Treatment De-Intensification and Residual HIV-1 in Youth

Study Overview
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Brief Summary
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This laboratory-based sub-study of ATN 061 and ATN 071 will examine the effect of early treatment followed by treatment de-intensification to atazanavir/ritonavir (ATV/r) monotherapy on steady-state frequencies of replication-competent CD4+ T cell Human Immunodeficiency Virus (HIV)-1 reservoirs or cell-associated infectivity (CAI) and persistent low-level viremia (LLV), and their contribution to successful long-term control of HIV-1 replication among HIV-1 infected adolescents and young adults.

Official Title
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Treatment De-Intensification and Residual HIV-1 in Adolescents and Young Adults: A Sub-Study of ATN 061 and ATN 071.

Conditions
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HIV-1, HIV Infections

Intervention / Treatment
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* Other: Blood draw


Participation Criteria
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Eligibility Criteria
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081 participants must first be enrolled in either ATN 061 or ATN 071 and meet the eligibility criteria of those protocols in addition to those below. Inclusion Criteria: 061 Participants Currently on treatment with an ATV/r-based HAART regimen (ATV/r, FTC, TDF is the preferred regimen); HIV-1 viral load < 100 copies at week 24; CD4+ T cell count > 350 cells/mm3 at week 24; and Able to provide informed consent for the sub-study and adhere to the protocol. 071 Participants Initiated HAART according to current DHHS guidelines (CD4+ T cells < 350 cells/ mm3); Currently on treatment with a PI-containing HAART regimen; subjects taking a protease inhibitor OTHER than ATV/r must receive approval by the team via the ATN QNS; Plasma HIV-1 viral load < 100 copies at week 24 on HAART; measurement to be collected from clinical care results contained in the medical record at the clinical site within +/- 30 days of week 24 on therapy; CD4+ T cell count > 350 cells/mm3 at week 24 on HAART; measurement to be collected from clinical care results contained in the medical record at the clinical site within +/- 30 days of week 24 on therapy; and Able to provide informed consent for the sub-study and adhere to the protocol. General Exclusion Criteria: Currently enrolled in the Standard Care Arm of ATN 061; Pregnancy or breast feeding; Severe (Grade ≥ 3) anemia or other conditions that would not allow adequate blood volume to be drawn; Active treatment for systemic infections; Treatment with immune modulators, including immunosuppressive or immune modulating therapy (IL-2, intravenous gammaglobulin, and therapeutic or other experimental vaccines including HIV-1 vaccine given for primary prevention at any time (short courses (<14 days) of prednisone for reactive airway disease (RAD) are permitted); Active hepatitis B infection as defined by Hepatitis B antigen (Ag) positive; Disallowed Medications (see Section 5.3.2); Active drug or alcohol use or dependence that, in the opinion of the site personnel, would interfere with adherence to the study; or History of chronic renal insufficiency or Grade 3 or greater serum creatinine. 061-Specific Exclusion Criteria History of an Acquired Immunodeficiency Syndrome (AIDS)-defining illness; Meets any ATN 061 exclusion criteria for de-intensification; or Meets any ATN 061 premature study discontinuation criteria. 071-Specific Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 24 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 |
| --- | --- |
| Experimental<br>25 evaluable subjects from the experimental arm of ATN 061 who undergo de-intensification to boosted atazanavir (ATV) with VL suppression of < 100 copies/ml and CD4+ T cells > 350 cells/mm3 at week 48 and maintain VL suppression to < 400 copies/ml with stable CD4+ T cell counts after week 48. | Other: Blood draw<br>* This sub-study does not involve additional treatment of any ATN 061 or ATN 071 study subjects. The only intervention involved is the requirement for whole blood collection (40 ml and 60 ml) to be drawn at the same time as four ATN 061 study visits (36, 48, 56, and 80 weeks) for subjects co-enrolled into ATN 061. When these time points coincide with ATN 061 Central Laboratory samples, the 60 ml blood sample will not be collected. For subjects co-enrolled into ATN 071, there are also two samples of whole blood collection (40 ml and 60 ml) required to be drawn at four time points but at weeks 36, 48, 56, and 80 after the initiation of HAART.<br>|
| Control<br>25 evaluable subjects from ATN 071 will also be enrolled. These subjects will have initiated HAART according to current DHHS guidelines (CD4+ T cells < 350 cells/mm3), had viral load suppression to < 100 copies/ml at 24 through 48 weeks on HAART and maintained suppression to < 400 copies/ml through week 80. | Other: Blood draw<br>* This sub-study does not involve additional treatment of any ATN 061 or ATN 071 study subjects. The only intervention involved is the requirement for whole blood collection (40 ml and 60 ml) to be drawn at the same time as four ATN 061 study visits (36, 48, 56, and 80 weeks) for subjects co-enrolled into ATN 061. When these time points coincide with ATN 061 Central Laboratory samples, the 60 ml blood sample will not be collected. For subjects co-enrolled into ATN 071, there are also two samples of whole blood collection (40 ml and 60 ml) required to be drawn at four time points but at weeks 36, 48, 56, and 80 after the initiation of HAART.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady-state frequencies of replication-competent CD4+ T cell HIV-1 reservoirs in participants starting HAART before DHHS guidelines (CD4+ T cell levels < 350 cells/mm3) vs. those initiating HAART by current DHHS guidelines. |  | 80 weeks | 
| Quantitative changes in LLV between 6.5 and 50 copies/ml in participants starting early therapy & de-intensifying to ATV/r monotherapy vs. those initiating HAART at CD4+ T cell levels < 350 cells/mm3 & maintaining standard HAART. |  | 80 weeks | 
| Quantitative changes in viral diversity during HAART in participants initiating early therapy & de-intensifying to ATV/r monotherapy vs those initiating HAART at CD4+ T cell levels < 350 cells/mm3 & maintaining standard HAART. |  | 80 weeks | 
| Effect of viral diversity in replication-competent CD4+ T cell reservoirs & low viremia variants before de-intensification on successful control of HIV-1 replication during ATV/r maintenance in participants starting HAART before DHHS guidelines. |  | 80 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the contribution of LLV genotypes, through analysis of the Gag/protease and RT, among subjects who developed rebound viremia above 50 copies/ml during treatment de-intensification to ATV/r. |  | 80 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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de-intensification, HAART, monotherapy, persistent low-level viremia (LLV), treatment experienced