Effectiveness Study Low-Dose Naltrexone Versus ARV's for HIV+

Study Overview
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Brief Summary
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In the vast majority of those infected with HIV virus who are untreated, there is deterioration in immune health over a period of months or years inevitably leading to full-blown AIDS and demise. Treatment with ARV's stop or slow down this deterioration if started before a certain degree of progression occurs and has saved millions of lives. The investigators' study hypothesis is that effectiveness of a very low dose of an FDA-approved medication, naltrexone hydrochloride, (Low-Dose Naltrexone, or LDN) will compare favorably to ARV's to prevent progression of HIV+ toward immune deterioration and full-blown AIDS.

Detailed Description
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The LDN (low-dose naltrexone) vs ARV (anti-retroviral drugs) Effectiveness Study in Mali sponsored by The Ojai Foundation in California-USA is a clinical research study endorsed and approved by the Malian Government. Naltrexone hydrochloride is a generic, FDA-approved since 1998 drug, an opioid antagonist that has clinically shown immune enhancing/modulating qualities in very low dosage and may offer an alternative to ARV drugs that is effective, non-toxic, easily available, inexpensive, with simple once-daily at bedtime administration. LDN capsules must be created by compounding pharmacists to get these ultra-small doses. Due to toxicity of current ARV drugs and need for special medical management young HIV infected children are largely neglected particularly in developing countries; LDN can also be made available in a transdermal cream for infants and children who are HIV infected.

Official Title
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Phase 2 Comparison of Low-Dose Naltrexone vs ARV Effectiveness in HIV+ Progression

Conditions
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HIV Seropositivity

Intervention / Treatment
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* Other: ARV's + Placebo
* Drug: Naltrexone
* Drug: Naltrexone + ARV's


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected CD4 count over 350 (arm 1/group 1) CD4 count over 200 and on ARV's (arms 2,3/groups 2,3) Age between 18 & 60 Males or females Exclusion criteria: HIV-1 seronegative HIV-2 infected CD4 count lower than 200 patients under age 18 Those refusing to be in study Pregnant or breast-feeding women Patients under immuno-suppressor therapy Those with renal or hepatic dysfunction Malaria or tuberculosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Experimental: Naltrexone Low-dose 3mg capsule<br>Each person in this arm 1 of the study had never received any ARV drugs and in this study received only one Low-Dose Naltrexone 3mg capsule nightly for 9 months (no placebo). | Drug: Naltrexone<br>* Naltrexone, Low-Dose (3mg) given once daily at bedtime for 9 months<br>|
| Active Comparator: Naltrexone Low Dose + ARVs<br>In this Arm 3, Patients were on ARV's plus being given Naltrexone Low-Dose (3mg) once daily at bedtime for 9 months. | Drug: Naltrexone + ARV's<br>* Patients were given standard ARV's plus Naltrexone (Low Dose) 3mg nightly.<br>* Other names: Emtricitabine + tenofovir + efavirenz;|
| Placebo Comparator: ARV's (continued,standard) plus Placebo<br>In this arm 2, patients were started or continued on their standard ARV drugs plus placebo capsule once daily at bedtime; in the 2nd and 3rd arms patients did not know whether they were taking Low-Dose Naltrexone or a placebo. | Other: ARV's + Placebo<br>* Patients continued ARV's plus a placebo nightly for 9 months<br>* Other names: Emtricitabine + tenofovir + efavirenz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ percentage (change in HIV-1 seropositive patients) | HIV+ patients with CD4+ count over 350 had their CD4 count/percentage measured at beginning, at 15 days, at 1 month, 3 months, 6 months and 9 months (end). | 9 MONTHS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical assessment of evidence of AIDS or other serious illness | HIV+ patients with CD4 counts over 200 on ARV drugs were given clinical assessment and testing for evidence of opportunistic infections (AIDS) at each visit for blood testing: (Beginning, 15 days, 1 month, 3 months, 6 months, & 9 months (end). | 9 MONTHS |