Title: Z Grossman
1Interpreting Resistance to Lopinavir/Ritonavir
in HIV-I Subtype C Patients
Z Grossman, D. Torten, E Shahar, I Levy, K
Risenberg, M Chowers, V Istomin, D Averbuch,
M Burke, E Mendelson, D Ram, S Maayan, M
Lorber, and JM Schapiro
Israels Multi-Center AIDS Study Group
National HIV Reference Laboratory, Central
Virology, PHL, MOH, Tel Aviv, Israel (Please see
appendix for the complete list of participating
investigators and centers)
INTRODUCTION
Resistance mutations conferring reduced
susceptibility and virological response to
lopinavir/ritonavir (LPV/RTV) are well
documented. A specific algorithm for predicting
LPV/RTV response is commonly used to interpret
resistance assay results and assist in
therapeutic decisions. The mutations included in
the algorithm were derived predominantly from
subtype B infected patients. The inclusion of
specific mutations in the algorithm is influenced
by both the magnitude of their effect and their
presence in the sample population studied.
Subtype-specific baseline prevalence of mutations
may influence drug specific mutational pathways
as well as affect the statistical derivation of
algorithms. We compared lopinavir/ritonavir
resistance in subtypes B and C infected patients.
In addition, we analyzed the outcome of LPV/RTV
treatment of B and non-B patients in Israel since
the introduction of the drug in 2001.
METHODS
Virological and clinical data from eight AIDS
clinics throughout Israel were collected in a
central database. Samples from infected patients
receiving LPV/RTV with HIV RNAgt1000 copies/ml
were analyzed. Population sequencing was
performed (TRUEGENE, Visible Genetics). Frequency
of individual mutations, calculated LPV/RTV
algorithm mutational scores, CD4 and HIV RNA
levels were collected. Results were compared with
subtype B data
RESULTS
No significant differences in HIV RNA, CD4
counts, age, treatment duration, drug usage and
toxicity between B C.