Transcript ptnaids.pl
ŚLĄSKA AKADEMIA MEDYCZNA W KATOWICACH KATEDRA I ODDZIAŁ KLINICZNY CHORÓB ZAKAŹNYCH SZPITAL SPECJALISTYCZNY ODDZIAŁ DIAGNOSTYKI I TERAPII AIDS Zjednoczenia 10, 41-500 Chorzów, e-mail: [email protected] Terapia ARV u chorych z koinfekcją HIV/HBV/HCV – czy istnieją preferencyjne schematy ARV. Marek Beniowski 1. WHO Regional Office for Europe – DRAFT- WHO Clinical Protocol on Hepatitis C and HIV Co-Infection, WHO Clinical Protocol on Hepatitis B and HIV- CoInfection – 22 Dec 2005 Alberti A, Clumeck N, Collins S, Gerlich W, Lundgren J, Palu G, Reiss P, Thiebaut R, Weiland O, Yazdanpanah Y, Zeuzem S. Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol. 2005 May;42(5):615-24. HBV/HIV Therapeutic Management of HBV/HIV Patients Patients not requiring hepatitis B or ARV treatment Patients requiring only hepatitis B treatment Patients requiring only ARV treatment Patients requiring both hepatitis B or ARV treatment Recommendations for initiating HAART in HBV/HIV co-infected patients CD4 Cells Criteria < 200 cells/mm3 200- 350 cells/mm3 Recommendations Antiretroviral treatment is recommended ART regimens should contain 2 dual-activity (HBV and HIV) drugs Antiretroviral treatment should be considered (high viral load or rapid decline in CD4 count) but should be started before it falls to less than 200 cells/mm3 ART regimens containing 2 dual-activity (HBV and HIV) drugs is indicated (if indication of HBV treatment) or highly recommended First line HAART regimens for HBV/HIV co-infected patients ART regimen Combination drugs Preferential 1st line 2 NRTI + 1 NNRTI TDF + (3TC or FTC(1)) + EFV(2) Alternative 1st line Triple nuke regimen ZDV + (3TC or FTC(1)) + TDF Emtricitabine (FTC) is equivalent to 3TC and is available in association with TDF as a fixed dose combination. NVP can be considered instead of EFV in patients without hepatic dysfunction and with close monitoring. It should be avoided in women with CD4 count >250 cells/mm3 or in men with CD4 count >400 cells/mm3 Second line HAART for HBV/HIV co-infected patients NB: ART regimen TDF/3TC should 2 NRTI + busted PI be maintained for hepatitis treatment, in addition to the 2nd line HAART 1 NNRTI + 1 NRTI + busted PI 2 PIs (one busted) Combination Drugs LPV/r or ABC + (ddI or d4T(3)) + SQV/ or NFV LPV/r or EFV + (ABC or d4T(3)) + SQV/r or NFV LPV/r + SQV or LPV/r + EFV d4T can be considered as an option in 2nd line ART if ZDV was not used in 1st line 4.3. HIV-infected patients with clinical evidence of cirrhosis Clinical cirrhosis is an absolute indication for treatment. HBV DNA threshold for initiation of HBV treatment is lower than in patients without cirrhosis (over 200 UI/ml, that is, as soon as detectable). No medications are contra-indicated for patients with compensated cirrhosis. Patients with decompensated cirrhosis should be referred for palliative care. Patients with cirrhosis require clinical observation, liver function monitoring and drug monitoring (if available). It might be necessary to adjust the dose of ARV metabolised by the liver. If this is not feasible, then ddI and d4T have to be avoided and a regimen containing PI should be closely monitored. 4.4. HIV-infected patients with 3TC resistant HBV strains 3TC (LAM): 50% and 90% of co-infected patients, respectively, after 2 and 4 years of 3TC therapy. In the presence of suspected Lamivudineresistance, the first step is to confirm if resistance testing is available. Otherwise resistance may be suspected if HBV viral load increases more than 1 log in a compliant patient taking 3TC; 3TC will have to be switched to TDF. TDF is essential ARV for the HAART regimen in 3TC resistant patients. HCV/HIV Clinical Management of HCV/HIV Patients HCV/HIV co-infection, patients can be split into four categories: patients not requiring hepatitis C or HIV/AIDS treatment patients requiring only hepatitis C treatment patients requiring only HIV/AIDS treatment patients requiring both hepatitis C and HIV/AIDS treatment Therapeutic algorithm for anti HCV treatment in HIV-infected patients 2.1. When to Start HAART in HCV/HIV Co-Infected Patients CD 4 Cells