HIV-1 Envelope Sequence Diversity Within the Latent Reservoir in HIV-1 Infected Individuals Initiated on Antiretroviral Therapy (ART) During Acute and Chronic Infection.
- Conditions
- HIV-1Human immunodeficiency virus type-11004743810021460
- Registration Number
- NL-OMON47974
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
• Ages >= 18 years of age
• Ability and willingness to provide informed consent
• Clinically stable on ART without changes in ARV status in the 24 weeks prior to screening. A change in ART >= 60 days prior to study visit for reasons other than virologic failure (eg, tolerability, simplification, drug-drug interaction profile) is allowed
• Plasma HIV-1 RNA plasma levels < 50 copies/mL at screening
• At least two documented HIV-1 RNA plasma levels < 50 copies/mL within the last 24 weeks (may include screening HIV-1 RNA plasma level). Results must come from a licensed assay with a lower limit of quantification of <50 copies/mL
o Unconfirmed virologic elevations of >= 50 copies/mL (transient detectable viremia, or *blip*) >= 12 weeks prior to screening are acceptable. If the lower limit of detection of the local HIV-1 RNA assay is <50 copies/mL, the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests
• Have an absolute neutrophil count >= 1500 cell/mm3, platelets >= 150,000/mm3; hemoglobin (Hgb) >= 11.5g/dL (females) or >= 13g/dL (Males)
• Have a creatinine clearance (CLcr) >=70 mL/min ( >=90 mL/min for leukapharesis subjects only) (using the Cockcroft-Gault method {Cockcroft 1976} based on serum creatinine and actual body weight as measured at screening
• Ionized calcium level of >=1.1 mmol/L (4.4 mg/dL), serum Mg >= 1.6 mg/dL (for subjects undergoing leukapharesis only)
• Have liver function tests such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin normal or below the upper limit of normal at screening
• Prothrombin Time (PT) < 1 × Upper Limit of Normal (ULN), International Normalized Ratio of prothrombin time (INR) <1.1 × ULN and Activated Partial Thromboplastin Time (APTT) < 1 × ULN
• Available documented baseline demographic and clinical data
• Positive urine pregnancy test
• Subjects weighing less than 110 lbs
• Subjects who have donated more than 400 ml of blood within 56 days of Day 1
• For subjects undergoing leukapheresis, known allergic reactions to any component(s) of leukapheresis (e.g., citrate, heparin etc)
• History of opportunistic illness indicative of stage 3 HIV
• Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with subject assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders other than HIV-1 infection, active infection, or malignancy that are clinically significant or requiring treatment.
• Have been treated with systemic steroids, immunosuppressant therapies, immunomodulatory therapies, chemotherapeutic agents within 3 months prior to enrollment.
• Acute or chronic bleeding disorder or use of blood thinners within 2 weeks of Day 1
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine the frequency of R5-tropic N332+ viral isolates present within the<br /><br>latent reservoir while on suppressive ART.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- To determine the frequency of R5-tropic N332+ viral isolates present in<br /><br>plasma prior to ART initiation.<br /><br>- To evaluate HIV-1 envelope diversity prior to initiation of ART in plasma and<br /><br>within the latent reservoir in ART suppressed individuals who initiated ART in<br /><br>acute (including hyperacute infection [Fiebig I & II]) versus chronic infection.<br /><br>- To compare neutralization sensitivity to GS-9722 and other HIV-1 broadly<br /><br>neutralizing antibodies of replication competent reservoir virus isolates from<br /><br>ART suppressed individuals who initiated ART in acute versus chronic infection.<br /><br>- To compare the size of latent reservoir in peripheral blood mononuclear cells<br /><br>(PBMCs) of individuals initiated on ART in acute versus chronic HIV-1 infection<br /><br>following long-term suppressive ART.</p><br>