Kaletra Monotherapy A RealLife Experience Laura Waters Steve

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Kaletra Monotherapy: A Real-Life Experience Laura Waters, Steve Balbeck, Brian Gazzard & Mark Nelson.

Kaletra Monotherapy: A Real-Life Experience Laura Waters, Steve Balbeck, Brian Gazzard & Mark Nelson. St Stephen’s Centre, Chelsea & Westminster Hospital, United Kingdom INTRODUCTION Since the introduction of HAART the increasing recognition of drug-related toxicities and the development of more potent antivirals have stimulated exploration of alternative regimens and strategies for experienced patients including protease inhibitor (PI) monotherapy. Limited data supporting the use of boosted lopinavir (LPV/r) as a single agent (unlicensed) has been presented (refs) and larger trials are ongoing. We have a number of patients at our unit who have been prescribed LPV/r therapy outside a trial protocol. Virological Outcomes: log changes Of the 15 individuals with viraemia at the time of switch to LPV/r monotherapy 11/15 (73%) achieved a greater than 1 log reduction in viral load. Immunological Outcomes The overall CD 4 gain in the 28 individuals with follow-up was 92 cells/mm 3 (232 to 324) after a mean of 8. 9 months. CD 4 changes in the group achieving undetectability are summarised in table 2. Table 2: CD 4 change up to 1 year (on treatment; virologically suppressed). METHODS Using our large, prospective database all individuals who have ever received LPV/r monotherapy up until October 2005 were identified; all those taking part in a clinical trial were excluded. Previous treatment history, resistance and reason for switch were defined and CD 4, viral load (VL), alanine transaminase (ALT), total cholesterol (TC) and triglygeride (TG) levels were monitored for up to 12 months. RESULTS 12 353 238 +81 9 225 141 +25 5 333 218 +57 7 318 193 +115 Month 3 Month 6 Month 9 Month 12 13 221 188 +36 10 293 234 +70 9 287 249 +64 9 209 247 +73 Treatment Failure The 8/28 subjects with follow-up who changed or stopped therapy are described below. Table 4: Subjects switching therapy. Subject 19 switched to LPV/r for adherence difficulties, 4 secondary to drug-related toxicity, 1 due to drug interaction and 1 patient request. Reasons were not documented for 10 subjects. - 2 treatment interruption (prescribed LPV/r to cover NNRTI cessation) - 3 lost to follow-up - 2 for toxicity (1 gastrointestinal, 1 transaminitis ? cause) Month 12 Number patients Mean CD 4 (cells/mm 3) SD(+/-) Change from baseline Reasons for switch 7 individuals had no post-baseline results available for the following reasons: Month 9 CD 4 rises in those who did notreceive a viral load less than 50 copies/ml are demonstrated in table 3 Table 3: CD 4 change up to 1 year (on treatment; detectable viraemia). Table 1: Baseline Characteristics 43 (29 -63) 248 (1 -573) 54, 866 (<50 ->500, 000) 0 (0 -4) 2 (0 -5) 5 (1 -12) 139 (84) 23 (46) 14 (15) 15 (20) Month 6 Number patients Mean CD 4 (cells/mm 3) SD(+/-) Change from baseline 35 individuals, 8 women and 27 men, received LPV/r monotherapy; baseline characteristics are illustrated in table 1. Age (years); mean (range) CD 4 (cells/mm 3); mean (range) Viral load (copies/ml); mean (range) Number major PI mutations; median (range) Number minor PI mutations; median (range) No. previous regimens; median (range) Months NRTI exposure; mean (SD) Months NNRTI exposure; mean (SD) Months boosted PI exposure; mean (SD) Months unboosted PI exposure; mean (SD) Month 3 Outcome 1 Intensified with TFV/FTC at 1 year (no CD 4/VL response) 2 3 4 5 6 7 8 Added TFV/3 TC when undetectable, reason unclear Undetectable at 18 months, TFV added for blips dd. I added at 2 months, undetectable (reason unclear) Intensified with ABC/3 TC at 1 year (no CD 4 response) Switched to salvage; later died MAI; VL 150, 000 at 1 year Switched TFV/FTC/ATV/r, <50 CD 4 662 12/05 VL 69 at 1 year on LPV/r; switched to ABC/TFV/ATV/r <50 after 1 year Baseline Resistance 7 patients had a history of major PI mutations (defined as per IAS guidelines); 1 was lost to follow-up and 1 received 3 weeks of LPV/r only, the remaining 5 are described in Table 5: Treatment outcomes in subjects with major PI mutations. Virological Outcomes: Undetectability 14/28 (50%) achieved an undetectable viral load within 12 months (mean followup 9. 2 +/-3. 9 months); 10/14 had an undetectable viral load at baseline (and 8/10 of these simplified a LPV-based regimen). 11/14 remain on LPV/r monotherapy and 10/11 have viral load <50 copies/ml at a mean of 12. 1 months (range 3 -34); 1 subject had a viral load of 129 copies/ml at 20 months. 3/14 changed therapy, 1 added tenofovir for blips, 1 added didanosine and 1 added two nucleosides (reasons unclear). 14/28 did not achieve an undetectable viral load within 12 months, 3 of whom were undetectable at baseline (2 on a LPV-containing regimen). 9/14 remain on LPV/r monotherapy; 7/9 have a viral load less than 400 copies/ml out to 1 year (mean 10 months). 1 has viral load of 1494 copies/ml at 12 months (baseline 57693; 1. 5 log drop) and 1 has a viral load at 1878 copies/ml (from >500, 000 copies/ml; >2. 4 log decline) at 3 months. With prolonged follow-up 2 are now undetectable after 16 and 24 months respectively. Of the other 5 subjects, 1 was switched to salvage therapy and subsequently died, 2 were intensified with 2 nucleosides (results pending) and 2 switched to atazanavir-based HAART and achieved viral loads <50 copies/ml. No. Switch From Major Mutations VL t 0 CD 4 change Outcome 1 LPV, TFV D 30 N 50 446 +188 Continues; VL <400 at 1 year 2 LPV, TFV, ABC 32 I, 46 I, 82 A 50 443 -42 Continues; VL <50 at 6/12 3 TFV, dd. I, NVP 46 I, 50 V, 90 M 1484 103 +89 Continues; VL <50 at 1 year 4 AZT, 3 TC, ABC, TFV 46 I, 54 L, 84 V, 90 M 50993 8 -2 No CD 4/VL response 1 year; TFV/FTC added (result awaited) 5 LPV, SQV 84 V 58280 32 -15 Minimal response 1 year; poor compliance + New Resistance 10 patients with viraemia underwent genotyping on LPV/r monotherapy. 4/10 didn’t amplify, 2/10 had no resistance test recently prior to LPV/r for comparison, 1/10 exhibited no new mutations, 2/10 developed new minor mutations/polymorphisms (63 P and 63 P/79 A/93 L respectively) and 1/10 developed 20 R/46 I/50 V. CONCLUSIONS 35 subjects in our cohort were prescribed LPV/r monotherapy and we present outcomes for 28. 2 individuals switched primarily for toxicity however, the impact of adverse events on compliance and subsequent failure could not be elucidated fully from a retrospective note review. The majority of patients were switched to LPV/r for poor compliance and all were treatment experienced. 50% achieved an undetectable viral load (less than 50 copies/ml) and the majority attained a greater than 1 log reduction in viral load, an independent prognostic factor. The majority of subjects experienced a CD 4 increase. LPV/r therapy provided a safe, effective treatment option in a highly experienced group of poorly compliant individuals.