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Simplification from HAART to Kaletra Monotherapy: 2 pilot studies
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Reported by Jules Levin
"Simplification to Lopinavir/r single-drug HAART: 24 weeks results of a randomized, controlled, open label, pilot clinical trial (OK Study)"
In this poster presented by Jose Arribas from Spain, 42 patients had undectectable HIV RNA and were randomized to Kaletra monotherapy or Kaletra 3-drug HAART. There were 3 viral failures in the Kaletra patient group receiving Kaletra monotherapy vs none in those who continued on 3-drug HAART. All three patients restarted nucs & achieved undetectable HIV-RNA. Patients who were on Kaletra for longer duration before simplifying to monotherapy were more likely to stay undetectable & not to have viral rebound. Abbott is conducting larger international study to further explore the results from this pilot experimental study. Until we have further data these study results should be considered experimental. In this Abbott study they will examine body changes. My understanding is that DEXAs will be performed to evaluate if body abnormalities improve after switching to Kaletra monotherapy without nucs.
Arribas evaluated simplification of HAART to Lopinavir/r (Kaletra) single-drug HAART versus continuing Kaletra triple-drug HAART (2 nucs + L/r) in HIV-infected patients with suppressed HIV replication.
Patients were eligible if they had no history of virological failure while receiving a protease inhibitor (PI), were receiving 2 nucs + L/r (400 mg bid) for > 1 month and had maintained serum HIV RNA < 50 c/mL for > 6 months prior to enrolment.
Treatment failure was defined as: 2 HIV-RNA > 400 c/mL 2 weeks apart, change in randomized therapy, treatment discontinuation or lost to follow-up.
RESULTS
42 patients (86% male) were randomized (21 to Kaletra single-drug therapy and 21 Kaletra HAART 3-drug therapy). At baseline there were no significant differences between these two patient groups in median CD4 cells/mcL (662 vs 585), CD4 nadir (146 vs 145), HIV log10 viremia prior to HAART (5.11 vs 4.85) or months with HIV RNA < 50 c/mL (11 vs 9).
Nucs stopped in Kaletra single-drug therapy: AZT-3TC (33%), d4T-3TC (38%), other (29%). Nucs continued in Kaletra triple-drug HAART: AZT-3TC (43%), d4T-3TC (29%), other (28%).
Patients (%) with < 50/400 HIV RNA c/mL at 24 wk: 95/100% (Kaletra single-drug therapy) vs 100/100% (Kaletra 3-drug HAART) in the on-treatment analysis
….and 81/86% (Kaletra single-drug therapy) vs 100/100% (Kaletra 3-drug HAART) in the intention to treat (non completer = failure).
TREATMENT FAILURES
3/21 in Kaletra single-drug therapy group and 0/21 in Kaletra 3-drug HAART. All 3 patients had viral load reduced to undetectable after reintroduction of nucs into therapy.
Viral loads, genotyping at failure and results of reintroduction with previous nucs: 3,600 (week 12, after a 3-month period of 59% compliance; L63P present at rebound but also present in a pre-HAART sample, subsequently patient discontinued treatment), 1,270 (week 24, no mutations, results of reinduction pending) and 564 (week 24, no mutations, HIV-RNA < 50 c/mL after 4 weeks of reintroduction). Mean change in CD4 cells/mcL: +50 (Kaletra-sd) and +3 (Kaletratd).
Arribas concluded that, in contrast to previous trials of induction-manteinance strategy, a large proportion of patients simplified to Kaletra-sd remain with undetectable viral load after 24 weeks. Preliminary data show that failures of Kaletra-sd HAART are not associated with the development of resistance mutations.
"Maintenance therapy using Lopinavir/ritonovir (LPV/r) alone with well-controlled HIV Infection"
P. Ruane1, A. Luber, C. Gaultier, R. Stryker, D. Anderson, C. Peloquin, J. Rothbard. 1Tower ID Medical Associates, Los Angeles, United States; 2National Jewish, Denver, United States; 3Abbott Laboratories, Chicago, United States
Peter Ruane presented this poster at the Bangkok conference today & provided this background information. Prior experience with induction-maintenance strategies have shown poor outcomes. Maintenance with LPV/r alone may represent a viable option given its high potency, wide genetic barrier to resistance and tolerability. We evaluated LPV/r alone for maintenance therapy among patients with well-controlled HIV and no underlying protease (PR) resistance.
This study was a prospective, observational, one-site trial. Patients currently receiving HAART with non-detectable VL > 9 months and no evidence of PR resistance (by resistance testing and/or treatment history) were recruited.
Patients could be receiving LPV/r currently; if not, LPV/r was added to the regimen (400/100mg, 533/133 if HAART contains NNRTI). After 2 weeks of therapy, a trough LPV concentration was obtained; if greater than 3.0 ug/ml (2 standard deviations from median trough values in LPV/r PK studies), all agents except LPV/r were discontinued. Patients were evaluated bi-weekly for the first month and every month thereafter.
Primary end-points were time to virologic failure (2 consecutive VL > 400), proportion of patients who maintain non-detectable VL and CD4 cell count changes. Given varied times to follow-up, only those patients who met each time point were evaluated.
RESULTS
Four patients discontinued by week 8 & all had VL <75 copies/ml at last followup. Nineteen patients were enrolled (100% male). Median age, yrs HIV positive, and duration of prior HAART were 42 yrs, 5.5 yrs, and 34 weeks, respectively. Four patients were receiving LPV/r based HAART and 15 had LPV/r added; median trough concentration was 5.76 ug/ml.
| BL | Week 4 | Week 8 | Week 16 | Week 24 | | N=19 | n=19 | n=15 | n=15 | n=15 | | VL<400 | 100% | 100% | 100% | 100% | 100% | | VL<75 | 100% | 100% | 93%* | 92%† | 73%# | | CD4 | 628 | 602 | 736 | 682 | 634 |
*Pt 7-blip to 185, returned to <50 next visit;
†Pt 14-blip to 387, next visit 150;
#Pt 7- blip to 79, pt 10-blip to 327
Of the 15 patients who stayed in this study beyond week 8, 10 maintained VL <75 copies/ml and 5 patients had VL >75 copies/ml. Of these 5 patients, 3 had VL blips >75 but <400 copies/ml: 2 patients were said by Ruane to be non-adherent & 1 patient had lab error. Of the 2 patients with VL >400, Ruane said one patient was non-adherent and patient discontinued all ARVs at week 40. Second patient had 2300 copies/ml peak VL and genotype at week 40 was K20R & L63P, and phenotype showed pan-sensitivity to protease inhibitors.
MEDIAN CHANGES IN LIPIDS FROM BASELINE
| Wk 4 | Wk 8 | Wk 16 | Wk 24 | | N | 18 | 16 | 15 | 15 | | Chol | 2% | 10% | 10% | 7% | | LDL | 0% | 15% | 19% | 3% | | HDL | 3% | 16% | 17% | 5% | | TG | 41% | 58% | 65% | 90% |
Ruane concluded that maintenance therapy with LPV/r alone was well tolerated with continued viral suppression and immunologic benefit. Prospective, randomized studies that evaluate larger number of patients with longer duration of follow up are needed to validate these findings.
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