Use of lopinavir/ritonavir in HIV-infected patients failing a first-line protease-inhibitor-containing HAART.
OBJECTIVE
The long-term virological efficacy of lopinavir/ritonavir-containing highly active antiretroviral therapy (HAART) in HIV-infected patients failing a first-line protease inhibitor (PI)-based regimen is still unclear.


METHODS
An observational study was carried out from December 2000-December 2002 on 111 consecutive patients starting lopinavir/ritonavir. The primary end-point was virological success (HIV RNA <50 copies/mL in two consecutive determinations). CD4 outcome, lipid levels and adverse events were recorded. The Kaplan-Meier method and log-rank test were used to estimate the time-dependent probability of reaching the end-point using intention-to-treat and on-treatment approaches.


RESULTS
Ninety-six patients obtained virological success during follow-up; Kaplan-Meier analysis showed that the time-dependent probability of obtaining this end-point was 78.4% at month 12 and 85.8% at month 24. The median CD4+cell count increased by 118 cells/mm(3) from baseline to month 12 and by 153 cells/mm(3) to month 24. Thirty-one patients discontinued lopinavir/ritonavir: 16 because of drug-related toxicities, six for simplification, five because of virological failure, one patient was lost at follow-up and three died. An elevation in lipid parameters was observed, but only a minority of patients developed a grade 3 or higher hypertriglyceridaemia and/or hypercholesterolaemia. Among the 15 patients not reaching virological success, five had < or =5 mutations in the protease region known to reduce susceptibility to lopinavir/ritonavir (one discontinued lopinavir/ritonavir because of gastrointestinal intolerance), five had no mutations (two discontinued lopinavir/ritonavir because of gastrointestinal intolerance) and five showed > or =6 mutations (all discontinued lopinavir/ritonavir); however, of the patients who discontinued lopinavir/ritonavir none achieved HIV RNA <50 copies/mL on subsequent regimens.


CONCLUSIONS
Lopinavir/ritonavir was highly effective and well tolerated in HIV-infected patients failing a first-line PI-based HAART.
Bongiovanni
Marco
M
Institute of Infectious and Tropical Diseases, Ospedale Luigi Sacco, University of Milan, Via G.B. Grassi 74, 20157 Milano, Italy. marco.bongiovanni@unimi.it
Chiesa
Elisabetta
E
Di Biagio
Antonio
A
Meraviglia
Paola
P
Capetti
Amedeo
A
Tordato
Federica
F
Cicconi
Paola
P
Biasi
Patrizia
P
Bini
Teresa
T
d'Arminio Monforte
Antonella
A
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir