Discontinuation of Primary and Secondary Prophylaxis for Opportunistic Infections in HIV-infected Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare the incidence of opportunistic infections between HIV-infected patients who continue and discontinue primary or secondary prophylaxis for opportunistic infections in whom receiving combination antiretroviral therapy and achieve undetectable HIV-1 RNA, but CD4 cell counts are less than 200 cells/mm3.

Detailed Description
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Currently, combination antiretroviral therapy (cART) has become the standard of care in the treatment of HIV infection in many parts of the world including Thailand. The benefits of cART represented by an increment of CD4 cell count and a suppression of HIV viral load have been reported worldwide. The National Institute of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA) recommended discontinuing primary and secondary prophylaxis for prevention of opportunistic infections (OIs) in HIV-infected adults and adolescents receiving cART, when the CD4 cell count increase to a certain level for a certain period of time. For instances, Pneumocystis jiroveci pneumonia (PCP) prophylaxis can be discontinued when patients receiving HAART and CD4 ≥ 200 cells/mm3 for at least 3 months (for primary prophylaxis) or at least 6 months (for secondary prophylaxis), prophylaxis for Cryptococcal meningitis, disseminated penicilliosis, cerebral toxoplasmosis, and disseminated mycobacterium avium complex can be discontinued when patients receiving HAART and CD4 ≥ 100 cells/mm3 for at least 6 months. Our practices follow this guideline. However, recently there are new data showing that there were no cases developed PCP after primary or secondary prophylaxis discontinuation even if CD4 cell count < 200 cells/mm3. Discontinuation of secondary prophylaxis resulted in reduction in pill burdens that may improve HAART adherence, decrease drug-drug interactions, and also prevent drug adverse events that may happen.

Official Title
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Discontinuation of Primary and Secondary Prophylaxis for Opportunistic Infections in HIV-infected Patients Who Had CD4+ Cell Count <200 Cells/mm3 But Undetectable Plasma HIV-1 RNA

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Discontinuation of prophylactic drugs i.e. co-trimoxazole, dapsone, fluconazole, itraconazole, azithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old regularly receiving highly active antiretroviral therapy (HAART) during follow up CD4 cell count < 200 cells/mm3 HIV-1 RNA < 50 copies/ml after receiving HAART receiving primary or secondary prophylaxis for opportunistic infections including infections caused by Pneumocystis jiroveci, Cryptococcus neoformans, Penicilliosis marneffei, Histoplasma capsulatum, Toxoplasma gondii, Mycobacterium avium complex given written informed consent Exclusion Criteria: 1) pregnancy

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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm A<br>Continuation of prophylaxis of opportunistic infections | |
| Experimental: Arm B<br>Discontinuation of opportunistic infections | Other: Discontinuation of prophylactic drugs i.e. co-trimoxazole, dapsone, fluconazole, itraconazole, azithromycin<br>* Discontinuation of prophylaxis for opportunistic infections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of opportunistic infections | To test whether the incidence of opportunistic infections differs between these 2 groups Patients receiving cART and discontinue primary or secondary prophylaxis if their HIV-1 RNA achieve undetectable level. Patients receiving cART and continue primary or secondary prophylaxis even if HIV-1 RNA achieve undetectable level. | Participants will be followed up to 135 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary prophylaxis, Secondary prophylaxis, Discontinuation