Clinical, Virological and Safety Outcomes of a Lopinavir/Ritonavir-Based Regimen in HIV-1 Infected Patients in Routine Clinical Use in China

Study Overview
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Brief Summary
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This post-marketing observational study is conducted for obtaining data on clinical, biological and virological outcomes, compliance and tolerability of using a lopinavir/ritonavir (LPV/r) -containing regimen for the treatment of naïve or experienced patients infected with human immunodeficiency virus type 1 (HIV-1) in China. Although LPV/r is frequently used world-wide, the evaluation of the outcomes, compliance, and tolerance of anti-HIV strategies in real life is still a major challenge in the management of HIV-infected patients who are on a life-long therapy, especially in China. This study will help to develop effectiveness and safety profile of the lopinavir/ritonavir containing regimen in Chinese HIV-1 infected patients, provide more choices of anti-HIV-1 strategies to Chinese experts and benefits Chinese HIV-1 infected patients.

Detailed Description
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It is planned to enroll approximately 100 patients in total. This will be a multicenter post-marketing observational study in China mainland. Each patient will be observed during his/her lopinavir/ritonavir - containing treatment regimen for a maximum period of 18 months. If the physician decides to permanently discontinue lopinavir/ritonavir before the end of the planned observational period of 18 months, the reason for the discontinuation and the new treatment regimen prescribed will be documented. The next routine follow-up visit will be the termination visit for this patient in this study. This post-marketing observational study will be conducted in a prospective, single-arm, multicenter format. As this study is observational in nature, its follow-up is not interventional and is left to the judgment of each physician within the 18-month period, which defines the survey for each patient. For indicative purpose, follow-up of patients should enable approximately 4 patient visits during this period. These visits will take place at average intervals of 6 months, apart from the first visit following inclusion (usually at the end of the first 3 treatment months) and apart from visits required because of an intercurrent event. If treatment with lopinavir/ritonavir is discontinued, standard practice is to review the patient after a period of 3 months. For these reasons, the most likely visits are defined as V1, V2, V3, V4 although numbers and dates will depend only on the decision of the physician. As a result, failure to meet these suggested dates will not constitute a deviation of the protocol.

Official Title
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Clinical, Virological and Safety Outcomes of a Lopinavir/Ritonavir-Based Regimen in HIV-1 Infected Patients in Routine Clinical Use in China: A Multicenter Post-Marketing Observational Study

Conditions
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HIV-1 Infections

Intervention / Treatment
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* Drug: Lopinavir/ritonavir (Kaletra)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients infected by HIV-1 who are over 18 years old Patients who belong to one of the following cohorts: Antiretroviral naïve patients Antiretroviral experienced patients, irrespective to their immune and viral status and current antiretroviral therapy Exclusion Criteria: Patients who have been treated with lopinavir/ritonavir Patients who are being treated or will be treated with drugs at risk of interactions with lopinavir/ritonavir Patients who are not tolerant to lopinavir/ritonavir Patients who have uncontrolled AIDS defining disease Patients participating in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lopinavir/ritonavir group<br>This study is a non-interventional, observational study in which lopinavir/ritonavir is prescribed in the usual manner in accordance with the terms of China market authorization with regards to dose, population and indication. It is planned to enroll approximately 100 patients in total. | Drug: Lopinavir/ritonavir (Kaletra)<br>* Lopinavir/ritonavir(LPV/r) is an HIV protease inhibitor (PI) that is co-formulated with lopinavir and ritonavir. Lopinavir is an inhibitor of the HIV-1 and HIV-2 proteases. As co-formulated in LPV/r, ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir. The assignment of the patient to a lopinavir/ritonavir - containing regimen is not decided in advance by this protocol but falls within current practice and the prescription of lopinavir/ritonavir is clearly separated from the decision to include the patient in this study.<br>* Other names: Kaletra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the HIV Viral Response | The protocol recommended that HIV viral load tests be performed at baseline and each study visit. Test results indicate the number of HIV-1 ribonucleic acid (RNA) copies per milliliter (mL). The number of participants who underwent testing and had detectable levels (greater than 50 copies/mL) or undetectable levels (less than 50 copies/mL) are presented by subgroup. Study visits were to occur at approximately 3, 6, 12, and 18 months after starting treatment. The exact dates of each visit depended on the physician's judgment, so data are reported for Visits 1 through 4 rather than by month. | Month 3, 6, 12, 18 | 
| Evolution of CD4 Count | The evolution of participants' CD4-positive (CD4+) T-lymphocyte counts after starting the lopinavir/ritonavir-containing regimen was to be assessed by measuring the number of CD4+ cells at baseline and each subsequent study visit. CD4+ count results are reported as the number of CD4+ cells per cubic millimeter (cmm). Study visits were to occur at approximately 3, 6, 12, and 18 months after starting treatment. The exact dates of each visit depended on the physician's judgment, so data are reported for Visits 1 through 4 rather than by month. | Month 3, 6, 12, 18 | 
| Evolution of the Tolerance Issues | At each study visit, treating physicians evaluated participants and used their clinical judgment to determine if they were tolerating the lopinavir/ritonavir-containing regimen. Study visits were to occur at approximately 3, 6, 12, and 18 months after starting treatment. The exact dates of each visit depended on the physician's judgment, so data are reported for Visits 1 through 4 rather than by month. | Month 3, 6, 12, 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Missed Doses, Interrupt or Discontinue Regimen, and Experience Changes in Dosage or of Combination Regimen | Visits were to occur at approximately 3, 6, 12, and 18 months after starting treatment. The frequency with which each participant forgot to take their medication since the last visit and discontinuations of treatment and the reasons were documented at each visit and are summarized. The number of participants changing from lopinavir/ritonavir soft gel capsule to tablet are also presented. The exact dates of each visit depended on the physician's judgment, so data are reported for Visits 1 through 4 rather than by month. Note: participants may have had multiple missed doses or therapy changes. | Month 3, 6, 12, 18 | 
| Adverse Events Observed and Development of Lipodystrophy Lesion and Their Locations | The types of adverse events reported are summarized. The presence of lipodystrophy (abnormal body fat distribution) and its location was to be recorded. However, due to an oversight, there was not a place to record the location of lipodystrophy on the case report form. Doctors used clinical judgment to rate lipodystrophy in treatment-experienced participants. Study visits were to occur at approximately 3, 6, 12, and 18 months after starting treatment. The exact dates of each visit depended on the physician's judgment, so data are reported for Visits 1 through 4 rather than by month. | Month 3, 6, 12, 18 | 
| The Duration on Treatment Until Development of an Adverse Event Leading to Treatment Discontinuation or Until Escape From Treatment | As so few participants withdrew from lopinavir/ritonavir treatment, durations of lopinavir/ritonavir therapy required for 25 percent, 50 percent and 75 percent of participants could not be established. The numbers of participants in each subgroup who discontinued from treatment due to an adverse event are presented. | Month 3, 6, 12, 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lopinavir/ritonavir