Criteria Recommendations CD4 < 200 cells/mm3 Antiretroviral treatment is recommended CD4 200-350 cells/ mm3 Antiretroviral treatment should be considered (high viral load or rapid decline in CD4 count) but should be started before it falls to less than 200 cells/mm3 First Line HAART Regimens for HCV/HIV Co-Infected Patients Prefere ntial 1st line Alternat ive 1st line 2 NRTI + 1 NNRTI ZDV(2) or d4T EFV(1) 3TC or FTC3 ABC or TDF Triple nuke regimen ZDV(2) NVP(1) ABC(4) 3TC or FTC3 d4T TDF First Line HAART Regimens for HCV/HIV Co-Infected Patients EFV has been considered the preferential NNRTI option, but NVP can be considered in patients without evidence of hepatic dysfunction and with close monitoring. However, NVP should be particularly avoided in HIV+ patients if CD4 is >250 in women or >400 in men. EFV should be used with caution in women of childbearing age (Class D – FDA) and also because of additional risk of depression. Emtricitabine (FTC) is equivalent to 3TC. FTC is available together with TDF, and 3TC is available together with ABC as a FDC, so FDC: FTC + TDF, and 3TC + ABC. ZDV/3TC/ABC regimen is available as FDC. In case of severe toxicity and side effects caused by 1st line ARVs, it is recommended to substitute to another ARV with a different toxicity profile, but within the 1st line regimens. Switching to 2nd line ARV regimens is recommended in the absence of immunological or virological response to ART, measured by CD4 cell count and viral load. Treatment Regimens for second line therapy in HIV/HCV co-infection Regimen Preferential 2nd line Alternative 2nd line 2 NRTI + boosted PI Combination Drugs LPV/r or SQV/r or ATZ/r (6) ABC/TDF + or ABC/ddI(5) 1 NNRTI +/- 1 NRTI ABC TDF + boosted PI SQV/r LPV/r ATZ/r(6) z: EFV Lub: LPV/r + SQV lub LPV/r + EFV (5) ddI dose in combination with TDF should be adjusted to less than 4.1mg/kg per day as not to compromise immune recovery. It is contraindicated in patients with cirrhosis and under RBV treatment. It should be used with caution in patients with less severe liver disease. (6) Unboosted ATZ or NFV can be used. Second Line HAART for HCV/HIV Co-Infected Patients Three different drugs containing at least one new pharmacological class. The best options are regimens which contain a boosted PI as the key drug, associated with 2 nucleosides if a classical approach with 2 NRTI + 1 NNRTI was chosen for first line therapy. In case of a simplified first choice with 3 NRTI, the second line should use a boosted PI + 1 NNRTI +/- 1 NRTI. Among second line NRTIs, those with the better resistant profile, such as ddI, ABC and TDF, should be given preference. Combination of d4T+ddI has to be avoided due to risk of mitochondrial toxicity, leading to hepatic steatosis and potentially enhancing fibrosis. TDF/ddI is also contra-indicated due to pharmacological negative interactions. Algorithm for initiation of hepatitis C treatment and HAART in HCV/HIV coinfected patients Patients Non treated patients HAART No indication for ARV Treat HCV first Indication for ARV initiation CD4 200 – 350 cells/m3 Treat HCV first, then initiate HAART Initiate HAART Wait until stable, and regimen is well tolerated Then treat HCV CD4 <200 cells/mm3 ARV treated patients HCV treatment Continue HAART Replace ddI and ZDV if on alternative options Possibility to interrupt HAART until the end of Hep C treatment (if CD4 nadir was never <300-350 cells/mm3, and patient asks for it) Treat HCV if CD4 >200cells/mm3 Algorithm for Initiation of Treatment for HCV/HIV Co-Infected Patients If chronic hepatitis C is detected early in the course of HIV infection in patients who do not need HAART, hepatitis C treatment is advised before the initiation of HAART. If a co-infected patient has severe immune deficiency (CD4 count <200 cells/mm3), the CD4 cell count should be improved using HAART before commencing anti-HCV treatment. If CD4 is between 200 cells/mm3 and 350 cells/mm3, HCV treatment should be offered first in order to avoid interactions between HAART and anti HCV drugs and facilitate adherence. After HCV treatment is finished (12 months), HAART should be initiated.