"OK 2004 Study" (Only Kaletra 2004 Study): Study to Evaluate Suspending Nucleosides From Triple-Drug Therapy in HIV Subjects

Arribas, Jose R., M.D.

Status and phase

Completed

Phase 4

Conditions

HIV Infection

Treatments

Drug: Stopping nucleosides and continuing lopinavir/ritonavir monotherapy

Study type

Interventional

Funder types

Industry

Identifiers

NCT00114933

EudraCT 2004-001323-37

SPA-378-05-40

Details and patient eligibility

About

Lopinavir/ritonavir monotherapy may maintain virologic suppression in patients who have been undetectable for six months while on triple drug antiretroviral therapy. Lopinavir/ritonavir pharmacokinetics might prevent resistance development in patients who experience virological rebound after single-drug simplification.

Full description

Primary Study Objective: Efficacy and durability of switching to lopinavir/ritonavir single-drug HAART compared to maintaining therapy based on lopinavir/ritonavir and two nucleosides

Secondary Study Objective(s):

Safety (related drug AEs/SAEs and laboratory anomalies G3/4) through 48 w.
Resistance profile on patients with sustained virological failure
QOL comparing stopping nucleosides versus continuing therapy
Pharmaco-economic analysis comparing treatment cost between the 2 study arms.
Predicting factors of failure in the stopping nucleosides arm

Subject Population: 200 patients

Study Design:

RANDOMIZATION:

Patients are randomized (1:1) either to continue under the same treatment or stop nucleosides as follows:

Stopping nucleosides arm: Lopinavir/r alone.
Continuing arm: Lopinavir/r + 2 NRTIs

STUDY PROCEDURES: A baseline HIV-RNA, CD4 and routine labs will be collected if the most recent results are not collected within the 4 weeks prior entering the study. Patients will be followed for HIV-RNA (and CD4) at w1, w4, w8, w16, w24, w 36 and w48. After w48, durability of response to lopinavir/r single-drug therapy will be studied long-term (up to w96). Routine hematology and clinical chemistry (including fasting triglycerides and cholesterol, total and HDL/LDL ratio) will be measured at w4, w16, w24, w 36 and w48. A central laboratory will be used for HIV-RNA determinations and to archive plasma/cell samples for further genotype test in case of rebound.

Treatment adherence will be followed with a self-patient report questionnaire (GEEMA study)

All AEs will be collected if suspected relation (possible or probable) to any concomitant ARV drug, and SAEs, related or not, reported within 24h.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

HIV patients > 18 years old who provide signed and dated Informed consent.
HIV patients who have been receiving lopinavir/ritonavir and two nucleosides during at least 4 weeks.
Plasma HIV RNA < 50 cop/ml for six months

Exclusion criteria

HIV patients who have stopped a protease inhibitor due to virological failure.
HIV patients with hepatic or renal insufficiency.
HIV patients with positive serum HBVAg
HIV patients who require treatment with a lopinavir/r contraindicated medication.
HIV pregnant or breastfeeding women.
Active drug abuse (including alcohol or recreational drugs). Exception, cannabis, provided the investigator is confident in patient adherence. Patients under Methadone program will be accepted too if deemed appropriate by the investigator.