tipranavir/ritonavir.

5) In RESIST, some patients with normal baseline transaminases developed significant LFT abnormalities. Close monitoring of LFTs is recommended with use of tipranavir/ritonavir.

* NB: Because tipranavir must be boosted with ritonavir, be certain that the patient has both ritonavir and tipranavir at time of initiation of the new regimen. The Abbott Patient Assistance Program may be utilized to obtain free Norvir (ritonavir) (Website:
http://abbottvirology.com/Pages/Assistance.asp).
* The application must be completed by both the patient and provider.

LINKS

Tipranavir & Effect of Using Active HIV Drugs
(08/30/05)
www.natap.org/2005/ias/ias_43.htm 

Tipranavir: long-term safety/tolerability (08/30/05)
www.natap.org/2005/ias/ias_42.htm
 
Tipranavir: predicting viral response"Non-response to Tipranavir is Associated with Pretreatment Resistance Characterized by Tipranavir Phenotype or Genotypic Tipranavir Score" ...
www.natap.org/2005/resistance/drw_4.htm


Tipranavir/Ritonavir Outdoes Other Boosted PIs in Phase 3 Trial
Tipranavir/Ritonavir Outdoes Other Boosted PIs in Phase 3 Trial ... The fold-change resistance to tipranavir averaged only 1.9-fold. ...
www.natap.org/2004/ICAAC/icaac_01.htm


Choosing When to Use Tipranavir
Choosing When to Use Tipranavir ... 104) presented resistance data from the pivotal tipranavir RESIST trials for Boehringer Ingelheim. ...
www.natap.org/2005/CROI/croi_38.htm


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