Are Specific Antiretrovirals associated with an Increased Risk of Discontinuation due to Toxicities or Patient/Physician Choice in patients with Hepatitis C Virus Coinfection?
Authors: Mocroft Amanda , Rockstroh Jurgen , Soriano Vincent , Ledergerber Bruno , Kirk Ole , Vinogradova Elena , Reiss Peter , Katlama Christine , Phillips Andrew N , Lundgren Jens D ,   EuroSIDA Study Group, Losso M , Duran A , Vetter N , Karpov I , Vassilenko A , Clumeck N , De Wit S , Poll B , Machala L , Rozsypal H , Sedlacek D , Nielsen J , Lundgren J , Benfield T , Kirk O , Gerstoft J , Katzenstein T , Hansen A-B E , Skinhøj P , Pedersen C , Zilmer K , Katlama C , Viard J-P , Girard P-M , Marc T Saint , Vanhems P , Pradier C , Dabis F , Dietrich M , Manegold C , Van Lunzen J , Stellbrink H-J , Staszewski S , Bickel M , Goebel F-D , Fätkenheuer G. , Rockstroh J , Schmidt R , Kosmidis J , Gargalianos P , Sambatakou H , Perdios J , Panos G , Banhegyi D , Mulcahy F , Yust I , Turner D , Burke M , Pollack S , Hassoun G , Sthoeger Z , Maayan S , Vella S , Chiesi A , Arici C , Pristerá R , Mazzotta F , Gabbuti A , Esposito R , Bedini A , Chirianni A , Montesarchio E , Vullo V , Santopadre P , Narciso P , Antinori A , Franci P , Zaccarelli M , Lazzarin A , Finazzi R , Monforte A D'Arminio , Viksna L , Chaplinskas S , Hemmer R , Staub T , Reiss P , Bruun J , Maeland A , Ormaasen V , Knysz B , Gasiorowski J , Horban A , Prokopowicz D , Wiercinska-Drapalo A , Boron-Kaczmarska A , Pynka M , Beniowski M , Mularska E , Trocha H , Antunes F , Valadas E , Mansinho K , Matez F , Duiculescu D , Streinu-Cercel A , Vinogradova E , Rakhmanova A , Jevtovic D , Mokrás M , Staneková D , González-Lahoz J , Sánchez-Conde M , García-Benayas T , Martin-Carbonero L , Soriano V , Clotet B , Jou A , Conejero J , Tural C , Gatell JM , Miró JM , Blaxhult A , Karlsson A , Pehrson P , Ledergerber B , Weber R , Francioli P , Telenti A , Hirschel B , Soravia-Dunand V , Furrer H , Chentsova N , Barton S , Johnson AM , Mercey D , Phillips A , Johnson MA , Mocroft A , Murphy M , Weber J , Scullard G , Fisher M , Brettle R , Loveday C , Clotet B , Antunes Francisco , Blaxhult Anders , Clumeck Nathan , Gatell Jose , Horban Andrzej , Johnson Anne , Katlama Christine , Ledergerber Bruno , Loveday Clive , Phillips Andrew , Reiss Peter , Vella Stefano , Lundgren J , Gjørup I , Kirk O , Friis-Moeller N , Mocroft A , Cozzi-Lepri A , Bannister W , Mollerup D , Podlevkareva D , Olsen C Holkmann , Kjær J 
Published: April 2022

Background

Liver damage associated with hepatitis C (HCV) may influence the likelihood of experiencing discontinuation due to toxicities or patient/physician choice (TOXPC) in patients taking combination antiretroviral therapy (cART). Little information to address this concern is available from clinical trials as patients with HCV are often excluded.

Aims

To compare incidence rates of discontinuation due to TOXPC associated with specific antiretrovial drugs in patients with or without HCV.

Patients/methods

A total of 4929 patients from EuroSIDA under follow-up from January 1999 on a specific nucleoside pair (zidovudine/lamivudine, didanosine/stavudine, stavudine/lamivudine, or other) with a third drug (abacavir, nelfinavir, indinavir, nevirapine, efavirenz, lopinavir/ ritonavir or other boosted-protease inhibitor (PI)-containing regimen) and with known HCV serostatus were studied for the incidence of discontinuation of any nucleoside pair or third drug due to TOXPC. Incidence rate ratios were derived from Poisson regression models.

Results

In total 1358 patients had HCV (27.5%). During 12 799 person-years of follow-up there were 2141 discontinuations due to TOXPC for nucleoside pairs and 2501 for third drugs. The incidence of discontinuation due to TOXPC was consistently higher in patients with HCV after stratification by nucleoside pair or third drug. After adjustment for CD4+ count, gender, exposure group, time on HAART, region and treatment regimen, there were few differences in the rate of discontinuation due to TOXPC in those with HCV compared with those without for any nucleoside pairs or third drugs. Similar results were seen when concentrating on discontinuation due to toxicities alone.

Conclusions

Although patients with HCV generally had higher rates of discontinuation due to TOXPC compared with patients without HCV, there was little evidence to suggest that this was associated with any specific nucleoside pair or third drug used as part of cART. Our results do not suggest that any specific component of cART is more poorly tolerated in patients with HCV or that the presence of HCV should influence the choice between antiretrovirals used as part of a cART regimen.